iStock-478561284Parkinson's disease is a very common neurodegenerative disease, affecting over 50 million people worldwide in 2013, recent data estimate. And who among us hasn't seen the shaking hands and shuffling gait typical of this debilitating condition?  The bad news is the relentless progression of the disorder, with depression and dementia frequently developing. Now, as Rick and I discuss on PodMed this week and published in JAMA Neurology, an assay looking at a misfolded protein called alpha-synuclein may help in diagnosis, progression, and perhaps ultimately treatments or cure.  And the study introduces to us a new technique for amplification of small amounts of protein, which we predict will have great clinical utility in lots of conditions.

The novel technology here is called 'protein misfolding cyclic amplification or PMCA,' and it takes advantage of the fact that misfolded proteins such as alpha-synuclein cause additional aberrant protein to form, thus allowing amplification of the signal to a detectable level. PMCA was utilized to detect alpha-synuclein in the cerebrospinal fluid of 76 people with known Parkinson's disease and 65 others with a different neurological disorder. In short, PMCA was 88.5% sensitive and 96.9% specific in identifying those with Parkinson's and was also correlated with symptom severity. As Rick and I also note, it would be great to have something other than CSF to test to render PMCA more practical, but this proof of concept study is heartening.

Other topics this week are all from NEJM: Revascularization of Left Main Coronary Artery DiseaseCrizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease, and Thromboprophylaxis after Knee Arthroscopy and Lower-Leg Casting. Until next week, y'all live well.

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iStock-489309852People who are frail don't do as well during and after surgery as those who aren't. Duh. Now a study Rick and I discuss on PodMed this week and published in JAMA Surgery attempted to assess frailty preoperatively and develop a plan for afterward, with results that are impressive indeed.

Beginning in October 2007 to July 1, 2014, all patients who came to a single Veteran's Administration medical center for major, elective non-cardiac surgery were assessed preoperatively using a frailty index, and those who were identified as frail comprehensively evaluated by a multidisciplinary team, who created a plan for their care. Here are the results directly from the paper:

Results  From October 1, 2007, to July 1, 2014, a total of 9153 patients underwent surgery (mean [SD] age, 60.3 [13.5] years; female, 653 [7.1%]; and white, 7096 [79.8%]). Overall 30-day mortality decreased from 1.6% (84 of 5275 patients) to 0.7% (26 of 3878 patients, P < .001) after FSI implementation. Improvement was greatest among frail patients (12.2% [24 of 197 patients] to 3.8% [16 of 424 patients], P < .001), although mortality rates also decreased among the robust patients (1.2% [60 of 5078 patients] to 0.3% [10 of 3454 patients], P < .001). The magnitude of improvement among frail patients increased at 180 (23.9% [47 of 197 patients] to 7.7% [30 of 389 patients], P < .001) and 365 days (34.5% [68 of 197 patients] to 11.7% [36 of 309 patients], P < .001). Multivariable models revealed improved survival after FSI implementation, controlling for age, frailty, and predicted mortality (adjusted odds ratio for 180-day survival, 2.87; 95% CI, 1.98-4.16).

Rick and I agree that this is impressive indeed, and I am especially impressed by the statement I bolded above, that even among those who weren't deemed to be at risk such an assessment substantially improved outcomes. And among all comers, the results were durable for 180 days.  Sounds like a clear imperative to implement such a strategy globally.

Other topics this week include Accuracy of a Deep Learning Algorithm for Detection of Diabetic RetinopathySwimming, aerobics, and racquet sports are linked to lowest risk of cardiovascular death from the BMJ, and Pronounced increase in risk of acute ST-segment elevation myocardial infarction in younger smokers, from Heart.  Until next week, y'all live well.

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iStock-486792042Watching and waiting may take place too long in the UK when it comes to abdominal aortic aneurysms (AAA), a study Rick and I discuss on PodMed this week and as published in NEJM reveals, since a number of dire outcomes seem to result when repair is delayed until a certain size aneurysm is reached And as I chortle to Rick, it isn't often our interventional approach to many medical conditions is validated when compared to more conservative strategies, so this study is noteworthy to me in that regard.

