Cancer of the esophagus, the tube that conveys food from the mouth to the stomach, has increased by a whopping 600% over the last thirty years.  Yikes!  Rick and I expound on PodMed this week, that's a lot of cancer, and a cancer with a poor prognosis.  Now a study in this week's JAMA offers hope for people in the presumed early stages of the disease, using a technique called radiofrequency ablation.  Before citing the specifics of the study, I'd like to first describe why I used 'presumed' in the above sentence.  Research that is at least a decade old suggests that at least some of the rapid increase in the incidence of esophageal cancer is due to gastroesophageal reflux disease, abbreviated GERD, eroding the area of the esophagus that connects to the stomach over time.  That's because stomach contents are regurgitated back into the esophagus, where the tissue is susceptible to damage by the very acidic stomach slurry. Repeated injury leads to a stepwise progression through an inflammatory condition known as Barrett's or Barrett esophagus, until frank esophageal cancer develops.  This is thought to be the case for adenocarcinoma of the esophagus.  Yet attempting to reduce the acidity of reflux by H2 blockers or other types of antacids has proven disappointing in reducing progression, and at least one study I'm aware of also casts some doubt on the Barrett's esophagus goes to esophageal cancer link.  Indeed, today's study also reveals that many people resolve low grade dysplasia on their own, so the solid line relationship really can't be drawn.  Okay, but what about this study?

One hundred thirty-six patients with low-grade dysplasia were randomized to either radiofrequency ablation or to usual care with endoscopic surveillance.  Sixty-eight patients comprised each arm of the study with those who had ablation doing so by one of two techniques over a maximum of five treatment sessions. The primary outcome measure was progression from low-grade to high-grade dysplasia or adenocarcinoma of the esophagus over three years of follow-up. The trial was stopped early because of the clear superiority of the ablation in preventing progression, with almost 27% of the control group progressing compared with 1.5% of the ablation group.  Ablation reduced the risk of progression to adenocarcinoma by 7.4%.

Pretty impressive numbers, of course, and at face value appears to be clear evidence that radiofrequency ablation should be considered in folks with low grade dysplasia.  But hold on, Rick and I discuss.  People who entered this study were examined and their diagnosis confirmed by people who were expert in the field, and the authors themselves state that 50-85% of people thought to have low grade dysplasia were downstaged to Barrett's esophagus when an expert pathologist examined the biopsy.  Moreover there are some people who clear such conditions on their own, and it's worth considering helping that along with even more conservative measures such as weight loss, eliminating alcohol, chocolate, spicy foods and other irritants from the diet, avoiding eating within 4 hours or so of bedtime and so on.  In our quick fix culture this technique appears attractive but seems the potential for overuse is rife.

Other topics this week include screening and intervention for alcohol abuse in college students and measuring hemoglobin A1c as a risk factor for cardiovascular disease, also in JAMA, and e-cigarette use in JAMA Internal Medicine.  Until next week, y'all live well.

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Statins may now have yet another indication, Rick and I reveal on PodMed this week: help in halting brain atrophy in folks unfortunate enough to have progressed to secondary progressive multiple sclerosis, as reported in the Lancet.  And the number of people who do progress is quite large, since multiple sclerosis, or MS, afflicts literally millions of people worldwide.  While the exact prevalence is not known, what is known is that the condition usually develops when people are 20 to 50 years of age, with about twice as many more women than men affected.  After an initial presentation of what is called 'relapsing remitting' disease, where periods of acute inflammatory activity are followed by periods of relative stability, more than half of people with MS will eventually progress to the relentless form of the disease, with concomitant loss of function and a reduced life expectancy of 5 to 10 years.

The hallmark characteristics of MS are plaques, areas where myelin is destroyed in largely white matter areas of the brain and spinal cord, inflammation, and brain atrophy.  Enter statins, specifically simvastatin. In this study 140 subjects with secondary, progressive MS were randomized to high-dose simvastatin (80 mg) or placebo for 24 months. MRI scans of each subject's brain were obtained at baseline, 12 months and 25 months. Brain volume and number of lesions were assessed.  An additional outcome measure included clinical assessment of function and impact of the disease. Cholesterol was also measured.

