imagesCAJIMJS6Most adults will have at least one episode of noteworthy back pain in their lifetime, with many experiencing persistent and often disabling symptoms. In fact, back issues are one major reason people miss work and/or seek medical attention.  Enter then the medicalization of this condition, with a fast forward to injections into the space around affected nerves emerging from the spine, so-called 'epidural' injections, to treat pain.  On PodMed this week Rick and I offer kudos to the authors of this study published in NEJM, assessing whether this strategy is actually of any benefit in alleviating pain.  While for those unfortunate folks who got a dose of fungus along with their injection for back pain this study comes too late, we hope it will turn the tide of epidural injections commonly being employed for this purpose.

Investigators randomized 400 people with lumbar spinal stenosis, or narrowing of the canal through which the spinal cord and nerves must pass down the back, and who also had moderate to severe leg pain because of the condition, to one of two treatments: epidural injections of steroid medication plus a local anesthetic called lidocaine, or simply lidocaine alone. Subjects could receive either one or two injections and were subsequently evaluated six weeks after their first (and perhaps only) injection. Both a disability and a pain scale questionnaire were utilized as the primary outcome measures.

People who received the steroid medication, ostensibly to reduce inflammation in the nerve root and the putative cause of the pain, did no better at the six week assessment than those who received the local anesthetic alone.  Wow!  As background it's worth noting that injections for spinal stenosis have increased by about 300% in Medicare and Veteran's Administration populations over the last two decades, with a concomitant increase in costs. So a huge amount of resources have been devoted to the employment of this technique and this study at least suggests we've been wasting our money.

To be fair it must be admitted that there are several causes of back pain other than lumbar spinal stenosis, and these may be amenable to this strategy.  These authors note that about a quarter of all epidural injections for back pain in the Medicare population and 75% of those in the VA population are due to this condition.  Clearly then the technique cannot be soundly panned until additional studies are carried out but Rick and I both feel it should be considered much more judiciously. As we have advocated in the past, the tincture of time is well worth attempting, and in the case of low back pain, so is weight loss and exercise, perhaps taught with a physical therapist's help.

Other topics this week include an assessment of how often physicians talk about sunscreen with their patients in JAMA Dermatology, bone marrow transplantation for sickle cell disease in JAMA, and celiac disease and a genetic assessment in NEJM.  Until next week, y'all live well.

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451096797Anyone out there remember the TV show 'The Bionic Man'? The central premise involves a guy who is severely injured and subsequently largely rebuilt using bionic parts.  What exactly is bionic?  Wikipedia defines the term this way: Bionics (also known as bionical creativity engineering) is the application of biological methods and systems found in nature to the study and design of engineering systems and modern technology.  Rick and I discuss a bionic pancreas on PodMed this week, based on a study presented at the American Diabetes Association meeting and published in NEJM. This study's senior author is a biomedical engineer who designed an artificial pancreas to resemble a human one, using both insulin and glucagon, the two hormones primarily responsible for regulating blood sugar, to manage same.  The early results look promising indeed, if not quite yet ready for prime time (pun intended).

The paper reports the results of two five-day trials, one in adults and one in adolescents, with type 1 diabetes, who were fitted with a bionic pancreas that automatically monitored blood glucose and utilized either insulin or glucagon to achieve a desirable level with an iPhone app interface.  Previous work by the same group established that in an inpatient setting, the device was capable of managing blood glucose effectively for 48 hours.

So what about the outpatient setting, where variability in all sorts of parameters that directly and indirectly affect blood glucose are operational? Assessing the device in this setting was the intention of the current study. All subjects had previous experience with insulin pumps and glucose monitoring. The adults were resident in a hotel geographically close to the hospital, and their activities were limited to an area within three square miles of the hospital for the duration of the study.  They were also accompanied by a staff member. During the study period they could eat whatever they liked, exercise at will, and were allowed to consume 3 alcoholic drinks per day for men and 2 for women.  The adolescents were resident in a camp for people with diabetes.  For the duration of the study they ate the same meals and participated in the same activities as other campers.  Both groups had abundant data collected on blood glucose, episodes of hypoglycemia and other adverse events, and they all acted as their own controls with a five-day usual care period during which all parameters were recorded as well.