Data from almost 30,000 folks who underwent AAA repair in the UK was compared in this study to almost 280,000 records from those with the same condition in the US. This was during the time period from 2005 through 2012. The impact of the higher thresholds for treatment in the UK was examined through the lens of three outcomes: death relative to the aneurysm, hospitalization relative to AAA, and likelihood of repair. The study found that AAA repair was less likely to be undertaken in the UK, that aneurysm-related death was almost four times more likely in the UK, and that hospitalization due to rupture was more than twice as likely across the pond. The average threshold for treatment was 58.3 millimeters domestically versus 63.1mm in the UK. Hmmm.  Seems like operating sooner rather than later is a better strategy, and Rick and I also note that screening, especially for older men who are current or former smokers, is also important.

Other topics this week include Symptoms and Satisfaction of Patients in the PROWL StudiesHip and Pelvic Fracture Risk Associated With Antihypertensive Medications, and a look a mumps in the US currently from MMWR http://www.cdc.gov/mmwr/index.html, along with measles surveillance.  Until next week, y'all live well.

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Neck-PainPain relief is an important part of maintaining quality of life for many, including me, so NSAIDs, non-steroidal anti-inflammatory medicines, are welcome.  But many studies have rumbled that they may be risky for your heart.  Good news then, as Rick and I discuss on PodMed this week and as published online in NEJM, at least three of them appear NOT to confer increased risk for cardiovascular events, at least in comparison to each other and with certain other caveats.  This as also revealed at the recently concluded American Heart Association meeting.

People who took part in this trial had either osteo- or rheumatoid arthritis and were randomized to either celecoxib (Celebrex), ibuprofen or naproxen at various doses daily. Just over 24,000 subjects were treated for about two years and followed for almost three. Almost 70% of participants stopped taking their drug and just over 27% discontinued follow-up. When looking for the three primary outcomes of cardiovascular death, nonfatal heart attack or stroke, no significant difference was found between the three groups, with about 2.5% experiencing such an event. Additional assessments were also made with regard to renal and gastrointestinal problems, with celecoxib emerging as the least risky.

Rick concludes from this study that at the low doses employed here, and for short duration, celecoxib appears to be safe, but we'd both like to see a more pragmatic trial with higher doses and longer treatment periods. Other topics this week include Randomized Trial of Bilateral versus Single Internal-Thoracic-Artery GraftsGenetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease, and A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. Until next week, y'all live well.

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iStock_80130559_SMALLLazy eye, or amblyopia in medical parlance, affects a surprisingly large number of kids: about 3%! We've probably all seen a child who is being treated for the disorder, with one eye patched so the other is forced to behave in a more functional manner.  Patching has been the standard of treatment for quite some time, but outcomes aren't always quite as good as hoped for, even after prolonged periods of treatment. And even when successfully treated, recurrence is common. Enter then a study in JAMA Ophthalmology Rick and I discuss on PodMed this week: use of iPad games to treat lazy eye, with uplifting results.

Researchers identified 28 children with amblyopia, average age 6.7 years, and randomized them to either an eye patch or to use of an iPad loaded with a game that required binocular vision. They needed to play the game for an hour daily for five days each week. As Rick points out in the podcast, this game was very carefully tailored to appeal to children in this age group. After two weeks of gaming, children in the iPad group had improved more than those in the patch group.  At this point all children were offered the iPad and at four weeks, both groups had experienced the same improvement.  Rick and I both agree that such a strategy seems very attractive and seems likely to be successful at scale up.  We agree with the study authors that longer term follow-up as well as relapse treatment are important, and look forward to seeing more (no pun intended).