Impressively, the study reported a 43% reduction in the annualized rate of brain atrophy among those folks who took simvastatin compared to placebo. Predictably, their cholesterol was also reduced.  The drug was well-tolerated and side effects were minimal.  While the brain atrophy score was positively impacted, no other measures demonstrated a benefit, including the appearance of lesions, or clinical or immunological assessments.  The authors conclude that the results are persuasive enough to more forward to a phase 3 trial, and we agree.  We also agree that based on the results of this study, it's likely that many physicians who treat folks with secondary progressive MS will begin prescribing simvastatin off-label, invoking what I like to call the 'chicken soup hypothesis,' that is, it can't hurt.  Said with a heavy New York inflection, naturally.

Clearly, another direction that occurs to us is the utilization of statins earlier in the course of the disease as a potential prophylactic measure.  Rick and I part company here as he cites the fact that effective immunomodulatory agents exist for the initial stages of MS, but I am intrigued by the evident anti-inflammatory effect of statins as discerned in a number of other conditions and situations and wonder if they might not be more helpful if used in this capacity. No doubt future studies will address this question.

Other topics this week include neuraminidase inhibitors and flu mortality in Lancet Respiratory Medicine, genetic profiles and impact of fatty food consumption in the BMJ, and H.influenzae risk in pregnancy in JAMA.  Until next week, y'all live well.

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We're always astonished, Rick and I opine on PodMed this week, when sacred cows are slaughtered in medicine, when some precept we've held dear is subjected to rigorous study and discredited.  Such is the case in this week's New England Journal of Medicine, where surgical checklists, those darlings of the patient safety world, had no impact on mortality or surgical complications.  Sacre bleu!  How can it be so?  Let's take a look at the evidence.

Our friends to the north, residents of Ontario, Canada, provided researchers with a 'natural experiment,' a plethora of data from acute care hospitals gathered before and after mandatory implementation of surgical safety checklists. The Ministry of Health and Long Term Care mandated use of surgical safety checklists beginning in July 2010, and hospitals could employ a list of their own devising, the WHO checklist (previously validated in a number of observational studies) or the Canadian Patient Safety Institute checklist. Each hospital is required to report compliance with surgical safety checklists to a publicly reported database, in which the hospital is individually identified.

Three month intervals were studied for all 133 surgical hospitals in Ontario, one concluding three months before checklist implementation, and one commencing three months after such a list was employed.  All surgical procedures performed during each period of study were included in the analysis. Outcome measures included operative mortality, defined as mortality occurring during hospitalization or within 30 days of the procedure, complications occurring within 30 days of surgery, length of hospital stay, rate of readmission within 30 days of discharge, and emergency department visits within 30 days of discharge.

Comorbidities, the patient's socioeconomic status, sex, age and several other factors were also considered. A total of 101 hospitals were deemed eligible for analysis, revealing an adjusted risk of death of 0.71% before checklist implementation to 0.65% afterward. Other outcome measures were similarly unaffected by utilization of a surgical safety checklist, with such a paucity of impact persisting with multiple means of analysis and utilization of different factors.  Well.  Seems a pretty supportable conclusion.  What are possible explanations?

Compliance could be an issue, the authors indicate, citing previous studies looking at actual rates of compliance and outcomes and showing a linear relationship between the two.  Training prior to implementation has also been shown to help, as does team training.  The authors also invoke the Hawthorne effect, where people who know their work is being scrutinized perform better than under normal conditions.  They also speculate that previous research demonstrating the very significant impact of checklists may have relied upon extensive checklists covering virtually the entire period prior to admission to discharge, or when checklists are implemented along with extensive training of care teams.  Finally, I would cite our colleague Peter Pronovost, a patient safety guru, who told me that once one source of potential errors is minimized or eliminated, it opens the door for other types of errors, an assertion borne out in research in many areas of safety.  For now, Rick and I agree, it seems very unlikely that such lists will be abandoned and perhaps this research will suggest a fruitful area for further endeavor.