Here's what they found: the bionic pancreas was able to decrease the number of episodes of hypoglycemia in the adult population but not in the adolescents.  The authors speculate this may be due to prompt intervention in the camp setting to avoid such an outcome. Both groups saw a lower mean blood glucose level with use of the bionic pancreas compared to usual care. There were a few issues with the iPhone interface but these spontaneously resolved and infusions resumed as appropriate. The authors caution that the device may overestimate blood glucose if acetaminophen is used, and that currently available glucagon must be reconstituted daily, but Rick and I agree that this is a great proof of concept study that clearly should be ramped up. And it's cool!

Other studies this week include thrombolysis for pulmonary embolism in JAMA, exercise for depression in JAMA Internal Medicine, and mammography outcomes in the BMJ.  Until next week, y'all live well.

 

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479517651Parkinson's disease (PD), a consequence of death of neurons in the brain area known as the substantia nigra, is the second most common neurodegenerative disease in the world, after Alzheimer's disease. This movement disorder affects about 7 million people worldwide and 1 million in the US alone currently, with more to come as many more of us age into our 80s and older since PD occurs more often as people age.  Now for the good news:  in what's known as a 'pragmatic' trial undertaken in the UK and reported in the Lancet, as Rick and I discuss on PodMed this week, an old drug known as L-DOPA or levodopa seems the best choice for most when it comes to initial medical management.

Pragmatic trials attempt to assess interventions as they are implemented in the real world rather than the rarified air of a clinical trial. In this case 1620 people newly diagnosed with PD were randomly assigned to either levodopa, another type of drug known as a dopamine agonist, or yet another class called monoamine oxidase type B inhibitors.  Each of these three types of drugs works by a different mechanism in an attempt to overcome loss of the neurotransmitter called dopamine, normally produced by the neurons that die. People entering the trial were diagnosed by movement disorder experts, were either untreated previously or treated for less than six months with levodopa.  Both subjects and clinicians were aware of which drug was selected.

Data from 7 years of follow-up is presented in this study.  One outcome measure was the mobility subscale of a questionnaire known as the PDQ-39. This self-report data is sensitive to items regarded as important to people with PD but that may not be represented on clinical rating scales. Quality-adjusted life-years were determined along with a host of other outcomes such as  changes in the mini-mental state examination, hospitalizations, and mortality. The study determined that for those assigned to the levodopa arm, small but persistent benefits in mobility scores by self-report were seen.  Moreover, with regard to compliance, "179 (28%) of 632 patients allocated dopamine agonists and 104 (23%) of 460 patients allocated MAOBI discontinued allocated treatment because of side-effects compared with 11 (2%) of 528 patients allocated levodopa (p<0·0001)."  As Rick and I opine in the podcast, this may be regarded as good news since levodopa is off-patent, we have an abundant track record regarding its use, and more sensitive titration of the drug clinically may preclude some of the side effects or at least delay them.

The authors have done a cost analysis that is forthcoming, but predict that the economic analysis will also favor use of L-DOPA.  Since we have so many people who will undoubtedly develop PD in the near term, this is of public health benefit as well.  Finally, Rick and I do mention other strategies such as electrode implantation as promising, but agree that for now, knowing which medication is likely to be most beneficial is very helpful for all concerned.

Other topics this week include two studies from NEJM on managing another common condition, obstructive sleep apnea.  We also look at statins and physical activity in older men in JAMA Internal Medicine, and what happens when insulin is added to metformin for the management of type 2 diabetes in JAMA.  Until next week, y'all live well.

