Featured are articles on sibutramine and cardiovascular outcomes in overweight and obese subjects, intensive blood-pressure control in hypertensive chronic kidney disease, dose comparisons of clopidogrel and aspirin in acute coronary syndromes, chemotherapy or surgery in ovarian cancer, and disclosure of large-scale adverse events; a review article on calcium kidney stones; a Clinical Problem-Solving article on a woman originally from Nepal who presented to her physician after unsuccessful attempts at pregnancy for 18 months; and Perspective articles on walking the tightrope of health insurance reform between 2010 and 2014, on insurance-premium rates and the ACA, and on indoor tanning.

This article is from the issue dated September 2, 2010. In this clinical trial, the appetite suppressant sibutramine as compared with placebo resulted in modest weight loss but also in an unexpected increase in the risk of nonfatal myocardial infarction and stroke (a finding limited to patients with preexisting cardiovascular disease).

This Editorial is from the issue dated September 2, 2010. On September 15, 2010, an advisory committee of the Food and Drug Administration (FDA) will meet to determine the fate of sibutramine, an appetite-suppressant drug that carries the brand name Meridia.

Also, the Images in Clinical Medicine feature is described.

This article and related Editorial are from the issue dated September 2, 2010. This trial tested whether intensive blood-pressure control retards the progression of chronic kidney disease in black patients with hypertension.

This article is from the issue dated September 2, 2010. Some adverse events such as a failure to disinfect medical equipment have the potential to harm many patients. The authors argue that medical institutions should develop policies for addressing large-scale adverse events and should routinely disclose these events to patients, even when the risk of harm is very low.

This article is from the issue dated September 2, 2010. Both political parties wax poetic about the need for popular insurance reforms, but legislating what is necessary and implementing it properly has always been the trick.

This article is from the issue dated September 2, 2010. An estimated 1 million times per day, someone in the United States uses ultraviolet (UV) radiation for skin tanning.

This article is from the issue dated September 2, 2010. Over the past decade, the largest health insurance companies have seen a disproportionate increase in profits of 250%, or 10 times the rate of inflation. During the past year alone, there has been a double-digit increase in health insurance premiums.

This summary covers the issue of August 26, 2010. Featured are articles on inhibition of mutated, activated BRAF in metastatic melanoma, sirolimus and kidney growth in autosomal dominant polycystic kidney disease, everolimus in patients with autosomal dominant polycystic kidney disease, underinsurance among children in the United States, and cancer and caprice; a review article on new therapeutic approaches to mendelian disorders; a case report of a man with loss of vision and a rash; and Perspective articles on treating cancer and guidelines for low-income countries, on revisiting the rosiglitazone story, and on the reality of drug shortages and the case of the injectable agent propofol.

This article summary is from the issue dated August 26, 2010. Many melanomas contain an activating mutation in BRAF: a substitution of glutamic acid for valine at amino acid 600 (the V600E mutation). The authors conducted a two-phase study to describe the activity of a new agent, PLX4032, that inhibits mutated BRAF.

This article is from the issue dated August 26, 2010. In July 2007, 24 members of the Endocrinologic and Metabolic Drug Advisory Committee and the Drug Safety and Risk Management Advisory Committee of the Food and Drug Administration held a joint meeting and concluded that rosiglitazone, an insulin-sensitizing agent used in treating type 2 diabetes mellitus, was associated with an increased risk of myocardial ischemia.

This article summary is from the issue dated August 26. 2010. In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. Sirolimus (rapamycin) suppresses mTOR signaling and was studied in this 18-month open-label, randomized, controlled trial involving adults with ADPKD and early chronic kidney disease. Sirolimus at a daily target dose of 2 mg did not halt polycystic kidney growth.

This Images in Clinical Medicine feature is from the issue dated August 26, 2010. A 46-year-old woman presented with a 2-month history of a palpable neck mass. She reported having had no associated symptoms of dysphagia or dyspnea.

This article is from the issue dated August 26, 2010. Thanks to the power of a method to identify etiologic mutations (and hence “causative” genes) in mendelian disease, the molecular mechanisms that give rise to many such diseases are now known. This knowledge has fueled new therapeutic approaches, which are reviewed in this article, the third in the Genomic Medicine series.

This article is from the issue dated August 26, 2010. A 54-year-old man, who had recently been treated for Hodgkin's lymphoma, was admitted to this hospital because of acute unilateral loss of vision. On the morning before admission, the patient noted decreased central vision in his left eye.

This article summary is form the issue dated August 26, 2010. Over the years, physicians have come to rely on certain drugs as standards of care because of their unique clinical effects. Reduction in the supply of these drugs can have dramatic effects on medical practice.

This article summary is from the issue dated August 26, 2010. In 2002, approximately 7.6 million people worldwide died of cancer. These deaths accounted for 13% of all deaths worldwide in that year and, perhaps surprisingly, exceeded the number of deaths from HIV–AIDS, tuberculosis, and malaria combined.

This summary covers the issue dated August 19, 2010. Featured are articles on improved survival with ipilimumab in patients with metastatic melanoma, racial variation in medical outcomes among living kidney donors, early palliative care for patients with metastatic cancer, a randomized trial of tai chi for fibromyalgia, and HPV vaccination mandates; a review article on the emergency treatment of asthma; a case report of a woman with abdominal pain and shock; and Perspective articles on robot-assisted surgery and health care costs, on new priorities for future biomedical innovations, and on Donald Berwick and health care reform.

This article is from the issue dated August 19, 2010. This retrospective study indicates the need for increased attention to health outcomes among demographically diverse living kidney donors.

This article is from the issue dated August 19, 2010. Dr. Donald M. Berwick, pioneer in efforts to improve the quality of medical care and the safety of patients, faces new challenges as he assumes the reins of the Centers for Medicare and Medicaid Services.

This article is from the issue dated August 19, 2010. The authors randomly assigned patients with metastatic lung cancer to receive either standard oncologic care or early palliative care, focused on symptom control and psychosocial support for patients and families, together with standard oncologic care.

A 46-year-old woman who has had two admissions to the intensive care unit for asthma during the past year presents with a 4-day history of upper respiratory illness and a 6-hour history of shortness of breath and wheezing.

This audio summary is for the issue dated August 12, 2010.

This article is from the issue dated August 12, 2010. Molecular dissection in three models of sepsis implicates a signaling pathway in maintaining adhesion of endothelial cells to protect against vascular leak.

This Perspective article is from the issue dated August 12, 2010. After nearly a century of failed attempts, comprehensive healthcare reform was enacted on March 23, 2010, when President Barack Obama signed the Affordable Care Act.

This article is from the issue dated August 12, 2010. Some types of academic–industry relationships are an essential component of the research enterprise in the life sciences. Empirical data show that more than half of academic scientists have such relationships.

This Case Record is from the issue dated August 12, 2010. A 56-year-old woman was admitted because of the sudden onset of dyspnea and hypotension. At 16 years of age, she had received combination chemotherapy and extended-field radiation therapy for Hodgkin's lymphoma. On admission, an electrocardiogram showed an acute myocardial infarction.

This article is from the issue dated August 12, 2010. The author writes that the quarterly “report card” sits on her desk. Only 33% of her patients with diabetes have glycated hemoglobin levels that are at goal. Only 44% have cholesterol levels at goal. 26% have blood pressure at goal.

This article is from the issue dated August 12, 2010. The use of marrow stem cells to treat seven children with severe epidermolysis bullosa caused by loss-of-function mutations in COL7A, the gene encoding type VII collagen (C7), was examined. The investigators observed increases in C7 deposition, the presence of donor cells in the skin, and an amelioration of symptoms.

This summary covers the issue of August 5, 2010. Featured are articles on the treatment of hereditary angioedema; suicide-related events in patients treated with antiepileptic drugs; myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy; and health reform, primary care, and graduate medical education; a review article on transverse myelitis; a Clinical Problem-Solving article on thinking inside the box; and Perspective articles on the “meaningful use” regulation for electronic health records; on how one physician found her way to electronic health records; on bracing for the impact of expanded Second Amendment rights; and on private-party gun sales, regulation, and public safety.

This article is from the issue dated August 5, 2010. A recently developed preparation of C1 inhibitor concentrate was evaluated in patients with hereditary angioedema in two trials.

These article summaries are from the issue dated August 5, 2010. In this large observational study based on data collected as part of clinical care in the United Kingdom, antiepileptic-drug treatment was not associated with an increased risk of suicide-related events among patients with epilepsy, but the use of these drugs was associated with suicide-related events in patients with depression.

And, a physician on the Gulf Coast writes about "Finding My Way to Electronic Health Records."

This Editorial is from the issue dating August 5, 2010.

Also, the Images in Clinical Medicine feature is described.

This article is from the issue dated August 5, 2010. This study shows that myocardial fibrosis is an early characteristic of hypertrophic cardiomyopathy caused by sarcomere mutations.

This article is from the issue dated July 29, 2010. The 2010 healthcare reform bill requires that every eligible American purchase health insurance, but the clinician workforce may not be adequate to provide access for the newly insured.

Also, a Perspective article on 'meaningful use' by David Blumenthal, MD, National Coordinator for Health Information Technology.

This summary covers the issue of July 29, 2010. Featured are articles on sipuleucel-T immunotherapy for castration-resistant prostate cancer, CPR with chest compression alone or with rescue breathing, compression-only CPR or standard CPR in out-of-hospital cardiac arrest, a school-based intervention for diabetes risk reduction, and understanding severe dengue; a review article on acupuncture for chronic low back pain; a case report of a man with perinephric fluid collections and renal failure; and Perspective articles on buying healthcare, the individual mandate, and the US Constitution; on the SGR for physician payment; and on geographic variation in Medicare drug spending.

This article is from the issue dated July 29, 2010. Congress has just extended the life of the sustainable growth rate (SGR) — the formula that Medicare uses to calculate physicians' fees — for 6 more months.

Also, the Images in Clinical Medicine feature is described.

This article is from the issue dated July 29, 2010. In this clinical trial of dispatcher-assisted bystander cardiopulmonary resuscitation (CPR), results were similar with chest compressions alone and with chest compressions plus rescue breathing.

This article is from the issue dated July 29, 2010. In a randomized clinical trial involving patients with out-of-hospital cardiac arrest, 30-day survival rates were similar when compression-only CPR was used and when standard CPR (compression and ventilation) was used.

This Perspective article is from the issue dated July 29, 2010. Three separate cases raising constitutional challenges to the Affordable Care Act are now under way, and together they present issues of great legal complexity. Yet although difficult legal questions must be resolved, a pivotal issue is whose version of events will serve as the judicial analytic filter.

This Perspective article is from the issue dated July 29, 2010. The widespread geographic variation in Medicare spending has garnered a great deal of attention in the health care reform debate. However, analyses to date have not focused on pharmaceutical spending.

This Case Record of the Massachusetts General Hospital is from the issue dated July 29, 2010. A 49-year-old man was admitted to this hospital because of perinephric collections of fluid and acute renal failure. Seven years earlier, routine testing revealed an elevated hematocrit; regular phlebotomy was begun.

This article is from the issue dated July 29, 2010. Severe dengue has been attributed to antibody-dependent enhancement during a second infection with dengue virus. A recent study provides evidence for, and an elaboration of, this mechanism.

This article is from the issue dated July 29, 2010. If the lyrics of the popular Jim Croce song from the early 1970s were adapted for a clinical trialist anthem, the refrain would likely be:

This summary covers the issue of July 15, 2010. Featured are articles on rituximab versus cyclophosphamide for ANCA-associated vasculitis, retinopathy progression in type 2 diabetes, lorcaserin for weight management, early versus standard antiretroviral therapy for HIV-infected adults in Haiti, and metabolic disorders and fat transport; a review article on acute pulmonary embolism; a case report of a request for oocyte retrieval from a woman with anoxic brain injury; and Perspective articles on tobacco control, on the Havasupai Indian tribe case, and on a medical student’s perspective on primary care.

This article is from the issue dated July 15, 2010. This multicenter, randomized, double-blind, double-dummy, noninferiority trial compared rituximab with cyclophosphamide for remission induction in ANCA−associated vasculitis. Rituximab therapy was not inferior to daily cyclophosphamide treatment for remission induction in severe ANCA-associated vasculitis and may be superior in relapsing disease. There is also an accompanying editorial.

Also, the Images in Clinical Medicine feature is described.

This article is from the issue dated July 15, 2010. A standard glucocorticoid regimen plus rituximab was not superior to standard intravenous cyclophosphamide as induction therapy in patients with newly diagnosed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and renal involvement.

This Review article is from the issue dated July 15, 2010. Pulmonary embolism should be suspected in all patients who present with new or worsening dyspnea, chest pain, or sustained hypotension without a clear alternative cause. This review focuses on the optimal diagnostic strategy and management, according to the clinical presentation.

This Case Record of the Massachusetts General Hospital is from the issue dated July 19, 2010. On the ninth day of a 36-year-old woman's coma, the family requested that maximal therapy be resumed, to permit consideration of oocyte retrieval for the purpose of posthumous conception of future offspring. A management decision was made.

This article is from the issue dated July 18, 2010. The transport of lipids into tissues with an elevated rate of cellular metabolism (e.g., skeletal muscle, heart and brown adipose tissue) partly depends on vascular endothelial growth factor B.

This Perspective article is from the issue dated July 15, 2010. Because important strides have been made in tobacco control, it is tempting to believe that the battle is largely won and that we should move on to other pressing public health issues.

This article and related Editorial is from the issue dated July 15, 2010. Patients with type 2 diabetes mellitus were evaluated for progression of diabetic retinopathy after being randomly assigned to receive several medical therapies.

This Perspective article is from the issue dated July 15, 2010. Ishani Ganguli writes that primary care requires a unique skill set — an ability to link complex information, patience, a sophisticated knowledge of the healthcare system, and an appreciation of social context.

This summary covers the issue of July 8, 2010. Featured are articles on adverse events with testosterone administration, late-onset hypogonadism in middle-aged and elderly men, zotarolimus-eluting vs. everolimus-eluting stents, restoring vision after corneal damage, and new recommendations on duty hours from the ACGME task force; review articles on mitral regurgitation due to degenerative mitral-valve disease and on genomewide association studies and assessment of the risk of disease; a case report of a woman with oligomenorrhea and infertility; and Perspective articles on implementing health care reform and Medicare, on the Independent Payment Advisory Board, and on identifying and eliminating the roadblocks to comparative-effectiveness research.

This article is from the issue dated July 8, 2010. The data suggest that late-onset hypogonadism can be defined by the presence of at least three sexual symptoms with a total testosterone level of less than 11 nmol per liter and a free testosterone level of less than 220 pmol per liter.

This article is from the issue dated July 8, 2010. In men 65 years of age or older with low serum testosterone levels and limitations in mobility, improvement in leg-press strength was greater with testosterone therapy than with placebo. However, there were more cardiac adverse events in the testosterone group.

Also, in a second article, a long-term follow-up study of 113 eyes treated with autologous transplantation of limbal stem-cell cultures resulted in a transparent, renewing corneal epithelium restored in 77% of eyes, remaining stable over time.

This summary is from the issue dated July 8, 2010. The Patient Protection and Affordable Care Act creates an Independent Payment Advisory Board (IPAB) to ensure that Medicare spending doesn’t grow too quickly and to make recommendations about controlling national healthcare costs. Timothy Jost explores the IPAB’s structure, mission, and challenges.

This article is from the issue dated July 8, 2010. A 44-year-old man presents with dyspnea and new atrial fibrillation. He received a diagnosis of mild mitral regurgitation at 28 years of age but has not seen a physician in many years. Echocardiography shows a flail posterior leaflet and moderately severe mitral regurgitation. How should this case be managed?

Also, the Images in Clinical Medicine are described.

These articles are from the issue dated July 8, 2010. It describes the design of genomewide association studies and considers the extent to which the data they provide are useful in predicting the risk of disease.

Also, autologous limbal stem cells cultivated on fibrin were used to treat 112 patients with corneal damage, most of whom had burn-dependent limbal stem-cell deficiency.

These articles are from the issue dated July 8, 2010. Dr. Daniel Martin and colleagues describe their experience with a comparative-effectiveness study that highlights important roadblocks and dramatic changes needed in federal infrastructure for such research to be conducted efficiently.

Also, corneal damage may become permanent if the supply of limbal stem cells is compromised. In this long-term follow-up study of 113 eyes treated with autologous transplantation of limbal stem-cell cultures, a transparent, renewing corneal epithelium was restored in 77% of eyes and remained stable over time.

This Case Record of the Massachusetts General Hospital is from the issue dated July 8, 2010. A 32-year-old woman was evaluated because of oligomenorrhea and difficulty becoming pregnant. She became pregnant after two cycles of clomiphene, gestational diabetes developed, and she delivered a healthy infant. Glucose intolerance and amenorrhea persisted after delivery.

Also, in an Original Article, two new-generation drug-eluting coronary stents were compared. Clinical and angiographic outcomes were similar, although there was a somewhat higher rate of stent thrombosis with the zotarolimus stent.

This article is from the issue dated July 8, 2010. More than half the cost of healthcare reform is meant to be paid for through reductions in Medicare spending. Dr. Robert Berenson examines current sources of savings and strategies for identifying future savings in Medicare and its provider-payment system.

This article is from the issue dated July 8, 2010. A task force of the Accreditation Council for Graduate Medical Education (ACGME) has proposed modifications in the current requirements for medical residency training programs, including in the limits on resident hours. This article explains the proposed changes and invites input on the new requirements. 

This article is from the issue dated July 8, 2010. 