Other topics this week include Association Between Intensity of Statin Therapy and Mortality in Patients With Atherosclerotic Cardiovascular Disease in JAMA Cardiology, a new cardiovascular risk prediction tool: http://circ.ahajournals.org/content/early/2016/11/03/CIR.0000000000000467, and Pembrolizumab as Initial Treatment in Lung Cancer in NEJM.  Until next week, y'all live well.

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iStock_000016798528_MediumHeart disease remains the number one killer of people worldwide, and if you've done any looking around in public places like airports you've probably noticed devices prominently displayed that say "AED" for automated external defibrillator. These devices are potentially lifesaving for folks who suffer a certain type of heart attack in public, where someone has the presence of mind to utilize one.  Just how often does that happen and what are the outcomes?  That's one of the studies Rick and I discuss on PodMed this week, as published in the New England Journal of Medicine.

The statistics in this article are so impressive: "Of 43,762 patients with bystander-witnessed ventricular-fibrillation arrests of cardiac origin, 4499 (10.3%) received public-access defibrillation."  The study took place in Japan, one of the countries where such data are available, accessing information gathered between 2005 to 2013.  The primary outcome assessed was survival at one month with a favorable neurological outcome, and not surprisingly, showed that almost 39% of those who were defibrillated by a bystander using the device had a favorable outcome compared with just over 18% of those who did not have an AED deployed on their behalf. That's impressive in my opinion, and lends credence to the idea that both use of AEDs as well as bystander initiated CPR could save lives.  Rick points out though that only ventricular fibrillation would benefit here, and that the majority of such events take place in the home, when neither bystander nor AED are most often available.

Other topics this week, all from NEJM, include Effect of Short-Term vs. Long-Term Blood Storage on Mortality after TransfusionFive-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting and Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. Until next week, y'all live well.

 

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iStock_74168357_MEDIUMBreastfeeding is one of those issues around which there's almost no controversy with regard to health benefits for both mother and baby, so, as Rick and I discuss on PodMed this week and published in JAMA, it's a bit disconcerting that only about 22% of infants born in the United States are exclusively breastfed until they're six months of age, per current recommendations, although it is initiated among 80%. This fact emerged as part of the USPSTF review of the literature regarding the benefits and harms of breastfeeding interventions conducted to enable updating of the guidelines, last done in 2008.

Fifty-two studies with over 66,000 participants were included in this analysis, which took a look at both individual and system interventions to promote breastfeeding.  Data indicate that the individual-level interventions, whether by peers or professionals, were much more likely to result in initiation of breastfeeding and longer duration than system wide programs such as the Baby Friendly Hospital Initiative.  Very modest harms were reported in the review: a couple of subjects reporting anxiety, decreased confidence and concerns about confidentiality after a peer visit.

In short, it appears to Rick and me that more individual level interventions should be designed and employed to promote breastfeeding, although the USPSTF stops short of this assertion.  Other topics this week include http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2571615 on state level smoking and cancer, and two from NEJM:Long-Term Oxygen for COPD with Moderate Desaturation and Child–Parent Familial Hypercholesterolemia Screening.  Until next week, y'all live well.

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iStock_000020076031_MediumIt's' a sure bet that any woman with a diagnosis of breast cancer would like to know whether chemotherapy is likely to benefit her before beginning such a regimen. As Rick and I discuss on PodMed this week, and as published in Cancer, that's the aim of the 21-gene recurrence score assay currently employed clinically.  The study specifically examines both how the test was able to inform treatment recommendations on the part of physicians as well as patient experience.The good news is that in employing the test in women in whom it is indicated, the gene assay seems to bring to fruition the promise of precision medicine. As well, it appears to be both racially and ethnically blind, as no difference across these groups were seen.

The study surveyed almost 4000 women treated for breast cancer in 2013-2014, identified from the Los Angeles County and Georgia Surveillance, Epidemiology, and End Results registries. Surveys, recurrence score and tumor data were linked, and showed that the majority of women who received a low recurrence score received a recommendation against chemotherapy, while almost all with a high recurrence score received a recommendation for chemotherapy. Women themselves reported being satisfied both with use of the test as well as treatment decisions. Of particular note, the authors write,"Personalized recommendations appear to reduce potential overtreatment with chemotherapy and nearly eliminated socioeconomic disparities in treatment after we controlled for clinical factors. This is a notable benefit of incorporating the RS into breast cancer treatment algorithms."