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154216694How many children are maltreated, with 'maltreatment' including neglect, sexual, physical or emotional abuse, each year in the United States?  While it's a safe bet no one really knows the absolute number, a very sobering study Rick and I discuss on PodMed this week and published in JAMA Pediatrics attempts to estimate that number, with disconcerting results.  And by the way, almost everyone agrees said results are almost surely an underestimate.  Okay, what about the study?

Researchers crunched data from the National Child Abuse and Neglect Data System (NCANDS) Child File, which included reports on 5 689 900 children filed between 2004 and 2011 of maltreatment confirmed by Child Protective Services. The main outcome measures of the analysis include the cumulative prevalence of confirmed child maltreatment by race/ethnicity, sex, and year.

Here are the numbers, directly from the manuscript: "At 2011 rates, 12.5% (95% CI, 12.5%-12.6%) of US children will experience a confirmed case of maltreatment by 18 years of age. Girls have a higher cumulative prevalence (13.0% [95% CI, 12.9%-13.0%]) than boys (12.0% [12.0%-12.1%]). Black (20.9% [95% CI, 20.8%-21.1%]), Native American (14.5% [14.2%-14.9%]), and Hispanic (13.0% [12.9%-13.1%]) children have higher prevalences than white (10.7% [10.6%-10.8%]) or Asian/Pacific Islander (3.8% [3.7%-3.8%]) children. The risk for maltreatment is highest in the first few years of life; 2.1% (95% CI, 2.1%-2.1%) of children have confirmed maltreatment by 1 year of age, and 5.8% (5.8%-5.9%), by 5 years of age. Estimates from 2011 were consistent with those from 2004 through 2010."

Yikes!  I am especially taken aback by the fact that most maltreatment occurs while children are very young, and often preverbal. Rick and I both agree that the onus is on healthcare providers, who may be some of the few people who will interact with children at this point in their lives, to be on hyperalert to signs of maltreatment. Rick also points out, as do the authors of the study, that child maltreatment really is a health issue: those who have been maltreated as children are at greater risk for obesity, HIV infection, and mortality than those who have not been maltreated.  They're more likely to engage in criminal behavior, experience mental health problems, and are 5 times as likely to attempt suicide as their non-maltreated counterparts. Indeed, the authors provide the estimate that the cost to society of child maltreatment exceeds or equals that of stroke and type 2 diabetes!

Clearly, these rates of child maltreatment are intolerable.  As the authors state, "these data highlight that the burden of confirmed maltreatment is far greater than suggested by single-year national estimates of confirmed child maltreatment and that the risk for maltreatment is particularly high for black children (between 1 in 4 and 1 in 5, my addition)." This study provides us with greater awareness of the problem, now policies and practices must be developed and implemented to address what is obviously a public health issue.

Other topics this week include the utility of colorectal cancer screening in previously unscreened elderly in Annals of Internal Medicine, and two from the BMJ: early stroke thrombolysis benefit, and the statin/diabetes relationship.  Until next week, y'all live well.

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180957061Direct to consumer advertising on the part of pharmaceutical companies has gotten a lot of negative press, and with good reason, several studies have supported. That's because such advertising frequently stimulates people to demand specific medications from their healthcare providers, who often simply write the prescription rather than engage in a prolonged discussion about why or why not it is appropriate.  Now such advertising on the part of cancer treatment centers may also take it on the chin, with a study Rick and I discuss on PodMed this week in Annals of Internal Medicine.  The study examines the content of such advertising and we hope will at least bring awareness to the fore.

Researchers examined cancer center advertising content in the top 44 US television networks and 269 consumer magazines in 2012. During that time there were 409 unique clinical advertisements placed by 102 cancer centers. It's also worth noting that in 2012 more than 1500 cancer programs were accredited by the American College of Surgeons, and this number remains on a strong upward trajectory, along with a predicted increased in the number of cancer cases as the population ages; a 45% increase in cancer incidence is expected by 2030! Okay, so what about the ads?