Other topics this week include a new blood test for Alzheimer's disease in Nature Medicine, questions about whole genome sequencing in JAMA, and the problem of discontinued randomized clinical trials in the same journal.  Until next week, y'all live well.

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Since HIV became the worldwide scourge it is today, a very few people have somehow become infected, yet avoided disease progression and in some cases, cleared the infection.  Such an observation has also been made in at least one HIV-infected person who received a bone marrow transplant and has subsequently remained virus-free for four years.  As Rick and I discuss on PodMed this week, one common denominator among some of these folks is an aberrant receptor needed by HIV to gain entry to T cells, the class of lymphocytes preferentially infected by the virus.  As reported in the New England Journal of Medicine, this receptor, CCR5, has been genetically modified in the laboratory in T cells, the cells subsequently infused back into the person from whom they originated, and have been able to survive in spite of existing HIV infection.  WOW!

This study enrolled 12 patients who were HIV positive and taking antiretroviral therapy. Each of them received an infusion of autologous CD4 enriched T cells that had been modified with the use of a technology known as 'zinc finger nucleases,' or ZFNs. These amazing reagents can be used to generate specific double-strand cuts in DNA.  For this purpose they were used to bind to a site within the human chemokine receptor 5 gene (CCR5)  and modify it so that HIV was unable to dock to the receptor. Previous research had shown that lymphocytes modified in this way were still capable of responding to stimulation and otherwise functioned normally. Only one subject experienced an adverse reaction which researchers speculate was a transfusion reaction.

Over time these modified lymphocytes remained alive, HIV DNA decreased in most patients, and in one patient HIV RNA became undetectable.  Pretty cool, no?  The authors note that future steps need to include modification of both alleles for this receptor, after discovering that the patient whose HIV was rendered silent already possessed one copy of the CCR5 gene that was modified. They further speculate that autologous stem cells could be modified at both alleles and reinfused into patients, or any number of other strategies. What seems clear is that this study brings to fruition a long term goal of genetic modification that could expand well beyond HIV management.  Kudos!

Other topics this week include two provocative studies in JAMA on strategies to improve the life of children: the impact of casino opening on obesity in Native American children and the mental health impact in children of moving to more affluent neighborhoods from poverty stricken areas.  Our final study was another look at hepatitis C incidence in the United States in Annals of Internal Medicine.  Until next week, y'all live well.

 

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Pregnant women have a lot on their minds, I'm sure we'd all agree.  What with environmental exposures, mortality related to flu strains, psychoactive medications and even OTC meds, it's a wonder the process can be undertaken with any degree of composure.  Enter now, as Rick and I discuss on PodMed, a new type of test that is quick, noninvasive, and very reliable for indicating risk that a fetus might have a genetic abnormality known as aneuploidy, or too many copies of specific chromosomes, as published in this week's NEJM.  The test has the potential to reduce anxiety for pregnant women who undergo routine screening that more often than would be desirable indicates a potential problem.  Not only that, but for the nerds among us the technology is way cool and is rapidly making its way through many other areas of clinical medicine.  What's it about?

Turns out that a bit of fetal DNA is shed from the fetal contribution to the placenta into the maternal circulation.  In the common vernacular that's some of the baby's DNA makes it into mom's bloodstream. This is known in the parlance as cell-free DNA or cfDNA.  There it can be detected when blood is withdrawn by a technique known as 'massively parallel sequencing.'  Yikes.  That means the baby's DNA fragments are detected and copied and analyzed to determine if too many copies of chromosomes 18 or 21 are present. These conditions are known as 'Edwards syndrome' and 'Downs syndrome.'  This last is the most common aneuploidy compatible with life, affecting some 1 in 800 live births and becoming increasingly common with increased maternal age.  Edwards syndrome affects 1 in 6000 live births.