This summary covers the issue of July 1, 2010. Featured are articles on stenting vs. endarterectomy for carotid-artery stenosis; HPV and oropharyngeal cancer; an entirely subcutaneous implantable cardioverter–defibrillator; regional variations in diagnostic practices; geographic differences in Medicare spending; and immunosuppression, HIV, and sepsis; a review article on triptan therapy in migraine; a Clinical Problem-Solving article describing a rash hypothesis; and Perspective articles on whether computed tomography is safe, on the uncritical use of high-tech medical imaging, and on hunger and socioeconomic disparities in chronic disease.

This article is from the issue dated July 1, 2010. Human papillomavirus (HPV)–associated oropharyngeal squamous-cell carcinoma differs from oropharyngeal cancers caused by tobacco and other factors. In this study, patients with oropharyngeal cancer were treated with cisplatin plus radiation therapy.

This article is from the issue dated July 2, 2010. In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, myocardial infarction, or death.

Also, the Images in Clinical Medicine feature is described.

This article is from the issue dated July 2, 2010. The authors show substantial variations in diagnostic practices in different regions of the United States. These variations have an important effect on risk adjustment, which, according to the authors, may introduce biases in comparative-effectiveness research, public reporting, and payment reforms.

This article is from the issue dated July 1, 2010. The large variation in Medicare spending across geographic areas has raised concern about inappropriate spending in some areas. In this study, the authors assessed how differences in patients' characteristics contribute to variation in spending.

These articles are from the issue dated July 1, 2010. A 23-year-old woman presents with migraine headaches that are unresponsive to analgesics. Triptan therapy is recommended. Triptans are serotonin agonists that were originally thought to provide migraine relief by causing cranial vasoconstriction; other mechanisms are now also proposed.

Also, an entirely subcutaneous implantable cardioverter–defibrillator without transvenous or epicardial leads was evaluated in two short-term trials to identify a suitable device configuration and assess energy requirements.

These articles are from the issue dated July 1, 2010. Dr. Bruce Hillman and Jeff Goldsmith argue that the root cause of unnecessary use of imaging may be the style and content of clinical education. Minimizing unnecessary imaging will require a change in mindset among physicians.

Also, an entirely subcutaneous implantable cardioverter–defibrillator without transvenous or epicardial leads was evaluated in two short-term trials to identify a suitable device configuration and assess energy requirements.

This Perspective article is from the issue dated July 1, 2010. The rate of food insecurity rose by 32% in 2008, to 14.6% of US households. Drs. Hilary Seligman and Dean Schillinger look at the widening price differential between unhealthful and healthful foods.

This article summary is from the issue dated July 1, 2010. A pathway newly implicated in the immunosuppression observed in persons infected with the human immunodeficiency virus (HIV) may also be pertinent to immunosuppression associated with sepsis.

This article is from the issue dated July 1, 2010. A 40-year-old woman presented with diarrhea, reporting to her physician that she had been having loose stools for 2 years, with 4 to 5 bowel movements per day, progressing over the previous 6 months to 15 large-volume, watery stools daily, including nocturnal stools.

This article is from the issue dated July 1, 2010. Dr. Rebecca Smith-Bindman writes that the risk of cancer from a single CT scan could be as high as 1 in 80 — unacceptably high, given the capacity to reduce these doses of radiation.

This summary covers the issue of June 17, 2010. Featured are articles on nilotinib vs. imatinib for newly diagnosed CML, dasatinib vs. imatinib in newly diagnosed chronic-phase CML, maternal or infant antiretroviral drugs to reduce HIV-1 transmission, antiretroviral regimens in pregnancy and breast-feeding in Botswana, regulation of smoking in public housing, and Wnt signaling and acute myeloid leukemia; a review article on nicotine addiction; a case report of a boy with elevated HIV RNA levels despite antiretroviral medications; and Perspective articles on enrolling pregnant women in research, on health insurance reform and the tensions of federalism, and on Justice John Paul Stevens.

This article is from the issue dated June 17, 2010. In these studies, two new second-generation BCR-ABL kinase inhibitors,nilotinib and dasatinib, are compared with imatinib; these new drugs produce more complete responses and do so faster than imatinib.

Also, the Images in Clinical Medicine feature is described.

This article is from the issue dated June 17, 2010. In these studies, two new second-generation BCR-ABL kinase inhibitors,nilotinib and dasatinib, are compared with imatinib; these new drugs produce more complete responses and do so faster than imatinib. Both also appear to reduce the rate of progression to accelerated-phase and blast-phase disease.

This article is from the issue dated June 10, 2010. Approximately 200,000 infants worldwide become infected with human immunodeficiency virus type 1 (HIV-1) annually through breast-feeding. This randomized trial involved 2369 mother–infant pairs in Malawi.

This article is from the issue dated June 17, 2010. This review gives an account of the cigarette as a highly efficient nicotine delivery system.

This article is from the issue dated June 17, 2010. A 7-year-old boy was seen for treatment of infection with HIV-1. When he was 3 years of age, pulmonary tuberculosis was diagnosed, and at 5 years of age, a diagnosis of HIV-1 infection was made.

Wnt signaling is critical to leukemogenesis in two mouse models of acute myeloid leukemia.

This article is from the issue dated June 17, 2010. The Department of Housing and Urban Development has issued a memorandum encouraging Public Housing Authorities to restrict smoking in public-housing units. The current law relevant to smoking regulations is reviewed and discussed.

This article is from the issue dated June 17, 2010. The global H1N1 influenza pandemic disproportionately affected pregnant women, drawing attention to the fact that although they need safe and effective medical treatment, they have always been a marginalized study population.

This article is from the issue dated June 17, 2010. As healthcare reform is implemented, a new set of federalism-related tensions will arise regarding the best ways to ensure health care coverage for all Americans, secure access to care, promote prevention and wellness, and modernize delivery systems in an effort to achieve better outcomes at lower cost.

This summary covers the issue dated June 10, 2010. Featured are articles on population trends in the incidence and outcomes of acute myocardial infarction, oseltamivir ring prophylaxis for containment of 2009 H1N1 influenza outbreaks, comparative epidemiology of pandemic and seasonal influenza A in households, and valproic acid in pregnancy and congenital malformations; review articles on early Alzheimer’s disease and on recent advances in neuroblastoma; a case report of a woman with flexion of the left hand and foot and difficulty speaking; and Perspective articles on talking about driving and distraction, on health insurance exchanges, and on coronary heart disease and prevention in the United States.

This article is from this issue dated June 10, 2010. In this large community-based study, the incidence of acute myocardial infarction decreased significantly after the year 2000, with an especially marked decrease in ST-segment elevation myocardial infarction. A reduction in the case fatality rate was attributed both to the reduction in ST-segment elevationmyocardial infarctions and a decrease in the rate of death from non–ST-segment elevation myocardial infarction.

The Images in Clinical Medicine feature is also described.

This Perspective article is from the issue dated Jun 10, 2010. A recent report by the Centers for Disease and Control and Prevention documented substantial geographic variation in rates of death due to heart disease. The risk among residents of Oklahoma, the lower Mississippi corridor, and Appalachia, for example, is double that among other Americans; this suggests an association with socioeconomic factors.

This article and Perspective article are from the issue dated June 10, 2010. Pandemic 2009 influenza A (H1N1) virus has caused substantial disease around the world during the past year. In this study from Hong Kong, investigators show that the pandemic and seasonal influenza A viruses behave in a similar manner with respect to the pattern of illness, viral shedding, and secondary attack rates.

This article is from the issue dated June 10, 2010. From June 22 through June 25, 2009, four outbreaks of infection with the pandemic influenza A (H1N1) virus occurred in Singapore military camps. This article reports on the efficacy of ring chemoprophylaxis (geographically targeted containment by means of prophylaxis) with oseltamivir to control outbreaks of 2009 H1N1 influenza in semiclosed environments.

This article is from the issue dated June 10. 2010. It begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.

This article is from the issue dated June 10, 2010. This large case–control study used a European database to assess associations between first-trimester valproic acid monotherapy and 14 malformations reported previously to be linked to valproic acid use in early pregnancy.

This article is from the issue dated June 10, 2010. Although neuroblastoma accounts for disproportionately high morbidity and mortality among childhood cancers, it has one of the highest rates of spontaneous and complete regression. The author discusses recent advances in our understanding of neuroblastoma.

This Case Record of the Massachusetts General Hospital is from the issue dated June 10, 2010. A 29-year-old right-handed woman was seen in the neurology clinic of this hospital because of a 3-year history of involuntary flexion of the left hand and increasing difficulty moving the left foot. Examination revealed dystonic movements and posturing of the left arm, hand, and foot. Brain imaging was normal. During the next 2.5 years, symptoms gradually worsened, and difficulty swallowing and speaking developed. A diagnostic test was performed.

This Perspective article is from the issue dated June 10, 2010. The author argues that it's not uncommon got about habits associated with harm, including helmets, seat belts, condoms, cigarettes, alcohol, and drugs. And as technology evolves, our questions must be updated in keeping with the risks: it's time for us to ask patients about driving and distraction.

This Perspective article is from the issue dated June 10, 2010. Exchanges have been an important element of almost every recent proposal for national healthcare reform. The author asks: how does the Patient Protection and Affordable Care Act  envision the function and mission of exchanges, and how do exchanges affect the organization of care?

This summary covers the issue of June 3, 2010. Featured are articles on longer therapy, amenorrhea, and survival in early breast cancer; retropubic versus transobturator midurethral slings for stress incontinence; deep-brain stimulation for Parkinson’s disease; genetic susceptibility to infectious disease; standard of care in emergencies; and the mitochondrion in inflammation; a review article on dietary therapy in hypertension; a Clinical Problem-Solving article describing a woman with aphasia; and Perspective articles on the curious case of colchicine, on the growing importance of the community health center, and on the cost implications of health care reform.

This article is from the issue dated June 3, 2010. In node-positive breast cancer, adjuvant doxorubicin plus cyclophosphamide followed by docetaxel was associated with significantly better disease-free survival than the three drugs together or doxorubicin–docetaxel. Premenopausal women who became amenorrheic as a consequence of treatment had significantly improved overall and disease-free survival.

A related Editorial follows.

This article is from the issue dated June 3, 2010. In this randomized trial, two surgical approaches for the treatment of stress urinary incontinence had similar cure rates, although the complications differed by group.

This article is from the issue dated June 3, 2010. In this trial of deep-brain stimulation targeted to either the globus pallidus interna or the subthalamic nucleus in patients with advanced Parkinson’s disease, the patients assigned to pallidal stimulation and those assigned to subthalamic stimulation had a similar improvement in motor function.

This article is from the issue dated June 3, 2010. A 57-year-old patient has a blood pressure reading of 155/95 mm Hg. Dietary therapy is recommended. Dietary changes that have been shown to reduce blood pressure include reduced sodium intake, reduced caloric intake, and diets high in fruits, vegetables, low-fat dairy products, whole grains, poultry, fish, nuts, and unsaturated vegetable oils.

This Clinical Problem Solving article is from the issue dated June 3, 2010. A 34-year-old woman presented with aphasia. Two hours earlier, her arms and legs had suddenly begun shaking. The episode lasted several seconds. Immediately afterward, she was unable to speak or to move her limbs on the right side.

This Health, Law, Ethics, and Human Rights article is from the issue dated June 3, 2010. After 9/11, policy analysts speculated that clinicians may be reluctant to provide care during disasters because of fear of medical liability and proposed policies to create different standards of care for emergencies. In the context of the Haitian earthquake, George Annas argues that redefining the standard of care in disasters is neither necessary nor justified.

This article is from the issue dated June 3, 2010. Sterile inflammation, which occurs in the post-traumatic systemic inflammatory response and other conditions such as myocardial infarction, may be spurred by mitochondria released from dying cells.

This Perspective article is from the issue dated June 3, 2010. Drs. Aaron Kesselheim and Daniel Solomon write that it came as a surprise to many patients and physicians that the FDA not only approved the new version of colchicine but also granted the manufacturer 3 years of market exclusivity for this ancient drug

This article is from the issue dated June 3, 2010. This study shows that variants of the CISH gene are associated with susceptibility to bacteremia, malaria,and tuberculosis.

This article is from the issue dated June 3, 2010. The Patient Protection and Affordable Care Act enables community health centers to serve nearly 20 million new patients while adding an estimated 15,000 providers to their staffs by 2015. Dr. Eli Adashi and colleagues describe the “new” community health centers.

This Perspective article is from the issue dated June 3, 2010. Jonathan Gruber argues that by the second decade, the Patient Protection and Affordable Care Act will have reduced national health care spending.

This summary covers the issue of May 27, 2010. Featured are articles on target ranges of oxygen saturation in extremely preterm infants, early CPAP versus surfactant in extremely preterm infants, and a comparison of shunt types in the Norwood procedure for single-ventricle lesions; review articles on infectious mononucleosis and on genomic medicine — an updated primer; a case report of a man with cough and pain in the left shoulder; and Perspective articles on pandemic vaccines — the legal landscape, on Medicaid and health care reform, and on fixing Medicare’s physician payment system.

This large randomized trial with a 2-by-2 factorial design compared with a lower target range of oxygen saturation (85 to 89%) with a higher target range (91 to 95%) in extremely preterm infants.

Also, the Images in Clinical Medicine are described.

This article is from the issue dated May 27, 2010. In this part of a randomized, 2-by-2 factorial trial involving extremely preterm infants, use of intubation and surfactant treatment (within 1 hour after birth) was compared with initiation of continuous positive airway pressure (CPAP) in the delivery room and subsequent use of a protocol-driven limited ventilation strategy.

This article is from the issue dated May 27, 2010. Hypoplastic left heart syndrome is a complex congenital heart lesion that requires a three-stage procedure for surgical palliation. This clinical trial examines two approaches to the first stage of the procedure, and the results provide important guidance for the most appropriate surgical management of this serious lesion.

This Review Article is from the issue dated May 27, 2010. This review article describes the fundamental bases of genetic and genomic discovery and launches a new series: Genomic Medicine.

This Perspective article is from the issue dated May 27, 2010. Vaccines and vaccination law feature prominently in pandemic preparedness plans. The recent H1N1 influenza vaccine program provides an important opportunity to assess the complex and perhaps paradoxical effects of vaccine laws during a pandemic.

This article is from the issue dated May 27, 2010. The recently passed US healthcare reform law envisions a health care system that rests atop a four-legged stool consisting of employer-sponsored health plans, coverage purchased through state-based exchanges, Medicare, and Medicaid. Each leg faces important challenges, none more than Medicaid.

This article is from the week of May 27, 2010. Congress must confront another healthcare issue that is perhaps even more politically difficult than healthcare reform: reform of Medicare's physician payment system. On April 15, Congress voted to postpone a 21% reduction in Medicare fees that was to have gone into effect April 1, but a longer-term solution is not yet in sight.

This Case Study of the Massachusetts General Hospital is from the issue dated May 27, 2010. A 48-year-old man was seen in the orthopedic clinic of this hospital because of cough, pain in the left shoulder, and a radiographically lucent lesion in the scapula.

This summary covers the issue of May 20, 2010. Featured are articles on endovascular versus open repair of abdominal aortic aneurysm, endovascular repair of aortic aneurysm in patients physically ineligible for open repair, long-term outcome of repair of abdominal aortic aneurysm, gene-expression profiling after cardiac transplantation, L-histidine decarboxylase and Tourette’s syndrome, and sperm and the proton channel; a review article on susceptibility pathways in Fanconi’s anemia and breast cancer; a case report of a woman with mammographically detected early breast cancer; and Perspective articles on pediatric mental health care, on gene patenting, and on Haiti earthquake relief, phase two.

This article is from the issue dated May 20, 2010. Patients with large abdominal aortic aneurysms were assigned to undergo either endovascular repair or open surgical repair. Operative mortality was lower with endovascular repair, but at a median of 6 years, there was no significant difference between groups in total mortality or aneurysm-related mortality.

This article is from the issue dated May 20, 2010. Patients with large abdominal aortic aneurysms who were physically ineligible for open surgical repair were assigned to undergo endovascular repair or to receive no intervention. At a median of 3 years, aneurysm-related mortality was significantly lower with endovascular repair, but there was no difference in total mortality.

Also, the Images in Clinical Medicine are described.

This article is from the issue dated May 13, 2010. Patients with large abdominal aortic aneurysms were assigned to undergo open surgical repair or endovascular repair. At 6 years, the cumulative survival rates did not differ significantly between groups.

This article is from the issue dated May 20, 2010. Patients were assigned to monitoring for rejection after cardiac transplantation either according to the standard practice of endomyocardial biopsies or with gene-expression profiling. At 19 months, the rates of rejection were similar in the two groups.

This article is from the issue dated May 20. 2010. Fanconi’s anemia is a rare disorder that arises from defective repair of damaged DNA. Of the 13 Fanconi’s anemia genes, 3 are breast-cancer–susceptibility genes. One is identical to BRCA2. Studies of a rare disorder can illuminate a common disorder.

This Case Record of the Massachusetts General Hospital is from the issue dated May 20, 2010. An 85-year-old woman had poorly differentiated invasive ductal cancer (positive for estrogen and progesterone receptors and HER2) with no clinical evidence of lymph-node or distant metastases.

Also, the transition from quiescence of the sperm in the epididymis to capacitation in the female reproductive tract depends on alkalinization of the intracellular milieu. A recent study underscores the role of a particular proton channel in the process of alkalinization.

This article is from the issue dated May 20, 2010. Are human genes and the process of comparing DNA sequences patentable? Dr. Aaron Kesselheim and Michelle Mello describe a recent federal district court decision that reignites a long-simmering debate about the patentability of genes.

This article summary is from the issue dated May 20, 2010. One of the most talked-about features of the draft revisions for the DSM-V is a new diagnostic category for children: temper dysregulation disorder with dysphoria (TDD). Erik Parens and colleagues argue that this new diagnosis may not help troubled children unless we get serious about reforming pediatric mental health care.