The majority of both television and print advertisements featured treatments (88%), and were emotional in content (85%). Emotional appeals included evoking hope for survival in 61%, positioning cancer treatment as a fight or battle in 41%, and inducing fear in 30%. About half of the ads featured patient testimonials, usually focused on survival.

In contrast, only about 18% of the ads featured cancer screening, risks of therapy 2%, costs of therapy in 5%, and insurance matters 0%.  Disclaimers about outcomes were seen in only 15% of advertisements, and never described the results a typical patient might expect.  Hmmm.  If the rationale for placing ads includes a desire to provide potential patients with treatment options, this look at advertising practice seems a bit skewed at best.

So, should we either abolish or regulate more closely direct-to-consumer advertising?  Recognizing that the public has a vested interest in an answer to that question, an editorialist in the same issue of Annals reveals data from a survey asking the question of whether medical advertising directly to consumers should be modified or abolished, and the majority of respondents answered no. In point of fact only a small percentage were in favor of any regulation at all.  What then?  Rick and I agree that a more even-handed approach would be welcome, with perhaps development and advertisement of an objective, independent database comparing prices, services, and outcomes regionally and nationally among cancer centers.  Perhaps such a strategy, if utilized by consumers, would help level the playing field with regard to informing consumer choice.

Other topics this week include the possible utility of venlafaxine for hot flashes in menopause in JAMA Internal Medicine, several studies on treatments for pulmonary fibrosis in NEJM, and a new antibody for asthma treatment in the same issue.  Until next week, y'all live well.

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467090685Electronic cigarettes or e-cigarettes appeared to get some great press this week with the release of a study published in the journal Addiction, and one of the line-up Rick and I discuss on PodMed . The study's superficial conclusion is that folks who were attempting to quit smoking and who used e-cigarettes to support their efforts were more successful than either those who used other forms of nicotine replacement or those who tried to go cold turkey.  But hold up, everyone, turns out that a closer look at the methodology of the study as well as the interpretation of the data reveals a lot of holes, and doesn't really answer the question the study purports to ask: do e-cigarettes help people who'd like to stop smoking do so?  Let's see what they did.

Researchers in the UK enrolled almost 6000 adults who had smoked within the previous 12 months and made at least one attempt to cease smoking during that time. Of that number, the majority elected to make the attempt without use of nicotine replacement therapy bought over-the-counter (NRT), where the majority of nicotine replacement products in the UK can be found, while 1922 did utilize OTC NRT, and 464 used e-cigarettes. Surveys were administered to the subjects as part of the ongoing UK Smoking Toolkit Study, which is attempting to gather information about smoking behaviors in England. For this study data from July 2009 through February 2014 was aggregated with the following exclusions: folks who combined methods such as e-cigarettes and NRT, prescription NRT use, or behavioral therapy. The primary outcome measure was self-reported smoking cessation.

Briefly, the study finds "the adjusted odds of non-smoking in users of e-cigarettes were 1.58 (95%CI 1.13 to 2.21) times higher compared with users of NRT bought over-the-counter and 1.55 (95%CI 1.14 to 2.11) times higher compared with those using no aid. In another model that included another measure of dependence (HSI; missing data 3%, n=172), the adjusted odds of non-smoking in users of e-cigarettes were 1.63 (95%CI 1.15 to 2.32) times higher compared with users of NRT bought over-the-counter and 1.43 (95%CI 1.03 to 1.98) times higher compared with those using no aid."  Simply put, those who used e-cigarettes were 1.5 times more likely to quit successfully compared to those using other methods.  Now, what about the holes?

Importantly, Rick points out, there was no assessment of durability of self-reported quitting. In contrast to almost all of the available evidence, this study pans NRT, at least as obtained over-the-counter.  And clearly, we wouldn't be true to our biases if we didn't state that the best and most convincing evidence remains to be gathered: a prospective, blinded, randomized trial of a large number of matched smokers comparing the methods of achieving smoking cessation over a prolonged period of time.  Wonder if e-cigarette manufacturers, so reluctant to have their products regulated as smoking cessation aids, would step up to such a funding opportunity?

