Title: NEJM This Week: Supplement to the New England Journal of Medicine, Vol. 361, No. 18.

" Welcome to The New England Journal of Medicine audio summary for the week of October 20 ninth 2009. I'm doctor Michael beer. This week's issue features articles on the association between susceptibility to fungal infections and a mutation in card nine. Human decked in one deficiency and -- cutaneous fungal infections. Three years efficacy of complex insulin regiments in type two diabetes. And antibiotic prophylaxis and recurrent urinary tract infection in children. Review articles on post exposure prophylaxis for HIV infection and on -- virus Castro and dryness. A case report of a man with sore throat fever and rash. And perspective articles on FDA drug information that never reach his clinicians. For health care reforms for 2009. And implementing evidence based health policy in Washington State. A home was I discard nine mutation in a family with susceptibility to fungal infections. By -- Oliver clunker from the royal free hospital London. These authors undertook genetic studies of large and sanguine as Iranian family. With multiple cases of chronic -- Cokie Kenya's Camden diocese. To determine whether -- mutated gene was associated with a form of non syndrome make candid diocese. The authors found linkage to a genomic interval on chromosome nine Q including card nine. All four patients had a home was like his point mutation in card nine. Resulting in a premature termination code on Q2 95 X. Healthy family members had wild type expression of the card nine protein. The four patients lacked wild type expression. Which was associated with lower numbers of TH seventeen cells helper T cells producing interleukin seventeen. Functional studies showed that the Q2 95 X mutation. Impairs -- signaling from the anti fungal pattern recognition except her decked in one. And ought to -- form of susceptibility. To chronic new Cokie Kenya's candid diocese is associated with home was -- is mutations. In card nine. Human decked in one deficiency and -- cutaneous fungal infections. By Bart fervor -- from -- university nine Aegon the Netherlands. New -- fungal infections are typically found in patients who have no known immune defects. These authors describe a family in which four women who were affected by either recurrent Volvo vaginal -- diocese or article my kosice. Had the early stop code on mutation. Higher to 38 X in the -- group and receptive decked in one. The mutated form of -- in one was poorly expressed. Did not mediate -- the ten binding. And led to deep factor of production outside accountants interleukin seventeen -- the crisis factor and interleukin six. After stimulation with baited with -- or candidate Albert Cannes. In contrast fungal -- a psychosis and fungal killing. We're normal in the patience explaining why decked in one deficiency was not associated with invasive fungal infections. And highlighting the specific role of decked in one in human you coastal anti fungal defense. In an editorial Stephen Holland from the National Institutes of Health Bethesda Maryland. Writes that it remains to be proven whether the key mechanisms in these cases of severe Camden diocese consist of -- detecting wand signalling at the at the Helio level. Or impaired -- site activation of epic feeling and mediated through cited comments such as interleukin seventeen. The long and largely happy co existence of humans and fungi. Have necessitated the existence of ways to detect and control -- keeping them in their place. Apparently these pathways are different for -- expert Joe Louis and new core. Although we do not yet understand the entire conversation between Lucas cites an epic feeling him. With these two reports we have now overheard some of the keywords that will enable us to listen more thoughtfully. Three year efficacy of complex insulin regiments in type two diabetes. By Rory home and from the University of Oxford in the United Kingdom. In this three year multicenter trial. Patients with sub optimal like hated hemoglobin levels while receiving Matt Foreman and salt funnel -- therapy. Were randomly assigned to and by -- it -- Angel or basal insulin. During the first year saw a funnel urea therapy was replaced by additional insulin for unacceptable -- replacing it or subsequently for -- hemoglobin level of more than six point 5%. Median quite heated hemoglobin levels were similar for patients receiving by forensic seven point 1% provincial six point 8%. And basal six point 9% insulin based -- Germans. However fewer patients had a level of six point 5% or less in the by -- group 31 point 9%. Then in the provincial group 44 point 7% or in the basal group 43 point 2%. With 67 point 7% 81 point 6% and 73 point 6% respectively. Requiring a second type of insulin. Patients who added a basal or preferential insulin based regiment to oral therapy. Had better like hated hemoglobin control than patients who edited by basic insulin based Richmond. Fewer high spoke -- episodes and less weight gain occurred in patients adding basal insulin. In an editorial. Michael rode in from behind a tiny university clinics Dusseldorf Germany. Writes that the treatment algorithms for adding insulin to Matt Foreman insult funnel -- seem relatively simple safe and convenient and applications. However this study used only insulin analogue X which were produced by only one company. Whereas regular human insulin is considered the first choice in consensus statement. There is not sufficient evidence to determine the superiority of insulin analog -- with respect to glucose control and points or cost. Furthermore safety issues such as my coach panic and anti -- popped codec effects which you've been observed with insulin analogue in cell culture. Require further exploration. It seems premature to recommend specific insulin arrangements for patients with newly diagnosed disease. Antibiotic prophylaxis and recurrent urinary tract infection in children. By Jonathan Craig from the University of Sydney Australia. Antibiotics are widely administered to children with the intention of preventing urinary tract infection. But adequately powered placebo controlled trials regarding efficacy are lacking. 