This study is an extension of previous work demonstrating that this technique could be used with great sensitivity and specificity in women at high risk for having a fetus with an aneuploidy, such as older age or a previous pregnancy where aneuploidy was detected. In this case a multitude of low risk women were enrolled, and here's what the results report:

The primary series included 1914 women (mean age, 29.6 years) with an eligible sample, a singleton fetus without aneuploidy, results from cfDNA testing, and a risk classification based on standard screening. For trisomies 21 and 18, the false positive rates with cfDNA testing were significantly lower than those with standard screening (0.3% vs. 3.6% for trisomy 21, P<0.001; and 0.2% vs. 0.6% for trisomy 18, P=0.03). The use of cfDNA testing detected all cases of aneuploidy (5 for trisomy 21, 2 for trisomy 18, and 1 for trisomy 13; negative predictive value, 100% [95% confidence interval, 99.8 to 100]). The positive predictive values for cfDNA testing versus standard screening were 45.5% versus 4.2% for trisomy 21 and 40.0% versus 8.3% for trisomy 18.  This is impressive, we must admit, and calls for adoption of this screening for all pregnant women who choose to be screened.

Other topics this week include an enterovirus vaccine developed in China and causes of fever in African children in NEJM, and another analysis of vitamin E and selenium supplements and prostate cancer in the Journal of the National Cancer Institute.  Until next week, y'all live well.

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If you're a parent of a child who is having or has had recurrent ear infections, and I can answer yes on both counts, you have no doubt heard of tubes that can be placed in your child's ears to prevent infections so those tedious bottles of suspiciously flavored antibiotic solutions can presumably be jettisoned.  As Rick and I reveal on PodMed this week, recurrent ear infections in children are a BIG problem, providing the number one condition requiring medical treatment in children under the age of five years in the United States.  So what happens when you go ahead with the devices, known as tympanostomy tubes as well as a number of other names, and your child still gets ear infections????  That's the subject of a study in the New England Journal of Medicine this week, and it provides us with some good news regarding management.

Two hundred thirty children ranging in age from 1 to 10 years, all of whom had tympanostomy tubes placed but still developed ear infections, known in the parlance as otorrhea, were enrolled in this trial.  One-third were assigned to observation only, one-third to oral amoxicillin–clavulanate suspension, and the final third to a topical solution of hydrocortisone–bacitracin–colistin eardrops.  Regimens included  hydrocortisone–bacitracin–colistin eardrops, administered as five drops, three times daily, in the discharging ear or ears for 7 days, oral amoxicillin–clavulanate suspension (30 mg of amoxicillin and 7.5 mg of clavulanate per kilogram of body weight per day, divided into three daily doses administered orally for 7 days), or observation for 2 weeks.

Parents were asked to keep a diary of medication adherence, complications or adverse events for two weeks, and any ear-related symptoms for six months.  The study physician visited the child at home (study conducted in the Netherlands)  at 2 weeks and 6 months, examined the child's ears and collected the parents' diaries and questionnaires.  The study results indicate the clear superiority of the topical treatment to both oral antibiotics and observation in providing the shortest duration of otorrhea (4 days versus 5 days versus 12 days, respectively).  At 2 weeks of follow-up, 5% of children treated with the topical solution, 44% of those who received the oral antibiotics, and 55% of those randomized to observation remained symptomatic. As Rick and I opine on PodMed, the topical treatment avoids systemic side effects of oral antibiotic treatment such as diarrhea, as well as reducing the potential for developing antibiotic-resistant organisms.  Clearly, topical treatment will also reduce parental stress resulting from dealing with a child with a symptomatic ear infection, so sounds like a win-win to us. Could such a strategy be expanded to include additional populations of children with ear infections?  That's outside the scope of this study but seems worth consideration.