Other topics this week include two from JAMA: genetic analysis and lung cancer treatment, and bronchitis and antibiotic treatment, and one from Diabetologia on the risk of cardiovascular disease in women with diabetes.  Until next week, y'all live well.

 

 

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178362592Should you quaff red wine and consume other sources of resveratrol, one of the compounds that's purported to impart health benefits found in this beverage as well as chocolate, berries, grapes and some roots?  Not according to a study Rick and I discuss on PodMed this week, and as reported in JAMA Internal Medicine by our colleague Richard Semba.  Here's what they did: almost 800 residents of the Chianti region of Italy 65 years and older were enrolled in this study, called Invecchiare in Chianti (InCHIANTI) Study (“Aging in the Chianti Region”).  Got to love the Italian! Roughly equal numbers of men and women were enrolled.

Study participants were followed for 9 years, during which time just over 34% of them died. Urinary metabolites of resveratrol were measured at baseline from 24 hour urine samples. Blood tests for inflammatory markers, glucose, and cholesterol and triglycerides were performed. Data on alcohol consumption, smoking status, and physical activity were also collected by self-report. Nutritional supplements were used by less than 1% of the study population.

The dataset was divided into quartiles based on resveratrol metabolites.  Interestingly, the highest quartile also had the greatest number of men, current smokers, and those who both consumed more alcohol and exercised more, and had the least degree of cognitive impairment as assessed with the Mini-Mental State Examination (MMSE).  Those in the lowest quartile experienced more diabetes and coronary artery disease.

Based on the previous findings, it might seem predictable that other factors would also vary according, but as is stated in the study, "There were no significant differences across the quartiles of total urinary resveratrol metabolite concentrations by age, education, BMI, CRP, IL-6, IL-1β, TNF, mean arterial blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, or by prevalence of hypertension, heart failure, peripheral artery disease, stroke, cancer, and chronic kidney disease."  Finally, regarding the hard endpoint of death: "Total urinary resveratrol metabolites concentration was not significantly associated with mortality in models adjusting for age, sex, BMI, serum levels of lipids, chronic diseases, and other variables."  Additional analyses and adjustments were made and the lack of any positive association with a reduced death risk persisted.

This certainly is disappointing for those of us who've bolstered our consumption of red wine with the comforting supposition that it's good for us! Yet as both the author of the study and Rick intone, we should simply drink good wine, and not worry about whether it will prolong life since it clearly helps in enjoying life more.  Additionally, we do know that modest alcohol consumption, a glass for women and a couple of glasses for men each day, does reduce cardiovascular events.  What about supplementation with higher doses of resveratrol?  This study can provide no data on that practice since these were dietary levels presumably achieved with wine consumption, but based on the lack of any hint of a benefit in this study, sure seems like this is one more supplement for the slag heap.

Other topics this week include complications of male circumcision with age in JAMA Pediatrics, football, concussion and change in the volume of the hippocampus in JAMA, and a novel treatment for metastatic cancer in Science.  Until next week, y'all live well.

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Autism spectrum disorders, or ASD, appear to be increasing in prevalence, if statistics reported by the Centers for Disease Control and Prevention are to be believed. In 2014 one in 68 children in the US was diagnosed with ASD, with boys four times as likely as girls to be affected. That's up from one in 88 children in 2012.  Educators, public health officials and most frantically, parents are all trying to discern the antecedents.  Now, as Rick and I report on PodMed this week, a very clever Swedish study reported in JAMA may shed some light on the issue.

Investigators examined data from almost 2 million children born in Sweden between 1982 through 2006. Twin pairs, both identical (monozygotic) and fraternal (dizygotic), full sibling pairs, half-sibling pairs with either the same mother or the same father, and cousin pairs were all identified. A total of 14, 516 children were diagnosed with ASD, of whom 5689 had the most severe form, referred to in this paper as 'autistic disorder.'