This Perspective article is from the issue dated May 20, 2010. Dr. Dominique Bayard worked in a makeshift hospital in Tabarre, a northeast section of Port-au-Prince, where the hospital staff treated more than 800 patients a day for infections, disabilities, complications from delayed treatment, respiratory illness, sexually-transmitted disease, and chronic disease

This summary covers the issue of May 13, 2010. Featured are articles on bisphosphonates and fractures of the subtrochanteric or diaphyseal femur, robot-assisted therapy for upper-limb impairment after stroke, maternal vitamin A supplementation and lung function in offspring, quality indicators for colonoscopy and the risk of interval cancer, and whistle-blowers’ experiences in fraud litigation against pharmaceutical companies; a review article on hospital-acquired infections due to gram-negative bacteria; a case report of a woman with dizziness and falls; and Perspective articles on tobacco product regulation and on treatment decisions after brain injury.

Recent case reports and series have identified a subgroup of atypical femoral-shaft fractures associated with bisphosphonate use. This study analyzed data from three large, randomized bisphosphonate trials. Subtrochanteric or diaphyseal femur fractures were very rare, even among women who had been treated with bisphosphonates for as long as 10 years. In patients with osteoporosis, proven benefits for fracture reduction appear to outweigh the possible risk of femoral-shaft fractures.

There is an accompanying Editorial.

This Review Article is from the issue dated May 13, 2010. Hospital-acquired infections are most commonly associated with mechanical ventilation, invasive medical devices, or surgical procedures. Gram-negative bacteria are responsible for more than 30% of hospital-acquired infections and predominate in hospital-acquired pneumonia. They are highly efficient at up-regulating or acquiring mechanisms of antibiotic drug resistance, especially in the presence of antibiotic selection pressure. This review updates what clinicians should know about these often life-threatening infections.

This article is from the issue dated May 13, 2010. In this randomized study evaluating rehabilitative therapies in patients with long-term upper-limb impairment after stroke, outcomes at 12 weeks were similar with robot-assisted therapy, intensive comparison therapy, and usual care. In secondary analyses, modest improvements were observed over 36 weeks in both intensive-therapy groups, as compared with the usual-care group.

This article is from the issue dated May 13, 2010. In this article, the investigators examined a subgroup of children whose mothers had participated in a trial of prenatal vitamin A supplementation that was performed in an area of Nepal where traditionally there is suboptimal nutrition. The lung function of children whose mothers had received vitamin A supplementation during pregnancy was 2 to 3% better than that of children whose mothers had received placebo.

This Perspective article is from the issue dated May 13, 2010. On June 22, 2009, President Barack Obama signed the Family Smoking Prevention and Tobacco Control Act. This historic legislation provides the Food and Drug Administration (FDA) with the authority to regulate tobacco products, the leading cause of preventable death in the United States.

This Perspective article is from the issue dated May 13, 2010. Many patients with sudden severe brain injury from stroke, trauma, or cardiac arrest die after family members and clinicians decide, given a poor prognosis, to withdraw treatment. Although it's difficult to estimate precisely how prevalent this trajectory to death is, as many as 60% of deaths from stroke, heart disease, and traumatic brain injury may involve some kind of treatment withdrawal, which makes it one of the most common pathways to death in the United States.

This article is from the issue dated May 13, 2010. The authors interviewed 26 whistle-blowers who had initiated qui tam cases against pharmaceutical companies that were successfully prosecuted for health care fraud. The whistle-blowers reported undergoing substantial personal hardships during their legal cases.

This Case Record of the Massachusetts General Hospital is from the issue dated May 13, 2010. A 54-year-old woman was admitted to this hospital because of 2 months of episodes of dizziness resulting in falls, which occurred only when standing and were associated with diaphoresis, weakness in the legs, and palpitations.

This summary covers the issue of May 6, 2010. Featured are articles on everolimus-eluting versus paclitaxel-eluting stents, pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis, generalized vitiligo and tyrosinase, effect of bar-code technology on the safety of medication administration, information technology and global surveillance of H1N1, and susceptibility to coronary artery disease; a review article on clinical aspects of pandemic 2009 influenza A (H1N1) virus infection; a Clinical Problem-Solving article describing a man who had a syncopal event while watching a baseball game; and Perspective articles on a 2020 vision for healthy people, on why we don’t spend enough on public health, and on syphilis and social upheaval in China.

This article and editorial is from the issue dated May 6, 2010. This trial compared the effectiveness of an everolimus-eluting coronary stent with that of a paclitaxel-eluting stent in patients with coronary artery disease. Clinical outcomes at one year were superior with the everolimus-eluting stent in patients without diabetes, but not in patients with diabetes.

This article is from the issue dated May 6, 2010. Real-time forms of technology online are creating new ways to detect and track emerging disease threats, even weak signals from diverse areas. View an interactive map, based on data from more than 87,000 reports, that helped track the 2009 H1N1 pandemic at NEJM's website.

This article is from the issue dated May 6, 2010. Genomewide association studies have implicated a region on chromosome 9p21 in coronary artery disease. This association is probably driven by two genes that mediate the proliferation of aortic smooth-muscle cells.

This Perspective article is from the issue dated May 6, 2010. Dr. Howard Koh writes that the Healthy People initiative aims to unify national dialogue about health, motivate action, and encourage new directions in health promotion, providing a public health roadmap and compass for the country.

This Perspective article is from the issue dated May 6, 2010. It is generally acknowledged that public health is systematically underfunded. David Hemenway describes four key reasons why.

This article is from the issue dated May 6, 2010. In adults who had nonalcoholic steatohepatitis, vitamin E therapy was associated with a significantly higher rate of improvement than was placebo. Significant benefits of pioglitazone over placebo were shown for some secondary outcomes.

Also, the Images in Clinical Medicine are presented.

These articles are from the issue dated May 6, 2010. In a Clinical Problem-Solving article, a case is described of a 45-year-old man who presented to the emergency room after a syncopal episode that occurred while he was watching a baseball game. He noted nausea and diaphoresis but reported no chest pain before or after the event.

Also, an Original Article describes the results of a genomewide association study of generalized vitiligo implicate genes involved in the immune response and also a variant of TYR, which encodes tyrosinase.

This article is from the issue dated May 6, 2010. This review by WHO experts summarizes the virologic, epidemiologic, and clinical data on the 2009 H1N1 virus and assesses future directions.

These articles are from the issue dated May 6, 2010. A Perspective article looks at syphilis, which was nearly eliminated from China 50 years ago but is now the most commonly reported communicable disease in Shanghai. Dr. Joseph Tucker and colleagues write that the Chinese syphilis epidemic holds important lessons about social and environmental influences on sexual health.

Also, a Special Article looks at the effects on medication administration safety after implementation of a bar-code system.

This summary covers the issue of April 29, 2010. Featured are articles on the effects of combination lipid therapy in type 2 diabetes mellitus, effects of intensive blood-pressure control in type 2 diabetes mellitus, aspirin plus heparin or aspirin alone in women with recurrent miscarriage, and a snapshot from one primary care practice; review articles on Helicobacter pylori infection and on pancreatic cancer; a case report of a girl with watery diarrhea and poor weight gain; and Perspective articles on medication adherence as a priority for health care reform, on specialist physician practices as patient-centered medical homes, on engaging specialists in performance-incentive programs, and on the value of DNKs.

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This summary is for the week of April 29, 2010. In a randomized trial, 5518 patients with type 2 diabetes mellitus who were at high risk for cardiovascular events were all treated with simvastatin and assigned to receive either fenofibrate or placebo. At a mean follow-up of 4.7 years, the rates of the primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) did not differ significantly between the two study groups.

This article and related Editorial is from the issue dated April 29, 2010. In a randomized trial, 4733 patients with type 2 diabetes mellituswho were at high risk for cardiovascular events received treatment aimed at a target systolic blood pressure of less than 120 mm Hg or less than 140 mm Hg. At a mean follow-up of 4.7 years, the rates of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were not significantly different between the two trial groups.

This article and related Editorial is from the issue dated April 29, 2010. Aspirin and low-molecular-weight heparin are often prescribed to women with unexplained recurrent miscarriage, but their benefit is unclear.

This Clinical Practice article is from the issue dated April 29, 2010. A 29-year-old man presents with intermittent epigastric discomfort, without weight loss or evidence of gastrointestinal bleeding. He reports no use of aspirin or nonsteroidal anti-inflammatory drugs. A serologic test for Helicobacter pylori is positive, and he receives a 10-day course of omeprazole, amoxicillin, and clarithromycin. Six weeks later, he returns with the same symptoms.

This article is from the issue dated April 29, 2010. Deaths from pancreatic ductal adenocarcinoma, also known as pancreatic cancer, rank fourth among cancer-related deaths in the United States, yet the causes of pancreatic cancer remain unknown. This review article summarizes recent progress in the understanding and management of pancreatic cancer.

This Perspective article is from the issue dated April 29, 2010. Poor adherence to treatment regimens has long been recognized as a substantial roadblock to achieving better outcomes for patients. Data show that as many as half of all patients do not adhere faithfully to their prescription-medication regimens — and the result is more than $100 billion spent each year on avoidable hospitalizations.

Both articles are from the issue dated April 29, 2010. In an Occasional Note, a physician describes the daily work in his primary care practice and documents the high volume of tasks involved in patient care aside from face-to-face visits.

And a Perspective article looks at the concerns of specialist physicians regarding the medical home's implications for their practices.

This Perspective article is from the issue dated April 29, 2010- What is the value of the "Did Not Keep" Patients? Also, Images in Clinical Medicine are presented.

This Perspective article is from the issue dated April 29, 2010. To have a meaningful impact on the quality of care, pay-for-performance programs and newer-generation quality-incentive programs must engage more specialists.

This summary covers the issue of April 22, 2010. Featured are articles on nateglinide and progression of impaired glucose tolerance, effect of valsartan on the incidence of diabetes and cardiovascular events, a step-up approach or open necrosectomy in necrotizing pancreatitis, and RFX6 and the pancreatic beta cell; review articles on epidural analgesia for labor and delivery and on the recent evolution of vaccines against Neisseria meningitidis infection; a case report of a man with progressive dyspnea; and Perspective articles on medical marijuana and the law, on childhood obesity prevention from pregnancy and infancy onward, and on increasing the value of the state medical license.

This article is from the issue dated April 22, 2010. Among patients with impaired glucose tolerance, the short-acting insulin secretagogue nateglinide did not reduce the incidence of diabetes over the course of 5 years. Nateglinide also did not reduce the risk of cardiovascular events.

This article is from the issue dated April 22, 2010. In this large clinical trial, the angiotensin-receptor blocker valsartan reduced the risk of diabetes in patients with impaired glucose tolerance. However, the effect was small, and there was no reduction in the rate of cardiovascular events. There is also a related Editorial.

This article is from the issue dated April 22, 2010. In patients with necrotizing pancreatitis, a less invasive step-up approach (percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy) was associated with fewer complications than open necrosectomy.

This article is from the issue dated April 22, 2010. A 30-year-old pregnant woman is undergoing induction of labor and is experiencing severe pain despite intravenous opioid administration. Epidural analgesia is recommended.

This article is from the issue dated April 22, 2010. This review provides an update on our understanding of immunity against meningococcal infection. Knowledge of the meningococcal genome has led to identification of novel antigens.

This Case Record of the Massachusetts General Hospital is from the issue dated April 22, 2010. An 89-year-old man had experienced progressive dyspnea for 6 months, worsening over the past 3 days. He had a history of exposure to asbestos and had smoked cigarettes for many years.

This article is from the issue dated April 22, 2010. The RFX6 transcription factor is critical to the development and function of beta cells — a finding that may inform experimental approaches to the treatment of diabetes mellitus in patients with beta-cell deficiency.

This Perspective article is from the issue dated April 22, 2010. The US legal landscape surrounding “medical marijuana” is complex and rapidly changing. Diane Hoffmann and Ellen Weber describe evolving legislation.

This Perspective article is from the issue dated April 22, 2010. The Let’s Move campaign has potential for altering the course of the childhood obesity crisis. Janet Wojcicki and Dr. Melvin Heyman argue that to be a truly successful program, the campaign must stimulate prevention efforts targeting the youngest Americans — those under 2 years of age and preschoolers.

This Perspective article is from the issue dated April 22, 2010. Dr. John Herman writes that state licensing boards can and should assume a more proactive role in assuring the public that a medical license represents a valid certificate of a physician’s competence.

This article is from the issue dated April 26, 2010. It describes the Images in Clinical Medicine feature.

This summary covers the issue dated April 15, 2010. Featured are articles on lenient vs. strict rate control for atrial fibrillation, dual antiplatelet therapy and drug-eluting stents, therapy for Crohn’s disease, and alglucosidase alfa in late-onset Pompe’s disease; review articles on outpatient management of severe COPD and on aggressive lymphomas; a case report of a woman with lethargy, confusion, and abnormalities on brain imaging; and Perspective articles on malpractice reform, on the potential health effects of Citizens United, and on feeling disconnected from patients lost to follow-up.

This article is from the issue dated April 15, 2010. In patients with atrial fibrillation, lenient rate control (resting heart rate, <110 beats per minute) was not inferior to strict rate control (resting heart rate, <80 beats per minute). There is also a related Editorial.

This article is from the issue dated April 15, 2010. In two trials, 2701 patients were randomly assigned to receive drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of myocardial infarction or death from cardiac causes. Data from the two trials were merged for analysis.

This article is from the issue dated April 19, 2010. In this randomized trial comparing infliximab, azathioprine, and combination therapy in adults with moderate-to-severe Crohn's disease, infliximab and combination therapy were superior to azathioprine. Adverse events were similar in the three groups.

Pompe's disease is caused by a deficiency of acid alpha glucosidase, which degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. In this randomized, placebo-controlled trial of a recombinant human acid alpha glucosidase, walking distance improved and pulmonary function stabilizedover an 18-month period in patients treated with the active drug.

This Review Article is from the issue dated April 15, 2010. This review summarizes recent evidence concerning molecular changes in the commonest type of lymphoma, diffuse large-B-cell lymphoma. Detailed studies have revealed three subtypes, each with distinctive clinical and molecular features. The molecular dissection of these tumors is uncovering new possibilities for treatment, some of which are already in clinical trials.

This article is from the issue dated April 15, 2010. A 67-year-old man presents with progressive dyspnea. He has smoked cigarettes since he was 15 years of age. Worsening breathlessness forced him to retire as a laborer. His physical examination is notable for distant breath sounds on auscultation, with a prolonged expiratory phase.

Also, the Images in Clinical Medicine feature is described.

This Perspective article is from the issue dated April 15, 2010. In February 2010, the Illinois Supreme Court ruled that the state's cap on noneconomic damages in medical malpractice cases violated the Illinois constitution. This development has contributed to growing pessimism about traditional approaches to medical liability reform. In some quarters, interest is shifting to innovative reforms that can be implemented by health care institutions and liability insurers without requiring changes in the law.

This Case Record of the Massachusetts General Hospital is from the issue dated April 15, 2010. A 69-year-old woman presented to this hospital because of a 2-month period of increasing apathy, confusion, and depression. She had a history of connective-tissue disease and idiopathic thrombocytopenic purpura. Ten days before admission, a magnetic resonance image of the brain was obtained, which was abnormal.

This Perspective article is from the issue dated April 15, 2010. On January 21, 2010, the U.S. Supreme Court reached one of its most controversial decisions in years, with Citizens United v. Federal Election Commission. Although it may not initially appear to concern health, Citizens United has important implications for health care providers and public health.

This Perspective article is from the issue dated April 15, 2010. "It was one of those oh-no moments: I had lost a patient and I wanted to rewind the clock and start over. I don't mean lost to the Grim Reaper — just to the great wide world."

Lung function was measured in firefighters and emergency-medical-service workers who responded to the collapse of the World Trade Center towers in New York on September 11, 2001. There was initial marked loss in lung-function measures without substantial recovery during the following seven years.

Also, the Images in Clinical Medicine feature is described.

This Perspective article is from the issue dated April 8, 2010. Henry Aaron and Robert Reischauer write that passage of healthcare reform is a cause for celebration, but supporters must prepare to meet the serious challenges that remain.

Also, this week's Images in Clinical Medicine feature is described.

This article is from the issue dated April 8, 2010. In this trial comparing cisplatin plus gemcitabine with gemcitabine alone for the treatment of biliary tract cancer, overall survival and progression-free survival were improved with the use of cisplatin plus gemcitabine.

This article is from the issue dated April 8, 2010. Supplementation with 1000 mg of vitamin C and 400 IU of vitamin E, beginning in the 9th to 16th week of pregnancy, did not reduce the rates of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension.

This article is from the issue dated April 8, 2010. Patients re-treated with peginterferon alfa-2a and ribavirin combined with telaprevir were more likely to have a sustained response than patients retreated with peginterferon alfa-2a and ribavirin alone.

This article is from the issue dated April 8, 2010. In this demonstration experiment on the structure of an internal-medicine teaching service, the investigators found that a model with two attending physicians and limited patient-staff census resulted in greater satisfaction on the part of trainees and attending physicians than the standard approach.

This article is from the issue dated April 8, 2010. This article reviews the rationale for treatment with oral phosphate binders, discusses evidence supporting the use of available agents, and suggests an approach for clinical practice.

This Case Study of the Massachusetts General Hospital is from the issue dated April 8, 2010. A 37-year-old woman had vertigo, weakness and numbness of the left side, and shaking of the left leg. MRI revealed a mass in the right parietal lobe of the brain.

This Clinical Implications of Basic Research article is from the issue dated April 8, 2010. Drug interactions may be explained by the extent to which a combination of drugs balances or offsets the balance of the metabolism of different cellular components.