Other topics this week include the use a common antidepressant to treat agitation in Alzheimer's disease in JAMA, ablation therapy for atrial fibrillation in the same journal, and how to treat arteriovenous malformations found incidentally.  Until next week, y'all live well.

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Alcoholism is a huge source of disability and death in our world, as everyone knows. Survey data seem to conclude that about 10% of males and about 3% of females engage in heavy alcohol use, with 10.5% of males and 5.1% of females meeting the criteria for alcohol dependance or abuse in the past year.  Now, as Rick and I discuss on PodMed this week, a complicated study in the Lancet combining economic data with population studies supports the idea that raising the base price of alcoholic beverages would favorably affect alcohol consumption in the group that is most negatively impacted by such consumption: low income people.  Let's examine the study.

The authors employed the Sheffield Alcohol Policy Model, version 2.6, a UK-based database utilizing income and socioeconomic subgroup analysis of alcohol purchase and consumption preferences. Price, type, and place of purchase/consumption were included, as was stratification based on moderate, hazardous and harmful consumers of alcoholic beverages. Moderates were defined as those who consumed less than or equal to 21 units of alcoholic drinks per week for men and 14 for women, hazardous consumed 21 to 50 for men and 14 to 35 for women, and harmful consumed more than 50 among the men and more than 35 among women. A unit of alcohol was calculated as 8 gm or 10 ml of pure ethanol, which of course is not how these beverages are sold, so calculations must be made accordingly. These latter three frequency groups were further categorized into three income groups.  The groups were concomitantly analyzed against rates of morbidity and mortality when a baseline price of 0.45 British pounds ($0.75 US) per unit was imposed on all alcohol sales.

Why was this study done at all, since previous analyses have already estimated that price constraints would disproportionately impact the heaviest drinkers?  What is unique about this study is its use of health data to compel the argument, in light of the fact that the lowest socioeconomic groups bear the biggest brunt of the deleterious consequences of alcohol consumption on both economic and health outcomes. So what did it calculate?

All groups in this analysis immediately reduced consumption when a price floor was established. Those who drank moderately were least impacted, with the greatest change seen in the harmful drinker group, in the lowest income bracket.  Yawn.  But here's the compelling data: persons in the lowest income group would accrue almost 82% of the total reduction in premature death and an increase of over 87% of the quality-adjusted life years of the entire analysis.  Wow!  That's a lot of life saved. As I opine to Rick in the podcast, this model seems to me to be a lot like the one for cigarettes, where increasing price points drive down use, especially among those least able to afford it.  While not usually a fan of the adage that the ends justify the means, in this case such a strategy seems quite supportable and legislators should take note and employ same.  Revenues collected could be diverted to treatment programs thus creating even more benefit to society at large.  A win-win.

Other topics this week include the impact of number of doses of the HPV vaccine received on genital warts in JAMA, a possible treatment for restless legs syndrome in NEJM, and the risk of end-stage renal disease in live kidney donors, also in JAMA.  Until next week, y'all live well.

 

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Traffic fatalities for children have declined by almost fifty percent, the newest data just crunched by the CDC and reported in Morbidity and Mortality Weekly Report (MMWR) establishes.  Good news indeed! Rick and I agree on PodMed this week.  It's always so wonderful when a somewhat tedious practice results in such a dramatic reduction in that hard endpoint of death, and especially death in children.  I say somewhat tedious because as anyone who's reading this probably already knows, kids don't much like car seats of any ilk, and are likely to protest in whichever way they can when buckled into them.  Yet the data is irrefutable and provides a compelling argument to enforce existing law and expand it further, as this paper clearly demonstrates that we have a ways to go.  Let's examine the numbers more closely.

The CDC analyzed data regarding traffic fatalities in the 0-12 year old set from 2002 through 2011.  Deaths per age category and restrained versus unrestrained were also broken out, with children younger than one year of age, one to three years of age, 4 to 7 year-olds, and 8-12 year olds comprising the categories.Data from 2009-2010 was also further stratified with regard to ethnicity, with sufficient numbers to permit reporting for non-Hispanic whites, African Americans, and Hispanics.  The age groups were used that correspond to recommended forms of restraint categories, such as infant seat or booster seat.