This study introduced me to a new acronym for assessing disease risk within a genetic model:  RRR for relative recurrence risk.  Briefly, this statistic purports to pinpoint familial aggregation of disease by calculating the relative risk of a subject with a sibling or cousin with the particular disease or condition as compared to the risk seen in a subject who has no affected sibling or cousin. After adjustments for age, birth year, gender, age of parents and their psychiatric history, RRR was calculated for both ASD and autistic disorder.  Since most of us, (including me!) don't really appreciate RRR as informing our understanding of disease risk, instead of those numbers I cite others the authors calculate: For individuals with a full sibling with ASD, the cumulative probability of an ASD diagnosis at age 20 years was estimated to be 12.9% compared with 1.2% for individuals without. The cumulative probability of an ASD diagnosis at age 20 years was 59.2% for monozygotic twins, 12.9% for dizygotic twins, 8.6% for maternal half siblings, 6.8% for paternal half siblings, and 2.6% for cousins.

There, that sums up nicely, I think, the kind of risk explanation parents might find useful when attempting to understand the risk of having a second affected child when they've already had one. The other number this study provides is an estimate of the impact of genetic factors versus environmental factors in ASD: 50%.  That is, based on this data the authors calculate that 50% of the blame, if you will, rests within the genes, while the remaining 50% can be attributed to environmental influences.

Here's one really interesting statement the authors make:  The male:female ratio was 2.7 for ASD cases and 2.4 for autistic disorder cases. This statement seems to support one of Rick's concerns, that because this study is limited to Swedish children, we may not be able to extrapolate the conclusions to more genetically diverse populations, since the male:female ratio here in the US is reported as 4:1. We agree that the study is important but clearly begs the question of the identification of significant environmental influences.

This week we also look at increasing rates of diabetes in US youth, in JAMA, and reduced mortality when health insurance is mandatory in Annals of Internal Medicine, as well as vaccinating pregnant women for pertussis, also in JAMA. Until next week, y'all live well.

 

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Autopsy, or postmortem examination, is often the stuff of crime thrillers these days, limited in use to circumstances of suspicious death. Popular depictions of the procedure in the media often feature cold, forbidding tile-bound rooms with stainless steel tables and a multitude of refrigerated cadaver bays, more often than not presided over by a white-coated, gloved pathologist who slips out to the loading dock to smoke a surreptitious cigarette even while confronted with abundant evidence of mortality.  Hmmmm.  Small wonder then that most family members decline a postmortem examination for their loved one.  Yet as Rick and I discuss on PodMed this week, as revealed in Annals of Internal Medicine, a new technique that isn't invasive or destructive seems poised to revive the procedure, with likely benefits for all.

Virtual autopsy with multiphase postmortem computed tomographic angiography, known by the much more friendly acronym PMCT angiography is a technique combining CT with injection of blood vessels with contrast medium after death. This study employed the technique in fifty hospitalized patients who died unexpectedly or within 48 hours following an event requiring cardiopulmonary resuscitation. Both PMCT angiography and traditional autopsy were performed in each patient.  Of the 336 diagnoses gleaned from medical records prior to the patient's death, virtual autopsy confirmed 93%, compared with 80% confirmation using medical autopsy. Additionally, 16 new major diagnoses and 238 new minor diagnoses were identified using both techniques, with 32 cases of coronary artery stenosis identified by the CT method. Additional unique findings were also found with virtual autopsy but not with medical autopsy.

