geoffrey modest medical blogs

bmj article found that there was a relationship between greater physical activity and reduced risk of disability in adults with either known DJD or at high risk (see  physical activity dec knee arth bmj 2014  in dropbox, or doi: 10.1136/bmj.g2472). prospective multisite cohort study of 1680 community dwelling adults aged >49yo with known knee DJD (symptoms in at least one knee with osteophyte and pain, aching or stiffness on most days for at least one month in the prior 12 months) or risk factors for developing DJD (knee symptoms in the prior 12 months, overwt, knee injury causing difficulty walking for at least one week, fam hx of total knee replacemetn for DJD, Heberden's nodes and age 70-79). primary outcome of development of disability  ( defined as difficulty in carrying out activities essential to independent living)  at 2 year followup in those free of baseline disability. also followed a cohort of 1814 adults to assess disability progression as a secondary outcome (this

as perhaps a complementary article to the recent mouse one i sent out on soluble fiber, changes in the microbiome, and asthma, this article also just came out finding that increased variety of foods introduced in the first year of life led to decreased asthma, food allergy and food sensitization, as well as several biological markers of allergy (see  allergy and food diversity in kids j allerg clin immunol 2014  in dropbox, or doi.org/10.1016/j.jaci.2013.12.1044). this was a birth cohort study of 856 children from rural Europe with parents reporting monthly food diaries during the first year of life (which should decrease likelihood of reverse causality). they also assessed environmental factors and the development of allergic diseases up til the kids were 6 years old. results:     --51.5% of kids grew up on farms, 53.6% had at least one allergic parent (note: this may affect generalizability of results)     --dose-response effect: each additional food item introduced into the d

an article and editorial in Nature Medicine looked at dietary soluble fiber, changes in the gut flora (microbiome) and allergic airway disease. there have been articles suggesting that increased dietary fiber (esp soluble fiber) is linked to decreased risk of inflammatory diseases, esp in the gut. there are also some data finding associations between the higher incidence of asthma in those eating western diets and lower incidence on mediterranean diets. one potential explanation has been that gut microbes convert dietary fiber into short-chain fatty acids (SCFAs), which decrease inflammatory pathways in macrophages and dendritic cells, promote development of regulator T cells and maintain intestinal epithelial health.   for a detailed overview, see the editorial:  asthma microbiome editorial nature medicine 2014  in the dropbox, or doi :10.1038/nm.3472. in the current study  (see  asthma microbiome nature medicine 2014  in the dropbox, or  doi:10.1038/nm.3444) , researchers show h

one of the "choosing wisely" items of the american geriatric society is to avoid the use of benzodiazepines in people over 65 yo  because of the associated increased risk of falls and hip fractures . of note, b enzos comprise 20-25% of "inappropriate" scripts for elderly, with prevalence of use at 5-32% in community-dwelling elders.  a study was done of direct-to-consumer advertising to see if that could decrease benzo usage in community-dwelling people >65yo on chronic benzos (see  benzo education in elderly jama intmed 2014  in dropbox, or  doi:10.1001/jamainternmed.2014.949). in this study community pharmacies were randomly assigned to either intervention or control, with approx 150 patients  aged 65-95 yo  in each group. patients in the active arm of the trial got an 8-page booklet with a self-assessment component about benzo use, presentation of evidence of benzo harm, drug interactions, peer champion stories to augment self-efficacy, suggestions for altern

The FDA approved an HPV DNA test for women >25 yo today   (see  http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394773.htm  ). the approved test (cobas test, by Roche) tests for 14 high-risk HPV types, including HPV 16 & 18. the FDA, citing a study by Roche, notes:     --women positive for HPV 16 or 18 should go directly to culposcopy (HPV 16 or 18 are responsible for 70% of cervical cancer)     --women positive for the other 12 types should get a regular Pap test to see if need culposcopy     --although initially approved by the FDA in 2011 as a co-test with Pap, this approval now allows HPV testing to be either part of a co-test with Pap, or a primary screening test.     --the Roche study involved 40K women > 25yo, doing culposcopy/cervical biopsy on those with positive Pap or HPV as well as some women negative for both, with 3 year follow-up, leading to the FDA approval so, raises several questions (i have not seen the Roche study, so cannot com