The good news is that during this time period, deaths in motor vehicle accidents declined by 43% for all age groups.  Per age category, motor vehicle death rates decreased significantly among children aged <1 year by 45%, 1–3 years by 44%, 4–7 years by 43%, and 8–12 years by 41%. However, of the children who died as a result of motor vehicle accidents, 33% were unrestrained.

Ethnicity was also an important factor in this analysis. Black children had a significantly higher proportion of unrestrained child deaths compared with white children for those aged 1–3 years (47% versus 20%), 4–7 years (46% versus 26%), and for all children aged 0–12 years combined (45% versus 26%).  Hispanic children also had a significantly higher proportion of unrestrained child deaths compared with white children for those aged 4–7 years (50% versus 26%), 8–12 years (55% versus 33%), and 0–12 years (46% versus 26%). As Rick opines in the podcast, this clearly points to the need for culturally sensitive education to inform black and Hispanic parents on the need to provide age-appropriate restraints for their children when they are passengers in motor vehicles.

Another issue worth consideration emerged from this analysis. Only two states in the US, Tennessee and Wyoming, have laws that mandate use of booster seats among older children until they reach the age of 8 years, although children aged 8–12 years had the highest proportion of unrestrained child deaths (45%), based on known restraint use.  Clearly this points to the need to enact laws mandating use of age and size-appropriate restraints for everyone riding in or on a motor vehicle.  As I comment to Rick in the podcast, we've had great national success with seat belt use by adults, and the same should be enacted for children of all ages.

Other topics this week include no help for slowing cognitive decline with tight control of risk conditions in people with diabetes in JAMA Internal Medicine, a new type of medication for post-herpetic neuralgia  and a novel flu virus in the Lancet.  Until next week, y'all live well.

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Chances are excellent that you've probably taken an NSAID, a nonsteroidal anti-inflammatory medication, and you're in good company.  Almost everyone has taken one of this class of pain relievers at least once, and if survey data are to be believed, at any one time about a quarter of adults in the United States use these medications once per week or more.  That's a lot of NSIAD use, and it's worth reviewing that this class would include aspirin, ibuprofen, and naproxen, available over the counter (OTC) domestically and in many countries around the world.  How do these drugs compare with another major player in the OTC pain reliever world, acetaminophen or paracetamol?  Their mechanisms of action are different: NSAIDs work by inhibiting both cyclooxygenase-1 and 2, abbreviated COX-1 and COX-2, both enzymes, and thereby down regulating the production of thromboxanes and prostaglandins, which are involved in inflammation and pain.  Acetaminophen inhibits only COX-2, as does the prescription pain reliever celecoxib. As such these latter two may result in less gastrointestinal bleeding.  So what's the issue Rick and I discuss on PodMed this week?  The FDA has issued a report on the cardiovascular risk represented by NSAIDs, and since so many people are taking them, it's worth taking a look at the report.

The most recent data cited in the report is a meta-analysis of  280 placebo-controlled and 474 active-controlled NSAID trials, representing about 200,000 subjects in many comparisons and study designs. Sixty-eight percent of subjects were female, and 79% Caucasian, with a mean age of 61 years. Most people taking the medications had osteoarthritis (63%), with the next most common condition rheumatoid arthritis (20%). Lots of other data regarding comorbidities, concomitant use of gastroprotective medications or more than one NSAID was also examined when available.  The conclusion of the analysis was that use of these drugs did increase the risk of a vascular event by three in a thousand person years of treatment, with one fatal event. Ibuprofen was associated with a two-fold increased risk in major coronary events but not a statistically significant increase in major vascular events. Naproxen was not associated with major vascular events or vascular death, to which I quipped to Rick that I wish I had purchased stock in Naprosen prior to this report's release.