Other topics this week include Recurrence and Complications After Elective Incisional Hernia Repair in JAMA, and two from NEJM: Pulmonary Embolism in Patients Hospitalized for Syncope and Romosozumab in Postmenopausal Women with Osteoporosis.  Until next week, y'all live well.

 

 

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iStock_000053775120_MediumAs a hospital increases its number of ICU beds, more and more people are put on mechanical ventilation, even those with advanced dementia. That's the sobering conclusion of a study published in JAMA Internal Medicine that Rick and I discuss on PodMed this week, and one that also demonstrates no improvement in outcomes for these folks.

The study examined data from just over 380,000 Medicare beneficiaries with advanced dementia from 2000 to 2013. This group experienced over 630,000 hospitalizations.  During this time period use of mechanical ventilation among those patients with advanced dementia, about 75% of whom were bedridden prior to admission to the hospital, increased from 39 per 1000 hospitalizations to 78 per 1000 hospitalizations.  The likelihood that such a patient would be placed on mechanical ventilation increased as a hospital acquired more ICU beds, yet no improvement in outcomes was seen.

Yikes. Rick and I both agree that use of mechanical ventilation in many of these folks is questionable at best.  There are several likely scenarios where such a choice might be made but they point to a common problem: lack of accurate, timely communication between the patient, their family and loved ones, and the medical team.  This problem can be successfully overcome with use of a POLST, or in the state of Maryland a MOSLT: physician order for life sustaining treatment, or Maryland order for life sustaining treatment, respectively. This is an actual medical document that is created between the physician and the patient, or if the patient is unable to communicate on their own their healthcare proxy. It specifically delineates care preferences and along with advance directives, improves the odds that such ultimately futile care will not be rendered.

Other topics this week include Trends in Dietary Supplement Use Among US Adults From 1999-2012, an app for detecting atrial fibrillation: http://heart.bmj.com/content/early/2016/08/26/heartjnl-2016-309993.short?g=w_heart_ahead_tab, and calcium intake and coronary artery calcification: http://jaha.ahajournals.org/content/5/10/e003815.full.  Until next week, y'all live well.

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iStock_000062992601_MediumZika virus infection has circumnavigated the globe, with ongoing research efforts identifying more deleterious effects of infection.  This week, as Rick and I discuss on PodMed and as published in the New England Journal of Medicine, evidence has more definitively linked Zika in adults with the neurological syndrome Guillain Barre.  As we discuss in the podcast, since Guillain Barre may result in an ICU stays and the need for ventilation, and may also have long term sequelae, recognition of this association is important.

Investigators identified 68 patients with Guillain Barre syndrome in Colombia, South America.  A total of 66 (97%) had symptoms consistent with Zika infection prior to development of Guillain Barre, and virological studies were completed on 44 of those.  A median of 7 days elapsed between the onset of Zika virus infection symptoms and development of the neurological syndrome.  The researchers take the evidence of Zika virus infection in toto, including positive biological samples as well as antibody levels, along with the temporal relationship between development of Guillain Barre symptoms and Zika infection, and no evidence of Dengue infection or chikungunya, as consistent with a causative role for Zika.

Rick points out that such information is important clinically, since immune globulin may be helpful, and we both agree that this is a story that continues to unfold.  Other topics this week include Hospital Performance and Life Expectancy after MI,  Association Between Therapeutic Hypothermia and Survival After In-Hospital Cardiac Arrest. JAMA. 2016;316(13):1375-1382. doi:10.1001/jama.2016.14380, and Stimulant Medications and Bone Mass in Children and Adolescents With ADHD.  Until next week, y'all live well.

 

 

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