This Perspective article is from the issue dated April 8, 2010. One might imagine that medical educators have attempted to incorporate cost consciousness into their teaching, but such efforts have been remarkably few. Dr. Molly Cooke discusses how medical education can address the urgent issue of cost.

This summary covers the issue of April 1, 2010. Featured are articles on trajectories of disability in the last year of life, whole-genome sequencing and causes of disease, effect of dutasteride on the risk of prostate cancer, glycogenin-1 deficiency and inactivated priming of glycogen synthesis, and advance directives and decision making before death; a review article on prolactinomas; a Clinical Problem-Solving article describing more than meets the ear; and Perspective articles on modernizing device regulation, on improving the security and privacy of implantable medical devices, on health care and federal debt in the United States, and on the FDA and safe use of long-acting beta-agonists in the treatment of asthma.

This Perspective article is from the issue dated April 1, 2010. The most important force shaping the US healthcare system over the coming decades may well be the federal debt. The government now pays for approximately half of all health care costs in the United States, and projections of growing federal debt largely reflect anticipated increases in health care spending.

This Perspective article is from the issue dated April 1, 2010. For over a decade, the Food and Drug Administration (FDA) and the medical community have discussed how to safely use long-acting beta-agonists. The Serevent nationwide surveillance study suggested an increased risk of asthma-related death in patients treated with salmeterol as compared with albuterol, a short-acting beta-agonist.

Also: this week's Images in Clinical Medicine.

This Perspective article is from issue dated April 1, 2010. Like the drug supply of a generation ago, today, medical devices face a security vulnerability that must be addressed through regulatory and scientific actions.

This article is from the issue dated April 1, 2010. Data from a national study showed that more than one quarter of older adults who died between 2000 and 2006 required decision making at the end of life but lacked decision-making capacity.

This Perspective article is from the issue dated April 1, 2010. The Food and Drug Administration (FDA) is known for its rigor in regulating drugs, not devices. That may be about to change. In recent years, well-publicized device recalls and lawsuits have led to complaints that the FDA does not do enough to keep unsafe devices off the market.

This Clinical Problem-Solving article is from the issue dated April 1, 2010. A 62-year-old, generally healthy man presented with a "clogged" sensation and a 6-week history of diminished hearing in his right ear. He had no tinnitus, ear pain, or dizziness.

This article is from the issue dated April 1, 2010. This longitudinal study involving older adults identified five trajectories during the last year of life: no disability, catastrophic disability, accelerated disability, progressive disability, and persistently severe disability.

Also, a study of Charcot–Marie–Tooth disease involving the sequencing of an affected person's whole genome.

This Clinical Practice article is from the issue dated April 1, 2010. A 42-year-old man presents with decreased libido, erectile dysfunction, and headaches. He reports no weight change, gynecomastia, fatigue, or other symptoms.

This article, from the issue dated April 1, 2010, describes a patient with muscle weakness and cardiac arrhythmia, marked depletion of glycogen was shown in skeletal muscle and an accumulation of abnormal storage material was shown in the heart.

Plus, an Editorial related to Liviing Wills.

This Editorial is related to the Original Article regarding the genetic diagnosis of diseases that are genetically heterogeneous — such as Charcot–Marie–Tooth disease — can be a challenge, and a study that involved the sequencing of an affected person's whole genome.

Also, dutasteride, an inhibitor of 5-reductase in the prostate, was tested in a large, randomized trial to determine its abilityto prevent prostate cancer.

This summary covers the issue of March 25, 2010. Featured are articles on rifaximin treatment in hepatic encephalopathy, apolipoprotein C3 gene variants in nonalcoholic fatty liver disease, prevalence of diabetes among men and women in China, a loss-of-function mutation in NaPi-IIa and renal Fanconi’s syndrome, hospital volume and 30-day mortality for three common medical conditions, and isocitrate dehydrogenase and glioma; a review article on stereotactic radiosurgery for the management of brain metastases; a case report of a woman with paresthesias and ataxia; and Perspective articles on global climate change and infectious diseases, on patients, doctors, and the Internet, and on whether electronic clinical documentation can help prevent diagnostic errors.

This article is from the issue dated March 25, 2010. It covers a placebo-controlled, randomized trial of patients with a history of recurrent hepatic encephalopathy resulting from chronic liver disease, rifaximin (at a dose of 550 mg twice daily) prevented episodes of hepatic encephalopathy and hospitalizations involving hepatic encephalopathy.

This article is from the issue dated March 25, 2010. In 95 Asian Indian men, single-nucleotide polymorphisms in the apolipoprotein C3 gene were genotyped to detect variant alleles associated with hypertriglyceridemia.

This article, from the issue dated March 25, 2010, presents the results of the China National Diabetes and Metabolic Disorders study, which was performed in 2007–2008 to estimate the prevalence of diabetes among Chinese adults.

Also, this week's Images in Clinical Medicine are described.

This Clinical Therapeutics article is from the issue dated March 25, 2010. A 50-year-old man with a history of lung cancer presents with headaches and right-arm numbness; he is found to have a single brain metastasis. Stereotactic radiosurgery is recommended as part of his care.

This Special Article is from the issue dated March 25, 2010. In this analysis of claims data from Medicare beneficiaries who were hospitalized for acute myocardial infarction, heart failure, or pneumonia, admission to higher-volume hospitals was associated with lower mortality.

Also, in an Original Article from the same issue, two siblings from a consanguineous family who had autosomal recessive renal Fanconi's syndrome and hypophosphatemic rickets were found to have a homozygous in-frame duplication of 21 bp in SLC34A1, the gene that encodes the renal sodium–phosphate cotransporter NaPi-IIa.

This Case Record of the Massachusetts General Hospital is from the issue dated March 25, 2010. A 37-year-old right-handed woman was admitted to the hospital because of a seven-month history of intermittent paresthesias, followed by slurred speech, headaches, ataxia, and cognitive difficulties. Treatment with corticosteroids, verapamil, and azathioprine resulted in little improvement.

This Perspective article is from the issue dated March 25, 2010. Climate change will have enormous implications for human health, especially for the burden of vectorborne and waterborne infectious diseases.

This Clinical Implications of Basic Research article is from the issue dated March 25, 2010. A mutation in IDH1, which encodes an isocitrate dehydrogenase, is associated with susceptibility to glioma. This mutation results in an acquired enzyme activity that points to a potential biomarker >of the mutant tumor.

This Perspectives article is from the issue dated March 25, 2010. Nothing has changed clinical practice more fundamentally than one recent innovation: the Internet. Its profound effects derive from the fact that while previous technologies have been fully under doctors' control, the Internet is equally in the hands of patients.

This Perspective article is from the issue dated March 25, 2010. The United States is about to invest nearly $50 billion in health information technology (HIT) in an attempt to push the country to a tipping point with respect to the adoption of computerized records. A fundamental question is how best to design electronic health records to enhance clinicians' workflow and the quality of care.

This summary covers the issue of March 18, 2010. Featured are articles on step-up therapy for children with uncontrolled asthma, performance of common genetic variants in breast-cancer risk models, nationwide public-access defibrillation in Japan, corticosteroid suppression of VEGF-A in infantile hemangioma-derived stem cells, and physician cost profiling; a review article on vertebral osteomyelitis; a case report of a woman with hypercalcemia and a pelvic mass; and Perspective articles on how to think about future health care spending, on AIDS in America, and on five next steps for a new national program for comparative-effectiveness research.

Many children have uncontrolled asthma symptoms when treated with low-dose inhaled corticosteroids (ICS). In this three-way crossover trial, the investigators asked whether doubling the dose of ICS, adding a leukotriene-receptor antagonist to the ICS, or adding a long-acting beta-agonist to the ICS would result in better asthma control.

An Editorial follows this article.

The principal tool used to estimate a woman's risk of breast cancer is the Breast Cancer Risk Assessment Tool, or the Gail model, which includes the number of first-degree relatives with breast cancer, age at menarche, age at first live birth, and number of previous breast biopsies. In this study, the addition of data on genetic variants associated with breast cancer yielded only a minor improvement in the performance of the model.

A related Editorial follows.

These Images in Clinical Medicine are from the issue dated March 18, 2010.

This article is from the issue dated March 18, 2010. Increasingly widespread public access to automatic external defibrillators in Japan was associated with earlier administration of shocks by laypersons and an increase in the frequency of survival with minimal neurologic impairment after an out-of-hospital cardiac arrest.

This article is from the issue dated March 18, 2010. Some insurance companies are offering patients incentives to choose lower-cost physicians. This study shows that the current methods used to generate physicians' cost profiles do not have high reliability and that the systems using these cost profiles to identify lower-cost physicians will incorrectly classify many physicians.

This Clinical Practice article is from the issue dated March 18, 2010. A 57-year-old man presents 2 weeks after prostate biopsy with fever, chills, and new lumbar back pain. His temperature is 39.7°C; he has an enlarged, tender prostate and lumbar spine tenderness. His white-cell count is 9100 per cubic millimeter, and the C-reactive protein level is 343 mg per liter. Urine and blood cultures reveal multidrug-resistant extended-spectrum β-lactamase–producing Escherichia coli susceptible to imipenem. How should he be evaluated and treated?

This article is from the issue dated March 18, 2010. An important element in the debate over health care reform concerns the level of future health care expenditures.

This Case Record is from the issue dated March 18, 2010, and deals with a 22-year-old woman with hypercalcemia and a pelvic mass.

This article summary is from the issue dated March 18, 2010. Over the past decade, limited attention has been paid to the human immunodeficiency virus (HIV) epidemic in the United States. The global epidemic — particularly the epidemic in sub-Saharan Africa, where approximately two thirds of the world's population living with AIDS resides — has rightfully received most of the focus. Meanwhile, however, the prevalence of HIV infection within some US populations now rivals that in some sub-Saharan African countries.

This article summary is from the issue dated March 10, 2010, and looks at the $1.1 billion-funded comparative-effectiveness research (CER) —unprecedented generosity for such a program.

Also in this summary: a study in which emangioma-derived stem cells showed vasculogenic activity in vivo when implanted into nude mice.

This summary covers the issue of March 11, 2010. Featured are articles on tumor-associated macrophages and survival in classic Hodgkin’s lymphoma, low diagnostic yield of coronary angiography, oral ivermectin versus malathion lotion for difficult-to-treat head lice, use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia, and ameliorating amyotrophic lateral sclerosis; a review article on commotio cordis; a case report of a man with peripheral neuropathy and ascites; and Perspective articles on the missing voice of patients in drug-safety reporting, on whether the states can nullify health care reform, and on health care volunteers and disaster response.

This article is from the issue dated March 11, 2010. Clinically relevant biomarkers for predicting the outcome of treatment in patients with Hodgkin's disease have not been established. In this study, gene profiling and immunohistochemical analysis were used to find such a marker. A strong association was found between a poor outcome of treatment and an increased number of CD68+ cells in the microenvironment of Reed–Sternberg cells. CD68, a marker of macrophages, outperformed the conventional International Prognostic Score and is available for immunohistochemical staining of diagnostic samples of Hodgkin's lymphoma.

This article is from the issue dated March 11, 2010. In this national registry of data on cardiac catheterization, only 38% of elective, diagnostic coronary angiograms showed obstructive lesions, and 39% of angiograms were interpreted as showing no disease. The findings indicate a relatively low diagnostic yield of elective coronary angiography, a procedure that exposes patients to substantial radiation.

This article is from the issue dated March 11, 2010. There are limited treatments for head lice. In this multicenter, cluster-randomized trial of 812 patients in 376 households, oral ivermectin was found to be superior to topical malathion lotion in eradicating head-lice infestation.

Also, the Images in Clinical Medicine shows red, puffy ears.

This article is from the issue dated March 11, 2010. Ventricular fibrillation and sudden death triggered by a blunt, nonpenetrating, and often innocent-appearing unintentional blow to the chest without damage to the ribs, sternum, or heart (in the absence of underlying cardiovascular disease) constitute an event known as commotio cordis. This review provides informationon the clinical profile of this event, the physiological mechanisms underlying it, and steps that can be taken to prevent the event and to resuscitate the victim, should it occur.

This article is from the issue dated March 11, 2010. This randomized, placebo-controlled, double-blind, multicenter trial assessed the safety and efficacy of the thyromimetic compound eprotirome in lowering the serum low-density lipoprotein cholesterol level in patients with hypercholesterolemia who were already receiving simvastatin or atorvastatin. Eprotirome was associated with decreased LDL levels in patients treated with statins.

This article is from the issue dated March 11, 2010. A 49-year-old man was admitted to this hospital because of ascites. During the past 4 years, paresthesias and weakness of the lower legs and hands had developed, followed by difficulty breathing, peripheral edema, and during the past year, blurred vision, optic-disk edema, and ascites. Imaging studies subsequently revealed retroperitoneal lymphadenopathy and lytic lesions in the tibia and sacrum. A diagnostic procedure was performed.

This Perspective article is from the issue dated March 11, 2010. The current drug-labeling practice for adverse events is based on the implicit assumption that an accurate portrait of patients' subjective experiences can be provided by clinicians' documentation alone. Yet a substantial body of evidence contradicts this.

This Perspective article is from the issue dated March 11, 2010. On February 1, the Virginia Senate passed a bill stating that "No resident of this Commonwealth . . . shall be required to obtain or maintain a policy of individual insurance coverage." In considering this legislation, Virginia joins numerous other states with pending legislation aimed at limiting, changing, or opposing national health care reforms. What is going on here?

This Perspective article is from the issue dated March 11, 2010. It provides an overview for healthcare providers on how to help in a crisis, such as the one in Haiti following the earthquake in February. 

This article summary is from the issue dated March 11, 2010. A newly implicated molecular pathway in skeletal muscle regulates the formation of the neuromuscular junction and is implicated in a mouse model of amyotrophic lateral sclerosis.

This summary covers the issue of March 4, 2010. Featured are articles on dopamine vs. norepinephrine for shock; ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy; glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults; pneumococcal conjugate vaccine in HIV-infected adults; and the collection of data on patients’ race and ethnic group; a review article on the management of varices and variceal hemorrhage in cirrhosis; a Clinical Problem-Solving article on stalking the diagnosis; and Perspective articles on Partners in Health and the Haitian earthquake, on Medicare’s opportunity to encourage innovation in health care delivery, and on the FDA’s review of a new antidiabetic therapy.

This article is from the issue dated March 4, 2010. In this randomized trial of three common treatments for childhood absence epilepsy, ethosuximide and valproic acid were more effective than lamotrigine, and adverse effects on attention were less frequent with ethosuximide than with valproic acid. These findings suggest that ethosuximide has the best efficacy and safety profile.

In addition, there is a related editorial regarding the efficacy of new therapies.

In this comparative-effectiveness trial, there was no significant difference in the overall survival rate between patients with shock who were treated with dopamine and those who were treated with norepinephrine. However, dopamine was associated with more cardiac arrhythmias and with a higher mortality rate among patients with cardiogenic shock.

There is also a related editorial.

This article is from the issue dated March 4, 2010. Pneumococcal infection is an important cause of death and complications in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. In this placebo-controlled, randomized trial involving 496 predominantly HIV-infected Malawian adults who had recently had an invasive pneumococcal infection, the 7-valent conjugated pneumococcal vaccine was found to have 74%efficacy in preventing subsequent invasive pneumococcal infection with a vaccine-associated serotype.

This article is from the issue dated March 4, 2010. Gastroesophageal varices are present at diagnosis in almost half of patients with cirrhosis, and variceal hemorrhage continues to be a lethal complication of cirrhosis. This review explains the three main challenges in clinical management: primary prophylaxis to prevent a first episode of hemorrhage, the treatment of acute bleeding episodes, and secondary prophylaxis to prevent recurrence of variceal hemorrhage.

This article is from the issue dated March 4, 2010. This community-based study of nondiabetic adults compared the prognostic value of glycated hemoglobin and fasting glucose for identifying persons at risk for clinical outcomes such as diabetes. As compared with fasting glucose, glycated hemoglobin was similarly associated with the risk of diabetes and morestrongly associated with the risks of cardiovascular disease and death from any cause, adding to data about the use of glycated hemoglobin as a diagnostic measure.

This Sounding Board article is from the issue dated March 4, 2010. The authors argue that physician practices should routinely collect data on the race and ethnic group of their patients. They caution against the use of these data to infer information about health-related values or beliefs, and they discuss the benefit of using these data at the population level to detect disparities in care and to improve the quality of care.

This Perspective article by author Tracy Kidder is from the issue dated March 4, 2010. The earthquake of January 12 killed many of Haiti's doctors and nurses and destroyed a large part of the country's medical infrastructure. But Zanmi Lasante (ZL), the Haitian branch of Partners in Health (PIH), was left intact. ZL had been the largest health care provider in rural Haiti. After the quake, it became (temporarily, at least) the largest and one of the most important in the entire country.

This Clinical Problem-Solving article is from the issue dated March 4, 2010. A 58-year-old woman presented to her primary care physician after several days of dizziness, anorexia, dry mouth, increased thirst, and frequent urination. She had also had a fever and reported that food would "get stuck" when she was swallowing. She reported no pain in her abdomen, back, or flank and no cough,shortness of breath, diarrhea, or dysuria.

This article is from the issue dated March 4, 2010. Although many antidiabetic therapies have been approved by the Food and Drug Administration (FDA), new therapies are needed to achieve glycemic goals, because beta-cell function declines over time in patients with diabetes. On January 25, 2010, the FDA approved liraglutide, a glucagon-like-peptide-1 (GLP-1) receptor agonist.

This article Perspective article is from the issue dated March 4. 2010. Whatever the fate of current reform proposals, Congress cannot avoid important decisions about Medicare. Without new legislation, Medicare payments to physicians are scheduled to be cut by 21% on March 1, 2010, and the Hospital Insurance Trust Fund will become insolvent by 2013.