Gastrointestinal bleeds were also assessed and surprise!  were higher in the ibuprofen group.  Here's the take home as far as I'm concerned:  if you said to me as a patient in chronic pain that I had a very small but real increased risk for stroke and heart attack when I took NSAIDs or COX-2 inhibitors, and I juxtaposed that against daily pain relief, I would chose the small risk every time.  Rick responds to that with the current belle of the ball idea, "shared decision making."  He opines that this is one ideal time to educate the patient on both risks and benefits, ideally tailored to their specific situation, and then stand back and let the patient decide.  My own view of shared decision making is less sanguine, but I do agree that fair or not, its time has come and this may be the perfect illustration of when it should be used.

Other topics this week include a look at childhood obesity in the US in NEJM, the implications of the new cholesterol screening guidelines in Annals of Internal Medicine, and evaluating the potential for child abuse in fractures, in Pediatrics.  Until next week, y'all live well.

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When thinking of ways you'd really like to avoid ending up in life, Rick and I agree on PodMed this week that developing Alzheimer's disease is close to the top of the list, in such salubrious company as ALS and locked in syndrome, and we're in abundant company.  Small wonder then, that research on Alzheimer's disease continues at a blistering pace on every aspect of the disease, with two papers representing four studies published in the New England Journal of Medicine this week on the use of antibodies against amyloid and their potential for helping folks with the disease.  Sigh.  That just about says it all with regard to these two drugs, at least in those disease stages in which they were tested.

Solanezumab and bapineuzumab are the names of these humanized mouse antibodies against beta-amyloid, with the former tested for its ability to reduce beta-amyloid in both plasma and cerebrospinal fluid, while the latter was assessed with regard to its ability to reduce beta-amyloid as seen with PET imaging as well as measurement of tau in the cerebrospinal fluid.  Patients enrolled in the former 2 trials were 55 years of age or older, had been diagnosed with mild to moderate Alzheimer's disease (AD) but without evidence of depression.  Subjects were randomized to 400mg of solanezumab received via IV infusion once every 4 weeks for a period of 18 months or placebo, with over 2000 people enrolled in these two studies. In the latter two trials involving bapineuzumab they also enrolled a couple of thousand folks with mild to moderate AD, aged 50 to 88 years.  They received either 0.5 or 1.0 mg per kilogram of the antibody or placebo via IV every 13 weeks for up to six infusions. Unfortunately neither drug had any impact on the cognitive and functional outcome measures used in these studies.  One group in the bapineuzumab study did show a reduction in CSF tau protein.  As I suggested at the outset, sigh.  While there are multiple reasons why antibody-mediated removal of beta-amyloid in people with mild to moderate AD might not work, it is disappointing. And it calls into question the hypothesis that accumulation of beta-amyloid is the key to the pathology of AD at all.  As has been suggested by others much more expert in this field than me, beta-amyloid may be a mere bystander in this arena and may only have utility as a surrogate for some other process that is so far, undefined.  Clearly, however, as the number of people who are projected to develop AD in the next couple of decades burgeons, as we are constantly refining ways to keep them alive longer, and the sheer number of healthcare providers who are needed to take care of these folks is projected to be huge while the supply is too small, we are headed for a train wreck.  For the moment I will cite Constantine Lyketsos, an AD expert here at Johns Hopkins, who says that while waiting for an effective treatment or preventative, make healthy choices with regard to diet and exercise, don't smoke, and stay socially engaged.

Other topics this week include risks of off-hours heart attack in the BMJ, MS and vitamin D levels in JAMA Neurology, and access to firearms, homicide and suicide in Annals of Internal Medicine.  Until next week, y'all live well. And for those who want to get automatic updates on their smartphone or other device of the podcast, here's the new link so  you can update:

https://itunes.apple.com/us/podcast/johns-hopkins-medicine-media/id792911349?mt=2

Happy listening!

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