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 eighteen years. Who had already had one or more micro biologically proven urinary tract infections. During the study urinary tract infection developed in 13% of patients in the group receiving crime at the -- is all antibiotic group. And in 19% in the placebo group hazard ratio in the antibiotic group zero point 61. In the antibiotic group the reduction in the absolute risk of urinary tract infection six percentage points. Appear to be consistent across all subgroups of patients. Long term load -- crime -- prints often without sizzle. Was associated with the decreased number of urinary tract infections in predispose children. Alejandro hoberman from the Children's Hospital of Philadelphia Pennsylvania. Writes in an editorial that given the modest overall effects -- a one size fits all approach may not be appropriate. The need to detect Mexico your rewrote reflux is probably the most important issue facing parents and clinicians. The treatment effect of prophylaxis. Did not differ significantly between children with reflux and those without re -- Ongoing trials in children with a wide range of grades have Jessica -- you read -- reflux. May tell us whether the diagnosis and treatment of century fox provide any incremental benefit. Post exposure prophylaxis for HIV infection. A clinical practice article by Rafael -- events from the David Geffen school of medicine at UCLA Los Angeles. There are more than 50000 new cases of HIV infection in the United States and two point seven million new cases worldwide annually. Vaccines for the prevention of HIV infection have thus far yielded mixed results. And safe and effective microbe decides to block HIV are not yet available. However HIV infection is not an instantaneous consequence of exposure to HIV. So there may be window of opportunity for preventing infection after an exposure. Prophylaxis is recommended after both occupational and non occupational exposure to HIV. Observational data suggest that such interventions are approximately 80% effective in averting subsequent HIV -- conversion. But they are not a guarantee of protection. Prophylaxis should be reserved for exposures that are associated with a credible possibility of HIV transmission. Usually considered to be at least zero point 1% risk of transmission from a source patient who is known to be HIV positive -- source patient who's here. Logic status is unknown but who is at high risk for HIV infection. Mathematical modeling suggests that the optimal regiment balancing side effects efficacy and cost. Would be a dual nuclear side regiment such as the fixed dose combinations Adobe dean Namibian game. Unless the background rate of viral resistance in the source population. Is greater than 15%. In which case the three drug regiment including a Prodi ace inhibitor would be favored. And audio version of this article is available at any JN dot org. No moral virus Castro into writes a review article by Roger glass from the National Institutes of Health Bethesda Maryland. Recent advances in understanding the molecular biology of -- viruses coupled with applications of novel diagnostic techniques. Have radically altered our appreciation of their impact. -- viruses are now recognized as being the leading cause of epidemics of Castro and rightists. And an important cause of sporadic Castro into Wright is in both children and adults. Although nor virus Castro and dryness is generally mild and of short duration. New evidence suggests that the illness can be severe and sometimes fatal. Especially among vulnerable populations young children and the elderly. Andy's a common cause of hospitalization. For Castro and -- news. Routine diagnostic methods are still unavailable to most clinicians. But epidemiological studies have identified both rapid local transmission and the emergence of novel oral virus strains that spread in the global fashion. Similar to the epochal nature of influenza. Controlling outbreaks of -- virus poses major challenges. Outbreaks that begin with a single common exposure to contaminated food or water can rapidly spread by person to person contact. Stopping the outbreak often requires herculean efforts to clean the environment on cruise ships hospital wards -- disaster -- And even then the epidemics have abated only when the susceptible cool has been exhausted. The treatment for -- virus Castro into rightists like that for other diarrhea illnesses. Is oral rehydration with fluids and electoral -- if the patient is alert and able to drink. Or with intravenous fluids it vomiting and dehydration are severe. A twenty year old man with sore throat fever and rash a case record at the Massachusetts General Hospital by Charles Taylor. A twenty year old man was admitted to this hospital because of sore throat fever and to defuse rat for one week. Testing for streptococcus -- and monitor nuclear losses was negative. A Marxist Dylan and clap -- money were prescribed and the next day a red itchy rash developed on the medial surface of his right arm. Which he thought was poison -- The lesions became raised in the large and painful and spread from his arms to his legs back hands feet and Perry oral area. Without -- coastal involvement. Examination disclosed to diffuse eruption of tender violations pink packet will -- circles which progressed to hemorrhagic -- Cultures of the throat crew are kennel bacterium in politico. The key to the differential diagnosis in this case involves careful more for logic analysis of the patients unusual eruption. The lesions evolved -- synchronous sleep from clear -- Do drop the icicles to centrally umbilical -- flat topped two violations pink capitals. -- demons sometimes target toward -- fuels and bully to potentials and non jewels dealing with hemorrhagic crust. The most salient characteristics. Are the eight synchronous time course of the lesions and their polymorphism nature. Although the focus of the differential diagnosis in this case was on the skin lesion. He'd he'd have a somewhat unusual infection of the -- X with a clinical suspicion of a Perry counselor abscess. Lost in transmission. FDA drug