Also, Images in Clinical Medicine.

This summary covers the issue of February 25, 2010. Featured are articles on genetic associations with stuttering, lasofoxifene and osteoporosis, timing of initiation of antiretroviral drugs during tuberculosis therapy, an algorithm for tuberculosis screening and diagnosis in people with HIV, and wrestling with BRCA1; review articles on permethrin and ivermectin for scabies and on Graves’ ophthalmopathy; a case report of a man with a lesion on the tongue; and Perspective articles on conflicts of interest in academic medicine, on avoiding side effects in implementing health insurance reform, and on risking big changes with small reforms.

This article is from the issue dated February 25, 2010. This study shows that variants of proteins that indirectly guide hydrolases to the lysosome are associated with stuttering. The authors analyzed genes at a locus previously implicated in stuttering and identified mutations affecting a subunit of GlcNAc-phosphotransferase and changes in genes encoding other proteins in the same enzyme complex or pathway. This unexpected finding implies a metabolicpathway in susceptibility to stuttering.

This article is from the issue dated February 25, 2010. Women between 59 and 80 years of age with a bone mineral density T score of –2.5 or less at the femoral neck or spine received the selective estrogen-receptor modulator lasofoxifene (either 0.25 or 0.5 mg daily) or placebo for 5 years. Lasofoxifene was associated with lower risks of fractures, estrogen-receptor–positive breast cancer, coronary heart disease, and stroke, with no increase in endometrial cancer, but there was an increase in venous thromboembolicevents.

This article is from the issue dated February 25, 2010. The optimal timing for the initiation of antiretroviral therapy in patients with both human immunodeficiency virus infection and tuberculosis is unclear. This open-label study involves 642 such patients who received antiretroviral therapy initiated either during or after the completion of tuberculosis therapy. The initiation of antiretroviral therapy during tuberculosis therapy was associated with a relative reduction of 56% in the rate of death.

This article is from the issue dated February 25, 2010. Efficient, economical screening for active tuberculosis in resource-poorenvironments is a challenge. Screening is particularly important when there is coinfection with human immunodeficiency virus (HIV) and therefore concomitant consideration of initiation of antiretroviral therapy and the risk of the immune reconstitution syndrome. In this study of 1748 patients in Cambodia, Thailand,and Vietnam who were infected with HIV, an assessment for the presence of one of three symptoms — cough, fever, or night sweats — for more than 21 days over the preceding 4 weeks was found to have 93% sensitivity and 36% specificity for the detection of active tuberculosis infection.

Additionally, Stuart M. Butler, PhD, writes an editorial entitled, "Risking Big Changes with Small Reforms," in which he argues that seemingly modest changes in terms of healthcare reform could unleash huge pressures that would profoundly alter the system's future structure and function.

This article reviews the mechanisms that lead to the development of Graves' ophthalmopathy. A central feature in its development is autoimmunity that involves not only T cells, B cells, and macrophages but also fibroblasts and adipose tissue within the orbit. Intraorbital cytokine-mediated inflammation also has a prominent role. These recent findings suggest new ways of treating this debilitating disease.

This Case Record of the Massachusetts General Hopsital is from the issue dated February 25, 2010. A 37-year-old man was seen in the oral and maxillofacial surgery clinic because of a painful lesion on the tongue. On examination, there was a tender, irregular, shallow ulcer on the left ventral surface of the tongue and a mobile, smooth, tender lymph node in the left anterior cervical chain. Scattered areas of erythemaand blisters were present on the lower legs.

This Perspective article is from the issue dated February 25, 2010. Relationships between academia and industry have both benefits and risks. Close collaboration between academia and industry has facilitated the development of many new drugs. This is an area in which key interests may be aligned: the public seeks effective new therapies, academia wishes to translate basic discoveries into treatments, and industry wishes to develop new products.

This Perspectives article is from the issue dated February 25, 2010. US health insurance reform proposals currently being discussed include changes in the way insurers treat some people with above-average health risks. Without such "risk rating" and coverage exclusions, insurers would be subject to substantial adverse selection. Given the tradeoffs, how should legislation on these matters be designed, and can they be made to work better?

This article is from the issue dated February 25, 2010. It begins with a case vignette regarding a four-year-old boy who is brought to a health center with sores on his arms and legs. He and several siblings receive a diagnosis of scabies. Crusted scabies is diagnosed in an elderly aunt in the same household.

This Clinical Implications of Basic Research article is from the issue dated February 25, 2010. More than 200,000 women in the United States carry an abnormal version of the breast-cancer susceptibility gene BRCA1, and unraveling how mutations in this gene lead to breast cancer is a major task.

Also: Images in Clinical Medicine.

This summary covers the issue of February 18, 2010. Featured are articles on the willful modulation of brain activity in disorders of consciousness, projected effect of dietary salt reductions on future cardiovascular disease, dose of prophylactic platelet transfusions and prevention of hemorrhage, and newborn-care training and perinatal mortality in developing countries; a review article on the small renal mass; a case report of a man with HIV infection, proteinuria, and edema; and Perspective articles on the debate over regional variation in health care spending and on the earthquake in Haiti.

This article is from the issue dated February 18, 2010. In this study involving 54 patients in a vegetative or minimally conscious state, the use of functional magnetic resonance imaging (MRI) to assess responses during mental-imagery tasks showed that 5 patients were able to willfully modulate their brain activation. These findings suggest that functional MRI can be used to demonstrate evidence of awareness and cognition that cannot be detected by means of clinical assessment.

Allan H. Ropper, MD, writes a related editorial, "Cogito Ergo Sum by MRI."

This article is from the issue dated February 18, 2010. The salt intake of the U.S. population is rising. Using the Coronary Heart Disease Policy Model, these investigators found that a reduction in salt intake of 3 g per day would result in substantial reductions in the incidence of coronary heart disease, stroke, and death. A more modest reduction of 1 g per day would also have public health benefits. The reduction of salt intake is an important goal for the country.

Also, Lawrence J. Appel, MD, MPH, and Cheryl A.M. Anderson, PhD, MPH, author the related editorial, "Compelling Evidence for Public Health Action to Reduce Salt Intake."

This article is from the issue dated February 18. 2010. The use of platelet transfusions to prevent bleeding in patients with thrombocytopenia due to chemotherapy or other causes of marrow suppression is widespread, but the optimal number (dose) of platelets is unsettled. In this randomized trial, three doses of platelets were studied: the usual dose, half the usual dose, and twice the usual dose. No major differences in bleeding complications were found among the three groups, but more transfusions weregiven in the lowest-dose group to prevent bleeding.

Also, Images in Clinical Medicine.

This article is from the issue dated February 18, 2010. Training community-based birth attendants in rural communities in developing countries in the Essential Newborn Care program (routine care and resuscitation) was not associated with a reduction in the rate of neonatal death in the 7 days after birth, but the rate of stillbirth was significantly reduced. In a subsequentcluster-randomized trial, training in the Neonatal Resuscitation Program (more advanced resuscitation training) did not significantly reduce rates of neonatal death or stillbirth.

This article is from the issue dated February 18, 2010. A 65-year-old man with a history of well-controlled hypertension presents for a follow-up visit after an incidental finding of a small mass in the right kidney on an abdominal computed tomographic scan (ordered to evaluate lower-quadrant pain, which has since resolved). The mass is 3.2 cm, anterior, heterogeneous, andsolid, and is in the right renal hilum near the main renal artery, vein, and ureter; the left kidney appears normal. The patient feels well, his physical examination is unremarkable. His serum creatinine level is 1.2 mg per deciliter. How should this patient be further evaluated and treated?

This article is from the issue dated February 18, 2010. In this Case Record of the Massachusetts General Hospital, a 51-year-old man with human immunodeficiency virus and hepatitis C virus infections presented with proteinuria, edema, and worsening hypertension. He had obesity, hyperlipidemia, obstructive sleep apnea, and a history of hypertension and coronary artery disease. He had recently taken nonsteroidal antiinflammatory drugs for joint pain. A diagnostic procedure was performed.

This Perspective article is from the issue dated February 18, 2010. The regional variations in health care spending that are documented by the Dartmouth Atlas of Health Care have been cited by many as a justification, and possible basis, for changes in provider payment rates. This article addresses various concerns about the Dartmouth data.

This Perspective article is from the issue dated February 18, 2010. At 4:53 p.m. on Tuesday, January 12, an earthquake killed or gravely injured hundreds of thousands of people in Port-au-Prince,Haiti. Even more were left homeless. The devastation is incomprehensible. Chaos followed, since the centers of law, order, and functioning society were destroyed or suffered severe losses.

This article is from the issue dated February 18, 2010. The recent Senate election in Massachusetts may reshape or delay healthcare reform, but we still face the twin challenges ofunsustainable cost increases and uneven quality that plague US health care.

This summary covers the issue dated February 11, 2010. Featured are articles on childhood obesity, other cardiovascular risk factors, and premature death; stent graft versus balloon angioplasty for failing dialysis-access grafts; single-dose liposomal amphotericin B for visceral leishmaniasis in India; long-term results of hypofractionated radiation therapy for breast cancer; lack of cyclophilin B in osteogenesis imperfecta; and innate immunity and HIV; a review article on the enigma of spontaneous preterm birth; a case report of a man with arthralgias, oral ulcers, vision loss, and vocal-cord paralysis; and Perspective articles on performing futile CPR, on failing to thrive, and on the constitutionality of the individual mandate for health insurance.

Also, nejm.org offers a new interactive feature, entitled Stalking the Diagnosis,

This article is from the issue dated February 11, 2010. This study examined body-mass index, glucose tolerance, blood pressure, and cholesterol levels in American Indian children without diabetes who were then followed to adulthood. Obesity, glucose intolerance, and hypertension in childhood were strongly associated with premature death from endogenous causes, whereas hypercholesterolemia was not.

Also, Edward W. Gregg, PhD, writes an accompanying editorial.

This article is from the issue dated February 11, 2010. In this randomized, multicenter trial, patients with a venous anastomotic stenosis who were undergoing hemodialysis were assigned to undergo balloon angioplasty or placement of a stent graft. Primary end points included patency of the treatment area and patency of the entire vascular access circuit. Percutaneous revision was improved with the use of a stent graft, which appeared to provide durable and superior patency and freedom from repeatinterventions.

This article is from the issue dated February 11, 2010. The world's preterm birth rate continues to increase. In 2006, preterm births accounted for 12.8% of live births in the United States. Only about half the cases of prematurity result from identifiable causes. This review discusses the challenge of understanding the causes of premature birth and finding ways to prevent it.

Also, Drs. Robert K. Kerlan, Jr. and Jeanne M. LaBerge write an editorial, entitled "Fistula First, Stent Graft Second," accompanying the original article, "Stent Graft versus Balloon Angioplasty for Failing Dialysis-Access Grafts."

This Perspective article is from the issue dated February 11, 2010. Once President Barack Obama and Democrats in Congress have passed a health care reform bill, conservative groups are likely to challenge parts of it as unconstitutional, arguing that it oversteps Congress's powers. A key target will be the individual mandate, which is designed to coax uninsured persons into purchasing insurance.

This Images in Clinical Medicine is from the issue dated February 11, 2010.

Also, an original article describes a randomized, multicenter trial, patients with a venous anastomotic stenosis who were undergoing hemodialysis were assigned to undergo balloon angioplasty or placement of a stent graft. Primary end points included patency of the treatment area and patency of the entire vascular access circuit. Percutaneous revision was improved with the use of a stent graft, which appeared to provide durable and superior patency and freedom from repeatinterventions.

This Case Record is from the issue dated February 11, 2010. The patient had been well until 19 months before presentation, when he awoke with severe joint pain. On examination by his internist 1 month later, there was incomplete fist closure and decreased extension of the right elbow, without joint deformities or synovial swelling. Serum levels of electrolytes, bilirubin, calcium, thyrotropin, creatine kinase, C-reactive protein, and uric acid; the erythrocyte sedimentation rate; and tests of renal and liver function were normal.

This Clinical Implications of Basic Research article is from the issue dated February 11, 2010. Tetherin, a native cellular molecule, opposes the egress of human immunodeficiency virus (HIV) virions from the infected cell. It achieves this by literally tethering the budding virion to the cell surface.

This article is from the issue dated February 11, 2010. The author writes that she and her mother and were on vacation in New York when they got a call from her aunt and uncle, both psychiatrists, in Portland, Oregon. The author's 90-year-old, demented paternal grandmother seemed to be having a stroke. They wanted to know whether they should take her to the emergency room.

This Perspective article is from the issue dated February 11, 2010. Although there is currently much debate about the types of care to which patients are entitled, one thing on which everyone can agree is that nonbeneficial care should be eliminated. Although such care can be hard to define, in some circumstances experienced clinicians can be virtually certain that attempts at resuscitation will fail. In these cases, many argue that hospitals should adopt policies that allow physicians to refuse when families demand futile cardiopulmonary resuscitation (CPR).

This article is from the issue dated February 11, 2010. Osteogenesis imperfecta is a heritable disorder that causes bone fragility. The authors describe two siblings with a mutation in the peptidyl-prolyl isomerase B gene (PPIB), resulting in the absence of cyclophilin B. Collagen folding and prolyl 3-hydroxylation in the proband were normal.

This article is from the issue dated February 11, 2010. The optimal schedule of radiation treatment after breast-conserving surgery for invasive breast cancer is unknown. In this study, two groups of patients received either hypofractionated radiation or a standard schedule of radiation treatment. Ten years later, the two groups had similar risks of local recurrence and a similarappearance of the breast.

This summary covers the issue of February 4, 2010. Featured are articles on a placebo-controlled study of oral fingolimod in relapsing multiple sclerosis, oral fingolimod or intramuscular interferon for relapsing multiple sclerosis, cladribine or placebo for relapsing multiple sclerosis, acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2, and comparative effectiveness and health care spending; a review article on jet lag; a Clinical Problem-Solving article describing a woman with dyspnea; and Perspective articles on Medicare and medical technology, on withholding information from patients, and on launching HITECH.

This article summary is from the issue dated February 4, 2010. In this 24-month, randomized trial involving patients with relapsing–remitting multiple sclerosis, oral fingolimod reduced the rates of relapse and disability progression, as compared with placebo. Adverse events reported in patients treated with fingolimod included bradycardia, atrioventricular conduction block, macular edema, elevations in liver-enzyme levels, and mild hypertension.

This article is from the issue dated February 4, 2010. In this 12-month trial involving patients with relapsing–remitting multiple sclerosis, oral fingolimod was more effective than intramuscular interferon beta-1a in reducing relapse rates. Adverse events associated with fingolimod included herpesvirus infections (two fatal infections), atrioventricular block, macularedema, skin cancer, and liver-enzyme elevation.

This article is from the issue dated February 4, 2010. In this 96-week, placebo-controlled trial, oral cladribine reduced relapse rates and lowered the risk of sustained disability in patients with relapsing–remitting multiple sclerosis. Patients who were treated with cladribine had large reductionsin lymphocyte counts and more infections, including herpes zoster and one death from reactivation of tuberculosis.

Also, William M. Carroll, MD, writes an accompanying editorial entitled "Oral Therapy for Multiple Sclerosis — Sea Change or Incremental Step?"

This article is from the issue dated February 4, 2010. This Clinical Practice article looks at a 55-year-old physician planning a trip from Los Angeles to London to attend a scientific conference. His previous trip to Europe was complicated by sleepiness during meetings and difficulty falling asleep and remaining asleep at night. He wants to know what he can do to avoid jet lag. What would you advise?

These Images in Clinical Medicine and Clinical Problem Solving Article are from the issue dated February 4, 2010.

This Sounding Board article is from the issue dated February 4, 2010. The authors argue that healthcare costs can be reduced without a negative effect on quality by reducing spending on interventions that are not cost-effective.

This Perspective article, examining several critical steps recently taken by the government toward a nationwide, interoperable, private, and secure electronic health information system, is from the issue dated February 4, 2010.

This article is from the issue dated February 4, 2010. Suppressive therapy for herpes simplex virus 2 (HSV-2) has also been shown to reduce the levels of human immunodeficiency virus type 1 (HIV-1). However, in this placebo-controlled trial involving 3408 African couples who were discordant in serologic status for these two viruses, daily treatment with acyclovir did notreduce the frequency of HIV-1 transmission, despite a reduction in HIV-1 RNA levels and a 73% reduction in the occurrence of HSV-2–positive genital ulcers.

This Perspective article is from the issue dated February 4, 2010. In deciding whether to pay for new medical technologies, the Centers for Medicare and Medicaid Services (CMS) is becoming more specific about its requirements for evidence of improved health outcomes in the Medicare population. These authors argue this is a positive and overdue step, but one whose rationale and likely consequences must be better understood by the medical community, policymakers, and the public.

This Perspective article is from the issue dated February 4, 2010. The authors write that, as clinicians who strongly value truth telling and active patient involvement in medical decision making, they have  been reflecting on the circumstances in which physicians consciously (and sometimes unconsciously) withhold from patients information about their conditions, treatments, and outcomes.

This summary covers the issue of January 28, 2010. Featured are articles on rotavirus vaccine and severe gastroenteritis in African infants, effect of rotavirus vaccine on death from childhood diarrhea in Mexico, outcomes after internal versus external tocodynamometry for monitoring labor, vaccine-acquired rotavirus in infants with severe combined immunodeficiency, increased ambulatory care copayments and hospitalizations among the elderly, and insight into insulin secretion; a review article on Alzheimer’s disease; a case report of an infant with developmental delay and irritability; and Perspective articles on tobacco control and free speech, on medicine’s ethical responsibility for health care reform, and on American values and health care reform.