Okay, so the PMCT angiography seems to be superior in terms of finding new causes or contributory factors to a patient's death, but what's the point of that?  The authors cite the estimate that about 15% of diagnoses are routinely missed by clinicians, and correctly establishing these diagnoses is likely to result in a more educated clinician at least, and hopefully one poised to utilize additional information that may prolong life for some.  Why have autopsies fallen so far out of favor? Physicians may be reluctant to ask, family members often decline, everyone seems to have greater faith in modern diagnostic techniques, and clinical workflow may preclude a window of opportunity to conduct such an examination.  Who will pay for PMCT angiography? And what happens if data reveals that a clinician missed a diagnosis?  While all of these are considerations, the fact remains that autopsy provides a valuable opportunity to add to the body of information relative to diseases and conditions, and routine employment of the technique could spot trends or upticks in disease incidence earlier than they may be seen otherwise.  The virtual technique also avoids what some family members may view as desecration of their loved one's body.  Clearly, Rick and I are in favor of increased employment of PMCT angiography as a means to provide information to aid the living.

Other topics this week include fibrinolysis for pulmonary embolism in NEJM, chemotherapy and peripheral neuropathy in the Journal of Clinical Oncology, and trying to decrease use of benzodiazepines in the elderly in JAMA.  Until next week, y'all live well.

On an entirely different note, Rick and I would like to extend our thanks to Alejandro Delgado and colleagues at Albert Einstein Medical Center in Philadelphia, for hosting us recently to give Grand Rounds. It was a great pleasure to talk about one of our favorite subjects, PodMed, to such a welcoming and enthusiastic audience.  We're thankful they didn't ask us any questions that stumped us; this group has recently chalked up victory in the ACC Jeopardy competition.  Thanks again!

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Sildenafil, usually marketed under the brand name 'Viagra,' is a very popular drug in the US and around the world for treating erectile dysfunction in men. A recent analysis of the pharmaceutical industry revealed that sildenafil was in the top fifty drugs purchased in the last quarter of 2013.  Rather disturbing then, as Rick and I discuss on PodMed this week, that a JAMA Internal Medicine study reveals a possible association between the use of sildenafil and melanoma.  Yikes!  What's up with that?

The paper cites the fact that almost 80,000 new cases of melanoma will occur this year in the US alone, and that while the pathways underlying disease initiation and progression are complex, the RAS/RAF/MEK/ERK pathway is known to be important in most of them. Moreover, 50% of melanoma tumors have BRAF mutations, leading to elevated kinase activity.  The enzyme PDE5a is a downstream target of BRAF, downregulating it and allowing conditions that favor tumor growth. Lo and behold, sildenafil also targets the same enzyme! Thus the "smoking gun" or biological plausibility we all like to see when examining studies of this nature most definitely exists.

To investigate the association between sildenafil use and melanoma, data from the Health Professionals Follow-Up Study was utilized.  This study began with almost 52,000 US male health professionals enrolled in 1986. Over 90% of them have been faithful through biennial follow-up questionnaires over the interim. This study examined sildenafil use and both melanoma and non-melanoma skin cancers. Data regarding ability to achieve and maintain erection was gathered as well as skin characteristics such as number of moles, natural hair color, number of blistering sunburns, state of residence, and family history of melanoma.

The study identified 142 melanoma, 580 squamous cell , and 3030 basal cell cases during follow-up. Recent sildenafil use at baseline was significantly associated with an increased risk of subsequent melanoma with a multivariate-adjusted hazard ratio of 1.84, or almost twice the risk.  No such association was seen for either squamous or basal cell cancers. Erectile function itself was not associated with an altered risk of melanoma. Men who used sildenafil were likely to be older, weigh more, and have a history of severe or blistering sunburns.

As Rick is quick to point out, this study only provides an association, and therefore clearly needs follow up in the form of a prospective study, but we also agree that since many of the sildenafil prescriptions written nationally, and we suspect internationally, come from primary care physicians, a whole-body skin examination is also in order, with regular repeats while sildenafil is taken, and even after use ceases, as this study found an association with ever-use and melanoma risk as well.

Other topics this week include motion in people with paraplegia in Brain, zinc and colds in JAMA, and shock wave therapy for tendonitis in Annals of Internal Medicine.  Until next week, y'all live well.

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