information that never reaches clinicians. A perspective article by Lisa Schwartz from the Dartmouth institute for health policy and clinical practice Hanover New Hampshire. The 2009 federal stimulus package included one point one billion dollars to support comparative effectiveness research about medical treatments. No money has been allocated and relatively little would be needed. To disseminate existing but practically inaccessible information about the benefits and harms of prescription drugs. Much critical information that the FDA -- at the time of approval may fail to make its way into the drug label and relevant journal articles. The most direct way that the FDA communicate the prescribing information that clinicians need is through the drug label. Labels the package answers that come with medications are reprinted in the physician's desk reference and excerpted in electronic references. To ensure that labels -- not exaggerate benefits or play down harm's. Congress might have required that the FDA or another disinterested party write them. But he did not. Drug labels are written by drug companies then negotiated and approved by the FDA. FDA review documents record the reasoning behind approval decisions. Unfortunately. Reviewed documents are lengthy inconsistently organized and weekly summarized. But they can be fascinating providing a sense of how reviewers struggled to decide whether benefits exceed harm's. Yet in many cases information gets lost between FDA review and the approved label. Sometimes what gets lost these data on harm's data on efficacy. And the sense of uncertainty. About the net benefit of drugs. For healthcare reforms for 2009. A perspective article by victor Fuchs from Stanford University California. Prospects for the enactment of some reform look good but comprehensive sustainable reform of health care system must wait for another day. Republican support for president Barack Obama's ambitious agenda is fading fast if it ever existed. Within the democratic majority sharp disagreements in each house and between house and senate do not augur well for coherent legislation. Even if political compromises can be struck. Almost everyone agrees that the present US healthcare system is dysfunctional. It is too costly to incomplete and coverage and to prone to avoidable lapses in quality of care. A true remedy would require major changes in the financing and organization of care. Such changes currently have little support from either politicians or the public. But a start must be made. Although comprehensive change is probably beyond reach this year several specific reforms should and could be enacted. The creation of insurance exchanges. The illumination or limitation of the tax exemption of employer sponsored health insurance. The appointment of an expert commission to -- changes to the way Medicare pays providers. And the provision of -- funding for a quasi independent institute for technology assessment. Each of these changes alone has a high probability of doing some good. Taken together they reinforce each other and lay a foundation for further reforms. Implementing evidence based health policy in Washington State. A perspective article by Gary Franklin from the university of Washington school of public health. Seattle. To address the unsustainable increase in overall health care expenditures. A matter made more urgent by the financial challenge of providing health care coverage for all citizens in this state. The Washington state legislature and successive governors have since 2003. Enacted a -- of statutory policies related to the use of evidence based principles in improving the quality of care. Reducing overused and under use of health care services. And determining what benefits should be covered by the State's public payers. These payers Medicaid the workers' compensation program the state government employee benefit plan and the corrections department. Provide two point nine billion dollars in benefits annually to approximately 773000. Washington's citizens. Through direct fee for service plans. The state government's authority to use evidence based methods now extends to all major types of health care products and services drugs devices surgical procedures. Diagnostic tests medical equipment. And advanced imaging procedures. A centerpiece of this effort is the health technology assessment HTA program. The HTA program is an unusual initiative in the United States. A government sponsored program in which formal methods are used to conduct critical appraisals of surgical devices and procedures medical equipment. And diagnostic tests. And to translate the results of those -- valuations. Into coverage recommendations. The images in clinical medicine features a 68 year old man who had hypertension diabetes and atrial fibrillation. And was being treated with -- for an. Who was discovered snoring and on the Rose Bowl at home. A CT image of the head showed -- cerebellum hemorrhage extending into the mid brain and tentacles. Also featured in the images in clinical medicine is a 39 year old woman with a one year history of stage four melanoma. Who presented with progressive shortness of breath fatigue and -- in the legs. Trans thoracic echo cardiogram -- showed a large -- Carty would fusion. -- swinging of the heart and collapse of the right atrium and left atrium in and I asked of me and diastolic collapse of the right ventricle. Which was consistent with parent card real -- not. Swinging of the heart that is due to a large -- party -- fusion. Is responsible for the B two -- shift in the axis amplitude and morphology of the Q are a central. Electrical alternate names on electric party under. In this patient the condition resulted in pseudo Tutu won atrial and ventricular block pattern. Within -- and QRS interval after every other -- despite ventricular contraction and echo cardiogram. A video from this case is available at any -- M dot org. This concludes the summary of the October 20 ninth issue of The New England Journal of Medicine. We are interested in your feedback about our audio summaries -- comments or suggestions may be sent to audio and any change -- dot org. Thank you for listening."