This article is from the issue dated January 28, 2010. Rotavirus is the leading cause of gastroenteritis in children worldwide. In this report, the efficacy of the rotavirus vaccine among 4417 children in Malawi and South Africa was studied in a randomized trial. Severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group as compared with 1.9% of the infants in the pooled vaccine group; the vaccine efficacy was 61.2%.

These articles are from the issue dated January 28, 2010. Rotavirus remains an important cause of diarrhea-related death and complications worldwide. Implementation of rotavirus vaccination in Mexico since late 2007 has been associated with a relative reduction of 35% in diarrhea-related mortality in children under 5 years of age, with the greatest decrease found in infants 11 months of age or younger, the age group that was eligible to receive vaccination.

In a second article looks at the case of rotaviral infection in three children who were vaccinated before they were found to have severe combined immunodeficiency, thus raising concern regarding the safety of this live attenuated vaccine in severely immunocompromised persons.

This article summary is from the issue dated January 28, 2010. In this comparison of Medicare plans that increased copayments for ambulatory care visits with plans that did not, higher copayments were associated with fewer outpatient visits and more hospitalizations. The higher copayments may have resulted in preventable hospital admissions and increased the overall cost of care.

Also, Dr. Mathuram Santosham writes an editorial on the effects of the rotavirus vaccine on childhood diarrhea, which results in over half a million deaths each year in both developed and developing countries.

This article is from the issue January 28, 2009. In this multicenter, randomized trial, internal tocodynamometry was compared with external monitoring of uterine activity in women with induced or augmented labor. The use of internal tocodynamometry did not reduce the rate of operative deliveries or improve other maternal or neonatal outcomes.

Also: two cases from Images in Clinical Medicine.

In this case record, from the issue dated January 28, 2010, a 4.5-month-old boy was seen in the pediatric neurology clinic of this hospital because of developmental delay and irritability.

This article is from the issue dated January 28, 2010. This review of Alzheimer's disease assembles a variety of findings relevant to the mechanism of the disease and ties them together using the current understanding of the basis of the loss of cognition: the accumulation of misfolded proteins, which cause oxidative and inflammatory damage to the brain and, ultimately, synaptic dysfunction.

This article is from the issue dated January 28, 2010. On June 22, 2009, President Barack Obama signed the Family Smoking Prevention and Tobacco Control Act. This landmark legislation, which passed the House by a vote of 307 to 97 and the Senate 79 to 17, grants the Food and Drug Administration (FDA) extensive authority to regulate tobacco products. Even before the legislation was passed, the extent to which it would be challenged by industry and proponents of stringent First Amendment protections for advertising was signaled by a letter to senators from the American Civil Liberties Union (ACLU).

This article summary is from the issue dated January 28, 2010. With the national debate over health care reform careening between tired, well-rehearsed talking points, on the one hand, and deep-in-the-weedsdebates over technical details, initiatives, and financing mechanisms, on the other, many people find themselves feeling frustrated and left out of the conversation. Yet most thoughtful Americans would have something meaningful to say about the values we should choose for the foundation of our system of health care. And by focusing on these fundamental considerations, perhaps we can deepen and broaden the discussion of values and public policy.

This summary covers the issue of January 21, 2010. Featured are articles on treatment with monoclonal antibodies against Clostridium difficile infection, skeletal dysplasia and the Golgi apparatus, and left ventricular filling in emphysema and airflow obstruction; review articles on systolic heart failure and on Williams–Beuren syndrome; a case report of a man with abdominal and flank pain; and Perspective articles on erythropoiesis-stimulating agents and on accelerating the use of electronic health records in physician practices.

This article is from the issue dated January 21, 2010. In patients with C. difficile infection, treatment with monoclonal antibodies against C. difficile toxins A and B, in addition to metronidazole or vancomycin, reduced the rate of recurrence of infection, as compared with placebo (7% vs. 25%).

This article is from the issue dated January 21, 2010. A form of skeletal dysplasia in mice is caused by a mutation in a gene that is critical for the functioning of the Golgi apparatus. A mutation in the orthologous gene in humans results in a similar phenotype: achondrogenesis type 1A.

This article is from the issue dated January 21, 2010. This review focuses on the recommended treatment for ambulatory patients with systolic heart failure; heart failure with preservedejection fraction was reviewed previously in this series.

And, an Editorial by Hudson H. Freeze, PhD.

This article is from the issue dated January 21, 1010. Williams–Beuren syndrome, a multisystem disorder caused by the deletion of a chromosome region of 1.5 million to 1.8 million base pairs containing 26 to 28 genes, is a disorder of microdeletion or contiguous gene deletion. This review covers current understanding of the biology of this disorder.

This Perspective article is from the issue dated January 21, 2010. Randomized trials have endeavored to show that using ESAs to raise hemoglobin concentrations to higher targets improves clinical outcomes in patients with anemia associated with chronic kidney disease. Dr. Ellis Unger and FDA colleagues describe the trial results, which have suggested the opposite.

The Editorial, "The Shrinking Heart in Chronic Obstructive Pulmonary Disease," is by Dr. Anton Vonk-Noordegraaf.

This article is from the issue dated January 21, 2010. The patient was in his usual state of health until 5 weeks before admission, when diffuse abdominal pain developed, most severein the lower right quadrant and radiating to the right side and back; it decreased slightly with leaning forward, increased with other movements, including walking, and prevented him from sleeping. He went to an urgent care clinic at a health center affiliated with this hospital.

This article is from the issue dated January 21, 2010. North Shore Hospital System on Long Island in New York recently announced that it will pay an incentive of up to $40,000 to each physician in its network who adopts its electronic health record (EHR) — paying 50% of the cost to physicians who install an EHR that communicates with the hospital and 85% of the cost if the physician also shares de-identified data on the quality of care.

These Images in Clinical Medicine are from the issue dated January 21, 2010. 

Also, an original article examines the hypothesis that emphysema, as detected on computed tomography (CT), and airflow obstruction are inversely related to left ventricular end-diastolic volume, stroke volume, and cardiac output among persons without very severe lung disease.

Featured are articles on the use of mental health services among U.S. Army wives, morphine use after combat injury in Iraq and PTSD, ustekinumab versus etanercept for moderate-to-severe psoriasis, preoperative biliary drainage for pancreatic cancer, tracheal allotransplantation after withdrawal of immunosuppressive therapy, and progenitor cells of prostate cancer; a review article on nosocomial bacterial meningitis; a case report of a man with hypertension, hyperglycemia, and edema; and Perspective articles on “play-or-pay” insurance reforms for employers, on uncomfortable arithmetic and expanding health insurance coverage, and on measuring the performance of the U.S. health care system.

This article is from the issue dated January 14, 2010. In this study of injured U.S. military personnel, the use of morphine during trauma care was associated with a reduced risk of post-traumatic stress disorder (PTSD) after injury. This finding suggests that optimal control of pain after serious injury may help prevent PTSD.

This article is from the issue dated January 14, 2010. In this study involving wives of active-duty U.S. Army soldiers, women whose husbands were deployed to Iraq or Afghanistan between 2003 and 2006 were more likely to receive diagnoses of depressive, sleep, anxiety, and stress disorders than were women whose husbands were not deployed.

This article is from the issue dated January 14, 2010. In this 12-week randomized trial comparing two biologic agent known to be effective for psoriasis, ustekinumab (an interleukin-12 and interleukin-23 blocker) was more effective than etanercept (an inhibitor of tumor necrosis factor ). Adverse events associated with the two treatments were similar, but the trial was not large enough and follow-up was not long enough to assess uncommonadverse events.

Also, an editorial by Drs. Todd H. Baron and Richard A. Kozarek, counsels caution on the use of preoperative biliary stents in pancreatic cancer.

This article is from the issue dated January 14, 2010. A donor trachea, harvested from a cadaver, was transplanted into the forearm of a recipient and wrapped in the recipient's fascia.

Also, Dr. Megan Sykes writes an editorial on the aforementioned article. 

This article is from the issue dated January 14, 2010. Nosocomial bacterial meningitis is most often related to either complicated head trauma or invasive procedures, such as craniotomy, placement of ventricular catheters, intrathecal infusion of medications, or spinal anesthesia. In addition, metastatic infection from hospital-acquired bacteremia occasionally leads to meningitis.

Also, Matthew J. Friedman, MD, PhD, writes an editorial on the search for a "morning-after pill" following exposure to traumatic stress and the relationship between the deployment of military personnel and the mental health of their spouses.

In this Case Record of the Massachusetts General Hospital, a 75-year-old man was admitted to this hospital because of the recent onset of hypertension, hyperglycemia, and edema.

This article is from the issue dated January 14, 2010. This Perspective article is by Bradley Herring, PhD and Mark V. Pauly, PhD. The authors focus on one prominent feature of the current health care reform bills — the "play-or-pay" rule for employers: workers must receive part of their compensation in the form of employer-sponsored health insurance, or the company's payroll will be subjected to a tax penalty.

This article is from the issue dated January 14, 2010. In this Perspective article, Katherine Baicker, PhD, and Amitabh Chandra, PhD, discuss the debate about expanding health insurance coverage — much of which, they say, avoids addressing an uncomfortable trade-off: with a limited budget, making benefits more generous means being able to cover fewer people. Moreover, designing insurance benefitsthat are limited to coverage of higher-value care but are extended to more people will generate greater improvements in healththan providing unlimited care for fewer people.

Also, a Clinical Implications of Basic Research article looks at prostate cancer and a subgroup of luminal cells in the prostate gland of the mouse that are resistant to apoptosis induced by androgen withdrawal and can be induced to form carcinomas.

This Perspective article is from the issue dated January 14, 2009. Evidence that other countries perform better than the United States in ensuring the health of their populations is a sure prod to the reformist impulse. The World Health Report 2000, Health Systems: Improving Performance, ranked the US healthcare system 37th in the world;— a result that has been discussed frequently during the current debate on US healthcare reform.

These Images in Clinical Medicine are from the issue dated January 14, 2010. They cover cases of generalized ostraceous psoriasis and postoperative tracheal stenosis.

Also, an original article covers a multicenter, randomized trial, in which preoperative biliary drainage was compared with surgery alone for patients with cancer of the pancreatic head.

This summary covers the issue of January 7, 2010. Featured are articles on preventing surgical-site infections in nasal carriers of S. aureus, chlorhexidine–alcohol for surgical-site antisepsis, severe 2009 H1N1 influenza in pregnant and postpartum women, variants of DENND1B and asthma in children, and pediatric hospitalizations associated with 2009 H1N1 influenza in Argentina; a review article on stage IV chronic kidney disease; a Clinical Problem-Solving article describing painful purple toes; and Perspective articles on ensuring the fiscal sustainability of health care reform, on payment reform and the need to harmonize approaches in Medicare and the private sector, and on what physicians can learn from online rating sites.

This article is from the issue dated January 7, 2010. In a randomized trial, eradication of colonization with S. aureus by rapid screening at admission and subsequent decolonization (with intranasal mupirocin and chlorhexidine skin washes) were associated with a decrease in postoperative surgical-site infections.

Both articles are from the issue dated January 7, 2010. This study analyzed data reported for 239 women of reproductive age who were hospitalized with 2009 H1N1 influenza; 94 were pregnant, and 8 were postpartum. Infection with the 2009 H1N1 virus can cause significant morbidity and mortality in pregnant and postpartum women.

Also, Dr. Richard P. Wenzel writes an Editorial on minimizing surgical-site infections.

This article is from the issue dated January 7, 2010. A 57-year-old man presented to the emergency department with painful purple discoloration of three toes on his left foot. He had also had intermittent blurry vision, chest pain, fatigue, anorexia, drenching night sweats, and a weight loss of 7 kg (15 lb) over the previous 3 weeks.

This article is from the issue dated January 7, 2010. Peter Lee and colleagues argue that the harmonization of payment models would require a few simple steps that build on the revision of fee-for-service payments to reflect services’ value for patients.

This article is from the issue dated January 7, 2010. After reading physician-rating sites, Dr. Shaili Jain is reassured that what patients want from their physicians is not all that different from what good physicians want to offer their patients.

This article is from the issue dated January 7, 2010. Michael Chernew and colleagues write that the historical flow of valuable but costly medical advances raises a profound question: can that flow be maintained in future years without rates of spending increase that wreak economic havoc?

These articles are from the issue dated January 7, 2010. The preoperative application of chlorhexidine–alcohol was found to be a more effective skin preparation than povidone–iodine for preventing incisional infections.

Also, during the winter (May through July 2009) in Buenos Aires, the death rate associated with 2009 H1N1 influenza in children was 10 times that associated with seasonal influenza in 2007.

This summary covers two Images in Clinical Medicine, from the issue dated January 7, 2010.

Featured in this issue are articles on MMP12, lung function, and COPD in high-risk populations; genetic susceptibility to infection by Mycobacterium leprae; household transmission of 2009 H1N1 influenza; outbreak of 2009 H1N1 influenza at a New York City school; public reporting of discharge planning and rates of readmissions; and molecular control of age-related diseases; a review article on activated protein C for sepsis; a case report of a boy with hypothermia and frostbite; and Perspective articles on abortion politics and health insurance reform, on Australia’s winter with the 2009 pandemic influenza A (H1N1) virus, on the emotional epidemiology of H1N1 influenza vaccination, and on industry influence on comparative-effectiveness research funded through health care reform.

These articles are from the issue dated December 31, 2009. A variant of MMP12 is associated with increased lung function in children with asthma and in adult smokers. It is also associated with a decreased risk of chronic obstructive pulmonary disease in adult smokers.

Also, a study on leprosy implicates variation in genes encoding molecules in the NOD2 signaling pathway (which regulates innate immunity) in susceptibility to infection with Mycobacterium leprae and leprosy. An editorial by Erwin Schurr, PhD, accompanies this article.

This article is from the issue dated December 31, 2009. This study shows that when a member of the household became infected with the 2009 H1N1 influenza virus, household contacts less than 18 years of age were twice as susceptible to an acute respiratory illness as were those 19 to 50 years of age, whereas contacts older than 50 years were less susceptible.

This article is from the issue dated December 31, 2009. Health policy experts are focusing on the prevention of hospital readmissions as a way to improve quality and reduce costs. This study showed wide variation in hospital readmission rates but only a weak association between discharge planning and readmission.

This Case Study is from the issue dated December 31, 2009. A 16-year-old boy was admitted to the hospital after being found unconscious in a snowbank at 6 a.m. on New Year’s Day, approximately 7 hours after leaving a party at which alcohol was being served. The rectal temperature was 31.3°C. Both hands and the right foot were cold and hard to palpation; the left foot was cold but soft.

This Clinical Implications of Basic Research article is from the issue dated December 31, 2009. Recent discoveries in the research on aging suggest that modern science is more adept at keeping aging at bay — at least temporarily and thus far only in worms, flies, and rodents  — than at halting it completely. A recent study has identified ribosomal protein S6 kinase 1 (S6K1) as a molecular player in the aging game.

These two articles are from the issue December 31, 2009. In the first, a 55-year-old man presents with a small-bowel perforation, and sepsis develops. Treatment with recombinant human activated protein C is recommended. The clinical benefit and recommendations for use of recombinant human activated protein C are controversial.

Second, an editorial looks at accumulating evidence of common pathogenetic pathways in asthma and COPD.

This article is from the issue dated December 31, 2009. Dr. Danielle Ofri describes the fascinating and frustrating shift in public sentiment over the course of the H1N1 epidemic.

This article summary is from the issue dated December 31, 2009. Dr. James Bishop and colleagues write that key lessons from Australia’s experience with the spread of H1N1 suggest that important elements of a response were a national coordination of efforts and the use and modification of a national pandemic plan framework.

Also in this summary: Images in Clinical Medicine.

This Perspective article is from the issue dated December 31, 2009. The centrality of abortion in US politics makes it likely that abortion funding will play a major role in determining whether there is any health care reform law at all. George Annas describes the Stupak amendment and the current state of the law on federal funding for abortion.

This article is from the issue dated December 31, 2009. The Senate Finance Committee’s healthcare reform bill would mandate industry involvement in the oversight of comparative-effectiveness research. Drs. Harry Selker and Alastair Wood make a case for the independence of the scientific process.

This summary covers the issue dated December 24, 2009. Featured are articles on the clinical features of the initial cases of 2009 H1N1 virus infection in China, genetic variants associated with Lp(a) lipoprotein level and coronary disease, long-term outcome associated with early repolarization, and a sensitive troponin T assay in stable coronary artery disease; a review article on Barrett’s esophagus; a case report of a man with fever and respiratory failure; and Perspective articles on getting the facts straight on healthcare reform, on screening mammography, and on cervical-cancer screening.

In China an initial policy of quarantine was instituted and early cases of H1N1 were systematically monitored. In these early cases, the incubation period was 2 days, 67.4% of the patients had fever, and the duration of viral shedding was 6 days.

These Editorials are from the issue dated December 24, 2009.

Dr. Nicole Lurie writes on the need for science — basic virology; surveillance; mitigation measures; vaccine development, manufacture, and distribution; operations and logistics; or communication — in planning for pandemics or other emerging infectious diseases.

Dr. Sekar Kathiresan writes about Lp(a) lipoprotein, an unusual molecule that varies widely among human populations (e.g., there is a marked increase in persons of African and South Asian ancestry), and more than 90% of this variability is determined by inherited DNA sequence variation.

These articles are from the issue dated December 24, 2009.

Two SNPs in the LPA locus were strongly associated with both the level of Lp(a) lipoprotein and the risk of coronary disease. These findings support a causal role of an increased Lp(a) lipoprotein level in the riskof coronary disease.

In another article, a study with 30 years of follow-up indicates that early-repolarization patterns in the inferior and lateral leads are associated with an increased risk of death from cardiac causes and from arrhythmia.

This Editorial is from the issue dated December 24, 2009. Jonathan Gruber argues that the primary criticisms of the health care reform bills are largely unwarranted.

This article is from the issue dated December 24, 2009. Images in Clinical Medicine features a 67-year-old woman with a history of breast cancer who underwent routine follow-up chest radiography. Another feature looks at coughing and masks to limit the transmission of infectious agents.

This article is from the issue dated December 24, 2009. New recommendations on screening for breast cancer have raised concerns about access to potentially lifesaving care. Dr. Robert Truog believes that for healthcare reform to progress with clarity, transparency, and honesty, we must discuss how, not whether, we should ration healthcare.

This Case Record of the Massachusetts General Hospital is from the issue dated December 24, 2009. A 29-year-old man presented with fever and respiratory distress. He had fever, a nonproductive cough, and myalgias. On admission to this hospital, he was hypoxemic. Respiratory failure, renal failure, and hypotension developed.

This article is from the issue dated December 24, 2009. A 56-year-old obese man who received a diagnosis of Barrett’s esophagus presents for a follow-up visit. Endoscopic and histopathological examinations show a 4-cm segment of Barrett’s esophagus without dysplasia. How should Barrett’s esophagus be managed?

This article is from the issue dated December 24, 2009. This retrospective analysis used a new, highly sensitive assay for cardiac troponin T. At levels well below the limit of detection of the conventional assay, troponin T concentrations correlated significantly with the subsequent risk of cardiovascular death and heart failure but not with the risk of myocardial infarction.

This article is from the issue dated December 24, 2009. Dr. George Sawaya discusses three major changes that are designed to minimize screening harms while preserving high benefit.

This summary covers the issue of December 17, 2009. Featured are articles on three trials of 2009 H1N1 vaccines, ferric carboxymaltose in patients with heart failure and iron deficiency, limiting industry’s influence on CME, and gene therapy for color blindness; a review article on the molecular basis of colorectal cancer; a case report of a pregnant woman with acute cardiac failure; and Perspective articles on a Republican view of health care reform, on the consequences of “no” to health care reform, and on ensuring equity in health care reform.

This article is from the issue dated December 17, 2009. There is an urgent need for a vaccine to prevent pandemic 2009 influenza A (H1N1) infection. In this report, 95% of adult subjects had a significant immune response (hemagglutination-inhibition titer, >1:40) by day 21 after receiving a single 15-µg >dose of vaccine.

This Case Record is from the issue dated December 17, 2009.

This article is from the issue dated December 17, 2009. Drug and device manufacturers provide more than half the funding for continuing medical education (CME) and indirectly influence its content. The authors describe potential strategies to safeguard CME from bias and to improve its value to clinicians.

This article is from the issue dated December 17, 2009. In this report regarding an MF59-adjuvanted 2009 H1N1 monovalent vaccine, significant immune responses were elicited by the administration of one or two doses of vaccine (with or without the MF59 adjuvant) in most subjects within 2 to 3 weeks. Higher titers were seen in subjects who received the MF59-adjuvanted vaccine.

This article is from the issue dated December 17, 2009. This review gives an account of recent advances in our knowledge of the molecular mechanisms in colorectal cancer. Genetic changes in the germ line, combined with somatic mutations, occur in familial syndromes of colorectal cancer, whereas somatic mutations are the outstanding feature of sporadic colorectal cancer. Genetic changes drive the progression from adenoma to carcinoma and probably influence individual susceptibility and response totreatment.

This article is from the issue dated December 17, 2009. In this 2200-person study conducted in China, the administration of an inactivated vaccine against the 2009 H1N1 virus achieved typical protective immune responses after one dose in subjects between 12 and 60 years of age, whereas two doses were required for younger subjects (3 to 11 years of age).

This article is from the issue dated December 17, 2009. The United States is in the midst of a profound demographic transition. By 2050, non-Hispanic whites will account for less than half the U.S. population and members of racial and ethnic minority groups will be in the majority. This shift is also reflected in the fact that the United States is now home to at least 20 million people who have low proficiency in the English language. Although there are differences among minority groups, all these populations face special challenges. Members of minority groups have higher rates of disease, poorer health, and more limited access to care than their white counterparts.

In patients with heart failure and iron deficiency, intravenous iron therapy improved functional capacity and the quality of life. The benefit was similar in patients with anemia and those without anemia. Iron therapy may have a role in treating heart failure when iron deficiency is also present. This summary includes an editorial on the same topic.

These articles are from the issue dated December 17, 2009. This Images in Clinical Medicine features a 39-year-old man who was found in a snowbank with the ambient temperature -35 degrees centigrade. Also, an otherwise healthy 48-year-old woman presents at the emergency department with colicky diarrhea, vomiting, and diarrhea. In addition, this summary covers an editorial on healthcare reform.

This article is from the issue dated December 17, 2009. This review gives an account of recent advances in our knowledge of the molecular mechanisms in colorectal cancer. Genetic changes in the germ line, combined with somatic mutations, occur in familial syndromes of colorectal cancer, whereas somatic mutations are the outstanding feature of sporadic colorectal cancer. Genetic changes drive the progression from adenoma to carcinoma and probably influence individual susceptibility and response to treatment.

This article is from the issue dated December 17, 2009. Recently, a committee of the Institute of Medicine (IOM) analyzed the current trajectory of our health care system. It studied the dynamics driving downward trends in insurance coverage and examined the health consequences of the lack of insurance for individual adults, children, and communities.

This summary covers the issue of December 10, 2009. Featured are articles on allogeneic hematopoietic stem-cell transplantation for sickle cell disease, platelet inhibition with cangrelor in patients undergoing PCI, and dabigatran vs. warfarin for acute venous thromboembolism; a review article on telomere diseases; a case report of a boy with paroxysmal headaches and visual changes; and Perspective articles on two essential elements of delivery-system reform; on the Supreme Court, process patents, and medical innovation; and on the breadth of hopes.

These articles are from the issue dated December 10, 2009. An editorial outlines the most important lessons on the two trials on cangrelor in patients undergoing PCI. Also, a Case Record of the Massachusetts General Hospital, on a boy first seen in the pediatric neurology clinic at 16 years of age because of paroxysmal headaches and visual changes.

This Perspective article is from the issue dated December 10, 2009. On November 9, the U.S. Supreme Court heard oral arguments in Bilski v. Kappos, one of the most closely watched cases in the Court's current term. The central question involves the legitimacy of a patent on a method for hedging risk in commodities trading, but the outcome will have important implications for health care delivery and research. Although patents covering medicines, devices, and research targets such as DNA sequences have becomecommonplace, in recent years there has been a surge in new patents on medical processes.

Cangrelor is an intravenous ADP-receptor blocker that interferes with platelet function. With a primary end point of death, myocardial infarction, or revascularization, cangrelor was not superior to placebo in patients undergoing PCI. However, there were fewer stent thromboses and deaths in the cangrelor group, leading the authors to suggest that cangrelor deserves further study.

This summary includes an editorial on Allogeneic Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease

This article is from the issue dated December 10, 2009. With discussions about U.S. health care reform focused heavily on insurance reforms, relatively little attention has been paid to the delivery-system reforms that will be required to improve the quality and coordination of health care and slow the growth of spending. The "patient-centered medical home" (PCMH) and the "accountable care organization" (ACO) are two widely discussed models for delivery-system reform that take complementary approaches to achieving these goals.

This article is from the issue dated December 10, 2009. This Perspective article discusses hoping as a fundamental human activity. For this physician, these are heard daily: "I hope we can come up with the definitive diagnosis"; "I hope the treatment makes the disease go away"; "I hope we can relieve his pain"; "I hope we can go home today." Indeed, the word is uttered so frequently in clinical medicine that the underlying phenomenon is widely presumed to be well understood, a shared point of reference. Our understanding of hope, however, is not based on much empirical evidence.

The Nobel Prize in Physiology or Medicine 2009 was recently awarded to three scientists for their work on telomeres, which are repetitive DNA structures at the tips of chromosomes, and the enzyme telomerase. Telomeres protect the genome from loss of genetic material. This review recounts the medical implications of telomeres and focuses on a group of diseases in which the loss of telomeres appears to be causal.

This summary covers the issue of December 3, 2009. Featured are articles on a vaccine regimen to prevent HIV-1 infection in Thailand, management of lung nodules detected by volume CT scanning, abacavir–lamivudine versus tenofovir–emtricitabine for initial HIV-1 therapy, continuous-flow left ventricular assist for advanced heart failure, forecasting the effects of obesity and smoking on U.S. life expectancy, and a look at the low-carbohydrate diet; a review article on mitral-valve repair for mitral-valve prolapse; a Clinical Problem-Solving article describing a crisis in late pregnancy; and Perspective articles on America’s safety net and health care reform and on the emergency use authorization of peramivir for treatment of 2009 H1N1 influenza.

This article summary is from the issue dated December 3, 2009. A vaccine regimen against HIV showed some efficacy against HIV acquisition but did not have an effect on the subsequent viral load or CD4+ count in those who became infected.

This article summary is from the issue dated December 3, 2009. With the use of volumetric methods, the authors found that the chances of finding lung cancer by CT scanning 1 and 2 years after a negative baseline test were 1 in 1000 and 3 in 1000, respectively

This article summary is from the issue dated December 3, 2009. This comparative-effectiveness trial assessed clinical outcomes in patients with advanced heart failure who had a continuous-flow left ventricular assist device as compared with a pulsatile-flow device. The continuous-flow device resulted in better clinical outcomes.

This article summary is from the issue dated December 3, 2009. A 31-year-old woman in the 37th week of an uncomplicated pregnancy presented to the emergency department with severe bitemporal headache and shortness of breath of gradual onset.

This article summary is from the issue dated December 3, 2009. The authors forecast that the adverse effect of increases in obesity on the nation’s health over the next decade will exceed the benefits of declines in smoking.

This article is from the issue dated December 3, 2009. Mice that were fed a high-fat, high-protein, low-carbohydrate diet were found to have atherosclerosis that was not associated with traditional cardiovascular risk factors.

This article is from the issue dated December 3, 2009. On October 23 the FDA issued an Emergency Use Authorization for peramivir for the treatment of suspected or confirmed cases of 2009 H1N1 influenza. Drs. Debra Birnkrant and Edward Cox discuss the limited data on safety and efficacy and the criteria for emergency use of peramivir.

This article is from the issue dated December 3, 2009. Patients with HIV-1 RNA levels of 100,000 copies per milliliter or more were significantly less likely to have virologic failure if they were assigned to tenofovir DF–emtricitabine than if they were assigned to abacavir–lamivudine.

This article is from the issue dated December 3, 2009. With major reform imminent, what will happen to Medicare, Medicaid, and the Children’s Health Insurance Program — safety-net programs that serve some 100 million Americans? Dr. Irwin Redlener and Roy Grant write that the existing safety net is continuing to deteriorate.

This article is from the issue dated December 3, 2009. A 74-year-old man was admitted to our hospital after presenting with fever, nonproductive cough, and a 2-month history of enlargement of the left breast. Examination showed gynecomastia on the left side with bilateral crepitations of the lung. Computed tomography (CT) of the thorax showed a left-chest-wall collection of fluid with erosion of the ribs and extension into the pleural space, anterior mediastinum, and lung parenchyma.

This article is from the issue dated December 3, 2009. A 55-year-old man presents with a holosystolic murmur of increasing intensity and is given a diagnosis of mitral-valve prolapse with severe mitral regurgitation. Mitral-valve repair is recommended. Mitral-valve repair may result in a better survival rate than mitral-valve replacement, but mitral regurgitation can recur.

This summary covers the issue of November 26, 2009. Featured are articles on niacin or ezetimibe and carotid intima–media thickness; biventricular pacing in patients with bradycardia and normal ejection fraction; a novel antibody associated with autoimmune pancreatitis; and rituximab, B-lymphocyte depletion, and preservation of beta-cell function; a review article on diuretics for hypertension; a case report of a woman with chronic renal failure, leg swelling, and skin changes; and Perspective articles on pain management, drug safety, and the FDA; on getting to the real issues in healthcare reform; and on controlling US healthcare spending.

This article is from the issue dated November 26, 2009. In patients who have, or are at risk for, coronary artery disease, niacin added to statin therapy resulted in regression of the carotid intima–media thickness. In contrast, ezetimibe added to statin therapy paradoxically resulted in progression of the carotid intima–media thickness.

This article is from the issue dated November 26, 2009. In this comparative-effectiveness trial, biventricular pacing prevented the reduction in left ventricular ejection fraction that is seen with right ventricular pacing.

This article is from the issue dated November 26, 2009. Peter Hussey and colleagues identify several policy options that have the potential to reduce health care spending in the United States.

This article is from the issue dated November 26, 2009. A 46-year-old woman with chronic kidney disease and a history of deep venous thrombosis presented with swelling of the leg and skin changes. Thickening and erythema of the skin of both legs developed, leading to difficulty walking, sitting, and bending.

This article is from the issue dated November 26, 2009. Dr. Janet Woodcock describes the FDA’s ongoing effort to strike the right balance between two important goals: providing access to pain medications for those who need them and managing the variety of risks posed by analgesic drugs.

This article is from the issue dated November 26, 2009. This phase 2 study evaluated the role of B-lymphocyte depletion with rituximab in type 1 diabetes mellitus. Rituximab partially preserved beta-cell function over a 1-year period, suggesting that B lymphocytes contribute to the pathogenesis of type 1 diabetes mellitus.

This article is from the issue dated November 26, 2009. Paul Ginsburg writes that the House and Senate proposals are likely to differ in important details.

This article is from the issue dated November 26, 2009. The cause of autoimmune pancreatitis is unknown, and distinguishing autoimmune pancreatitis from pancreatic cancer can be difficult. The authors identified an antibody that they were able to detect in about 95% of patients with autoimmune pancreatitis but in only about 5% of patients with pancreatic cancer.

This review article is from the issue dated November 26, 2009. This review focuses on thiazides, the diuretics most often indicated for long-term therapy for hypertension. Thiazide diuretics reduce blood pressure when administered as monotherapy; thiazides also enhance the efficacy of other antihypertensive agents and can reduce hypertension-related morbidity and mortality.

This editorial is from the issue dated November 26, 2009. This editorial relates to a report on the results of the Pacing to Avoid Cardiac Enlargement (PACE) study, a prospective, double-blind, multicenter trial designed to determine whether biventricular pacing is superior to right ventricular apical pacing for the prevention of adverse changes in left ventricular function.

Dr. Anthony Fiore, CDC liaison to the ACIP Influenza Vaccine Working Group, discusses the clinical spectrum.

This summary covers the issue of November 19, 2009. Featured are articles on a trial of darbepoetin alfa to reduce cardiovascular events, inflammatory bowel disease and interleukin-10 signaling, combined immunodeficiency associated with DOCK8 mutations, a novel protective prion protein variant and kuru exposure, and pancreatic cancer and the hedgehog pathway; a review article on inflammatory bowel disease; a case report of a man with cough, hoarseness, and abnormalities on chest imaging; and Perspective articles on Medicaid and national health care reform, on Massachusetts healthcare reform and the cost of near-universal coverage, and on mandatory vaccination of health care workers.

This article is from the issue dated November 19, 2009. Kuru, a neurodegenerative disease associated with endocannibalism in Papua New Guinea, is the classic example of prion disease. Certain polymorphisms at codon 129 of the prion protein gene (PRNP) are highly associated with susceptibility to the development of kuru. In this report, further investigation involving kuru-exposed survivors in Papua New Guinea shows that certain polymorphisms in PRNP codon 127 lead to genetic resistance to kuru.

This article is from the issue dated November 19, 2009. Defined by a history of both achievement and controversy, Medicaid has once again become central to the US health policy debate, this time figuring as a key to national healthcare reform.

This Perspective article is from the issue dated November 19, 2009. Mandatory vaccination of healthcare workers raises important questions about the limits of a state's power to compel individuals to engage in particular activities in order to protect the public.

This article is from the issue dated November 19, 2009. Genetic analyses showed that mutations affecting the interleukin-10 receptor are associated with early-onset colitis. Further molecular analyses showed that the mutations abrogated interleukin-10 signaling. Treatment of one of the affected children by means of allogeneic hematopoietic stem-cell transplantation was successful.

This article is from the issue dated November 19, 2009. This review gives an account of recent advances in our knowledge of the intestinal immune system and how it becomes perturbed in Crohn's disease and ulcerative colitis. The importance of genetic factors in these diseases has been increasingly recognized, and this article emphasizes their roles.

This article is from the issue dated November 19, 2009. Treatment of a mouse model of aggressive pancreatic cancer with an inhibitor of the hedgehog pathway enhanced tumor sensitivity to gemcitabine and resulted in the stabilization of disease.

This article is from the issue dated November 19, 2009. A 23-year-old man was transferred to this hospital because of cough, hoarseness, fever, and abnormalities on chest imaging. One month before admission, a nonproductive cough developed, followed by hoarseness, dyspnea on exertion, and fever. Imaging studies at another facility showed pulmonary and mediastinal masses and a lesion in the pelvis. Positron-emission tomographicscans obtained at this hospital showed ¹⁸F-fluorodeoxyglucose–avid lesions. A diagnostic procedure was performed.

This article is from the issue dated November 19, 2009. Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. This placebo-controlled trial randomly assigned such patients to receive darbepoetin alfa or placebo. The two composite end points were death or cardiovascular disease and death or end-stage renal disease. Darbepoetin alfa did not reduce either outcome and was associated with an increased risk of stroke.

These cases from Images in Clinical Medicine were published in the issue dated November 19, 2009. 

This summary covers the issue of November 12, 2009. Featured are articles on critical care services and 2009 H1N1 influenza in Australia and New Zealand; hospitalized patients with 2009 H1N1 influenza in the United States, April–June; cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus, revascularization versus medical therapy for renal-artery stenosis, and outcome reporting in industry-sponsored trials of gabapentin for off-label use; a review article on renal-artery stenosis; a case report of a male renal-transplant recipient with renal insufficiency, diabetic ketoacidosis, and mental-status changes; and Perspective articles on market exclusivity for biologics, on the global recommendation for rotavirus vaccination, and on a service for deceased oncology patients.

This article summary is from the issue dated November 12, 2009. A consortium of ICUs in Australia and New Zealand report their experience with admissions associated with infection with the 2009 H1N1 virus.

This summary covers the issue of November 12, 2009. Investigators from the CDC describe the clinical characteristics of the earliest patients to be hospitalized with the virus in the United States.

This article summary is from the issue dated November 12, 2009. CDC investigators found that vaccination with the routine trivalent seasonal influenza vaccine induced little immunity against the current pandemic H1N1 virus and that 34% of subjects born before 1950 had some immunity to this pandemic virus.

This article summary is from the issue dated November 12, 2009. Patients with renovascular disease were randomly assigned either to undergo percutaneous revascularization with medical therapy or to receive medical therapy alone. At 34 months, the rate of decline in renal function did not differ significantly between the two groups.

This article summary is from the issue dated November 12, 2009. Alfred Engelberg and Drs. Aaron Kesselheim and Jerry Avorn discussproposed bills that would guarantee manufacturers 12 years of market exclusivity for a new biologic agent before any biosimilar product couldbe approved.

This article summary is from the issue dated November 12, 2009. A 73-year-old former smoker with a history of hypertension presents with shortness of breath. Imaging shows a diseased aorta and a high-grade ostial lesion of the left renal artery. How should he be further evaluated and treated?

This article summary is from the issue dated November 12, 2009. This article compares outcomes specified in research protocols with those described in published reports for trials of off-label use of gabapentin that were sponsored by the manufacturer. The article details discrepancies between the published record and the research plans.

This case record is from the issue dated November 12, 2009. A 60-year-old man with diabetes mellitus and a history of renal transplantation was admitted to the hospital because of mental-status changes, diarrhea, renal insufficiency, diabetic ketoacidosis, and hypotension. On the fourth hospital day, respiratory distress developed that required mechanical ventilation.

This article summary is from the issue dated November 12, 2009. Drs. Margaret Danchin and Julie Bines write that the global recommendation for rotavirus vaccination marks a major step toward reducing the contribution of rotavirus to child mortality. However, 86% of deaths due to rotavirus occur in Africa and Asia, where the broadening of immunization efforts has been hindered.

This perspective article summary is from the issue dated November 12, 2009. Dr. Ranjana Srivastava accepted an invitation to speak at a semiannual ecumenical service for deceased oncology patients. In this essay, she describes this deeply humanizing experience.

This summary is from the issue dated November 12, 2009. The summary includes an editorial by Richard Wenzel and this issue's Images in Clinical Medicine.

This summary covers the issue of November 5, 2009. Featured are articles on on-pump versus off-pump CABG, vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia, a peptide-based erythropoietin-receptor agonist for pure red-cell aplasia, testosterone and spermatogenesis, and figuring out ferroportin; review articles on phosphodiesterase type 5 inhibitors for pulmonary arterial hypertension and on myelodysplastic syndromes; a Clinical Problem-Solving article describing a bloody mystery; and Perspective articles on doctors, patients, and health care reform, on litigation amidst reform and the Boston Medical Center case, on payment reform for safety-net institutions, and on novel H1N1 influenza and respiratory protection for health care workers.

This article summary is from the issue dated November 5, 2009. This comparative-effectiveness trial showed that clinical outcomes at 1 year were better with on-pump than with off-pump coronary-artery bypass grafting (CABG), and there was also better graft patency.

This article summary is from the issue dated November 5, 2009. In women with grade 3 vulvar intraepithelial neoplasia associated with human papillomavirus type 16, vaccination against HPV-16 infection with a peptide vaccine was related to a clinical response in 79% of patients at 1 year.

This article summary is from the issue dated November 5, 2009,Patients with pure red-cell aplasia were treated with a peptide-based erythropoietin-receptor agonist that simulates the action of erythropoietin. Of the 14 subjects, 13 achieved a hemoglobin concentration above 11 g per deciliter and over the 28-month course of the study lost the need for regular transfusions.

This article summary is from the issue dated November 5, 2009. When evaluating a patient with anemia in whom inflammation is present, the physician typically observes the mean corpuscular volume and then requests biochemical analyses to determine the serum iron and ferritin levels, total iron-binding capacity, and transferrin saturation (calculated as serum iron level divided by the total iron-binding capacity, expressed as a percentage). If the transferrin saturation is less than 10% and the ferritin level is less than 30 ng per milliliter, iron deficiency is diagnosed as the cause of the anemia. If the transferrin saturation is low (15%) and the ferritin level is high (>200 ng per milliliter), inflammatory block is generally diagnosed.

The reason why the mean corpuscular volume is often normal (in 70% of cases) and anemia relatively mild in patients with inflammation is a clinical enigma, because iron delivery to the marrow is limited — as indicated by the low transferrin saturation. In fact, iron delivery to the marrow should be even less when inflammation is present than when there is iron deficiency, since the total iron-binding capacity (an indirect measure of the transferrin level) is low in inflammatory states. A recent study by Zhang et al. appears to solve this mystery as well as addressing an enigma regarding hepcidin and iron absorption in the gastrointestinal tract.

This article summary is from the issue dated November 5, 2009. Drs. C. Jason Wang, Kathleen Conroy, and Barry Zuckerman argue that safety-net institutions should be reimbursed more per patient under any pay-for-quality scheme that is implemented.

This summary covers the issue of October 29, 2009. Featured are articles on the association between susceptibility to fungal infections and a mutation inCARD9, three-year efficacy of complex insulin regimens in type 2 diabetes, antibiotic prophylaxis and recurrent urinary tract infection in children, and human dectin-1 deficiency and mucocutaneous fungal infections; review articles on postexposure prophylaxis for HIV infection and on norovirus gastroenteritis; a case report of a man with sore throat, fever, and rash; and Perspective articles on FDA drug information that never reaches clinicians, on four health care reforms for 2009, and on implementing evidence-based health policy in Washington State.

This article summary is from the issue dated October 29, 2009. Homozygous mutations in the CARD9 gene, with a premature termination codon, are associated with chronic mucocutaneous candidiasis in an Iranian family. Dysfunction of CARD9 impairs the innate signaling of dectin-1, an antifungal pattern-recognition receptor.

This article summary, from the issue dated October 15, 2009, features a 3-year multicenter trial, in which patients with suboptimal glycated hemoglobin levels while receiving metformin and sulfonylurea therapy were randomly assigned to add biphasic, prandial, or basal insulin. During the first year, sulfonylurea therapy was replaced by additional insulin for unacceptable hyperglycemia or subsequently for a glycated hemoglobin level of more than 6.5%. Basal- or prandial-based insulin regimens more often achieved glycated hemoglobin targets. Fewer hypoglycemic episodes and less weight gain occurred with regimens initiated with basal insulin.

This article summary is from the issue dated October 29, 2009. Noroviruses are now recognized as the leading cause of epidemics of gastroenteritis and an important cause of sporadic gastroenteritis among both children and adults. In the United States, more than 90% of the outbreaks of gastroenteritis for which the cause could not previously be identified can now be attributed to this virus. Understanding the nature of immunity to the norovirus is a key determinant for future improvements in the control and prevention of this viral infection.

This article summary is for the issue dated October 29, 2009. A 20-year-old man was admitted to this hospital because of sore throat, fever, and a diffuse rash for 1 week. Testing for streptococcal pharyngitis and mononucleosis was negative. Amoxicillin and clavulanate were prescribed, and the next day, a red, itchy rash developed on the medial surface of his right arm; the lesions became raised, enlarged, and painful and spread from his arms to his legs, back, hands, feet, and perioral area, without mucosal involvement. Examination disclosed a diffuse eruption of tender violaceous-pink papulovesicles, which progressed to hemorrhagic crusting. A diagnostic procedure was performed.

A 24-year-old man presents to an outpatient clinic, reporting that 36 hours previously he had receptive anal intercourse without the use of a condom with an anonymous male partner. The patient is known to the clinical practice and has had several negative tests for human immunodeficiency virus infection, most recently 6 months previously. How should he be evaluated and treated?

This article summary is from the issue dated October 29, 2009. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy would prevent urinary tract infection in children (under the age of 18 years) who had already had one or more microbiologically proven urinary tract infections. Long-term, low-dose trimethoprim–sulfamethoxazole wasassociated with a modest decrease in the number of urinary tract infections in predisposed children.

This perspective article summary is from the issue dated October 29, 2009. Prospects for the enactment of some reform look good, but comprehensive, sustainable reform of the health care system must wait for another day. Republican support for President Barack Obama's ambitious agenda is fading fast, if it ever existed. An imaginative, truly bipartisan approach that moves the system away from employer-sponsored insurance — the Wyden–Bennett plan — has failed to gain any traction. Within the Democratic majority, sharp disagreements in each house, and between the House and Senate, do not augur well for coherent legislation, even if political compromises can be struck.

This summary covers the issue of October 22, 2009. Featured are articles on intensity of continuous renal-replacement therapy in critically ill patients, strict blood-pressure control and progression of renal failure in children, glucocerebrosidase mutations in Parkinson’s disease, cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma, X-linked thrombophilia with a mutant factor IX, and probing prostate cancer; a review article on atypical hemolytic–uremic syndrome; a case report of a woman with fever, abdominal pain, and hypotension after cesarean section; and Perspective articles on why cooperatives and triggers can’t achieve the goals of a public option, on the group health cooperative, and on disappearing diseases and familial dysautonomia.

This article summary is from the issue dated October 22, 2009. The hemolytic–uremic syndrome, which is characterized by nonimmune hemolytic anemia, thrombocytopenia, and renal impairment, occurs most frequently in young children. Most cases are secondary to infection with Escherichia coli O157:H7 and other Shiga-toxin–producing strains. However, approximately 10% of cases are atypical and not associated with infection. This article reviews current concepts about the pathobiology of atypical hemolytic–uremic syndrome and its diagnosis and management.

This summary is from the issue dated October 22, 2009. In this randomized trial involving children with standard-risk hepatoblastoma, treatment with cisplatin alone caused fewer adverse events and achieved rates of complete resection and survival that were similar to rates achieved with treatment with cisplatin plus doxorubicin. These findings suggest thatdoxorubicin is not needed in treating children with hepatoblastoma who are not at high risk for a poor outcome.

This article is from the issue dated October 22, 2009. A 35-year-old woman was transferred to this hospital because of abdominal pain, fever, and hypotension 3 days after an elective cesarean section. On examination, she appeared acutely ill. The temperature was 39.2°C, the blood pressure 70/52 mm Hg, and the pulse 149 beats per minute. The abdomen was distendedand very tender, with rebound. There was erythema and edemain the region of the surgical incision, extending to the left flank, with no drainage. A diagnostic procedure was performed.

This article is from the issue dated October 22, 2009. Genomic "signatures" of prostate cancer and its metastases suggest that the latter are all derived from a single clone in the prostate gland.

This article is from the issue dated October 22, 2009. Senate Finance Committee chairman Max Baucus (D-MT)'s recently-unveiled draft healthcare bill contains no public plan. Instead, it substitutes the largely untested idea of providing federal loans and start-up funds to encourage the creation of decentralized, member-run healthcare "cooperatives." President Barack Obama — while reiterating his support for a public plan — has said that he could support both these alternatives if they could create accountability and competition for private insurance. Could they?

By giving prospective parents the option of terminating affected pregnancies, screening is doing exactly as was intended, but the disappearance of diseases such as familial dysautonomia should also give us pause. On a practical level, will interest and funding shift away from these conditions, leaving affected adults without advocates or the possibility of scientific breakthroughs? And philosophically, is the disappearance of a disease always an unmitigated good? What does it say about — and to — people currently living with a severe genetic disease when prospective parents would rather abort than bear a child with the same condition?

Also, a 23-year-old man with deep-vein thrombosis was found to have a gain-of-function mutation in his factor IX gene. The plasma level of factor IX was normal, but the coagulant activity of the mutant protein was approximately eight times the normal level. A younger brother with the same mutation also had a mutant factor IX with increased coagulant activity.

This summary covers the issue of October 15, 2009. Featured are articles on the clinical course of advanced dementia, functional status of elderly adults before and after initiation of dialysis, interleukin-2 therapy in patients with HIV infection, and the benefits of taxing sugar-sweetened beverages; review articles on bacterial diarrhea and on cell death; a case report of a man with progressive dyspnea; and Perspective articles on controlling expenditures by improving care for patients needing costly services, on contaminated dietary supplements, and on drug shortages and public health.

This article summary is from the issue dated October 15, 2009. In patients infected with human immunodeficiency virus (HIV), an increase in the CD4+ cell count through control of the HIV virus with antiretroviral therapy has emerged as an important surrogate marker of improved health. In two prospective, randomized studies, the addition of interleukin-2 to antiretroviral therapy to increase the CD4+ cell count was not associated with clinical benefit.

This article summary is from the issue dated October 15, 2009. A 47-year-old man reports a one-week history of diarrhea, with grossly bloody stools for the past five days. He reports no history of travel, contacts with sick persons, or underlying gastrointestinal disease. How should he be evaluated and treated for an infectious cause of his illness?

This article summary is from the issue dated October 15, 2009. In the United States today, 10% of patients account for 70% of total healthcare expenditures. Many patients who require high-cost care are people with multiple chronic conditions, many medications, frequent hospitalizations, and limitations on their ability to perform basic daily functions due to physical, mental, or psychosocial challenges. Some well-researched programs have been shown to reduce costs for these patients with complex healthcare needs, but major payment reform would be needed to spread these programs throughout the United States.

This article summary is from the issue dated October 15, 2009. Consumption of sugar-sweetened beverages has increased in recent decades; evidence suggests that consumption of these beverages contributes to obesity and adverse health outcomes. The authors discuss the potential public health and economic benefits of taxing sugar-sweetened beverages.

This article summary is from the issue dated October 15, 2009. In one of the most dangerous cities in the United States, one portly police sergeant has more to worry about than crime. His doctor had been encouraging him for years to lose weight, and like millions of other Americans, he decided to try a weight-loss supplement to help him shed his extra pounds. But instead of losing weight, he lost his job. According to the label, his diet pills, which were imported from Brazil and sold in the United States, contained vitamin E, centella, senna, and cascara, among other "natural" ingredients. Not included on the label was the amphetamine detected in his urine drug screen. The now-unemployed sergeant is not alone. Such contaminated supplements represent an emerging risk to public health.

This article summary is from the issue dated October 15, 2009. A 27-year-old man was seen at this hospital because of progressive dyspnea and decreased exercise tolerance during the past two years. Imaging studies showed diffuse pulmonary fibrosis. The patient had lighter skin than many in his family, although he reported that several family members had light skin and respiratory problems. He had a history of easy bruising. On examination, his skin was pale, and there was clubbing of the fingers and toes, normal breath sounds, pigmented irises, and horizontal nystagmus. A diagnostic procedure was performed.

This article summary is from the issue dated October 15, 2009. Because the public discussion of drugs is dominated by considerations of their safety, effectiveness, and cost, it is easy to forget that medications have to be manufactured from raw materials before they can be prescribed. The continuing shortages of two medications for enzyme-deficiency disorders and of technetium-99m, the radioactive isotope most commonly used in cardiac studies, bone scans, and other diagnostic procedures in nuclear medicine, provide a salient reminder that adequate drug supplies cannot be taken for granted.

This article summary is from the issue dated October 15, 2009. This review is a primer on the three main mechanisms of cell death: apoptosis, autophagy-associated cell death, and necrosis. The authors discuss the clinical implications of each of these types of cell death and indicate where advances in our understanding have inspired new forms of therapy.

This article is from the issue dated October 15, 2009. Whether functional status before dialysis therapy is maintained after its initiation in elderly patients with end-stage renal disease is unclear. This study assessed functional status in all nursing home residents in the United States who began to undergo dialysis between June 1998 and October 2000. The initiation of dialysis in such residents was associated with a substantial and sustained decline in functional status.

This summary covers the issue of October 8, 2009. Featured are articles on defibrillator implantation early after myocardial infarction, microRNA expression, survival, and response to interferon in liver cancer, doxycycline for Mansonella perstans infection, osteoporosis associated with neutralizing autoantibodies against osteoprotegerin, accuracy of conflict-of-interest statements, and gray-matter injury in multiple sclerosis; a review article on DNA damage, aging, and cancer; a case report of a man with abdominal distention and shock; and Perspective articles on the cost of healthcare.

This summary covers the issue of September 10, 2009. Featured are articles on ticagrelor versus clopidogrel in patients with acute coronary syndromes, recurring mutations in acute myeloid leukemia, asymptomatic reactivation of JC virus in patients treated with natalizumab, treatment of progressive multifocal leukoencephalopathy associated with natalizumab, PML after natalizumab monotherapy, and understanding abdominal aortic aneurysm; a review article on parenteral nutrition in the critically ill patient; a case report of a man with fatigue, cough, and peripheral-blood monocytosis; and Perspective articles on the Prometheus Payment model, on proposals for payment reform in Massachusetts, and on the reemergence of PML in natalizumab-treated patients.

This article summary, from the issue of September 10, 2009, features ticagrelor versus clopidogrel in patients with acute coronary syndromes. In a multicenter, randomized trial, ticagrelor - a reversible inhibitor of the adenosine diphosphate receptor P2Y12 - was compared with clopidogrel in patients who had an acute coronary syndrome with or without ST-segment elevation. At 12 months, the primary end point of death from vascular causes, myocardial infarction, or stroke occurred less often with ticagrelor. Ticagrelor was not associated with an increase in the risk of major bleeding.