article in jama pediatrics looked at kids with functional GI disease and assessed the incidence of concomitant celiac disease  (see  irritable bowel dz in kids and celiac dz jama peds 2014  in dropbox, or doi:10.1001/jamapediatrics.2013.4984). background is that approx 1% of US population has celiac disease (often asymptomatic). adults with IBS have approx 4-fold increased prevalence of celiac disease. the present study is a 6-year prospective cohort study in Italy, where prior large epidemiologic studies have found celiac disease prevalence to be in the 0.5-1% range. 992 kids (43% male, median age 6.8y) referred by their primary care MD for recurrent abdominal pain, 782 of whom had diagnosis of IBS, functional dyspepsia, functional abdominal pain, or abdominal migraine by Rome III criteria. these kids were then assessed for celiac disease, with  total IgA, IgA tissue transglutaminase antibody, and endomysial antibodies, then duodenal bx if positive.    results for these 992 children:

article just came out in lancet on a very effective and simple HIV regimen using the new integrase-inhibitor dolutegravir  (see   hiv dolutegravir FLAMINGO lancet 2014  in dropbox, or doi.org/10.1016/S0140-6736(14)60084-2). in the FLAMINGO study 484 patients naive to antiretroviral therapy were put on an investigator chosen background therapy of either tenofivir-emtricitabine (67% of the patients) or abacavir-lamivudine (33%), then randomized to either dolutegravir 50mg daily or the protease inhibitor darunavir 800mg plus ritonivir 100mg. primary endpoint was HIV viral load <50 copies/ml at 48 weeks. patients recruited from 64 research centers in eastern and western europe, US, puerto rico. results, after 48 weeks:     --baseline: 71% white, 25% of african origin; 85% men,  CD4 was 395, 25% with viral load > 100K     --90% on dolutegravir and 83% on darunavir/ritonivir achieved <50 copies/ml (statistically significant)     --in those with baseline viral load >100K,

a recent study developed a clinical prediction rule for uncomplicated ureteral stones (see  kidney stone predictive model bmj 2014  or doi: 10.1136/bmj.g2191).  there were 2 components to the study. first was a retrospective observational study to develop the screening tool, a random selection of 1040 adults (derivation cohort) who underwent non-contrast CT for suspected uncomplicated kidney stone from 2005 to 2010. their data was used to derive the top five factors associated with stones analysis and ascribe points reflecting their importance (see STONE score below). the second study was the validation study, 491 patients where the ER physicians felt that the patient presentation was consistent with ureteral stone.     --for the observational component: the five key factors were -- male sex, short duration of pain, non-black race, presence of nausea or vomiting, and microsopic hematuria.     --in the derivation and the validation cohorts (respectively)             --

general population study in Spain to assess benefits of 23-valent pneumococcal vaccine  (see  pneumococcal vaccine efficacy CID 2014  in dropbox, or DOI: 10.1093/cid/ciu002).   PPV-23 was recommended for all people over 60 yo.  27,204 people in the cohort were followed prospectively from 2008-2011, of whom 8981 received the vaccine. mean age 72. primary outcome: hospitalization for pneumococcal community-acquired pneumonia (CAP), and all-cause CAP. pneumoccocal etiology determined if pos blood culture, pos sputum culture with no other likely bacterial pathogen, or positive urinary antigen test. results:     --incidence rate (per 1000 person-years) were 0.21 for bacteremic pneumococcal CAP, 1.45 for nonbacteremic pneumococcal CAP, and 7.51 for all-cause CAP.  None of these were significantly different between vaccinated and unvaccinated.     --BUT,  in those vaccinated  within the past 5 years  (n=2390)  there was a reduced risk of bacteremic pneumococcal CAP (HR=0.38, .09-1.68),

NEJM with recent article on the trend in diabetes-related complications from 1990 to 2010 (see  dm complic decrease nejm 2014  in dropbox, or DOI: 10.1056/NEJMoa1310799), comparing age-standardized incidence of lower-extremity amputation, end-stage renal disease (ESRD), acute MI, stroke, and death from hyperglycemic crisis (either DKA or hyperosmolar hyperglycemic state). results:         --acute MI: -67.8% (95.6 fewer cases per 10,000 persons per year)         --death from hyperglycemic crisis: -64.4%  (2.7 fewer cases per 10,000 persons per year)         --stroke: -52.7%  (58.9 fewer cases per 10,000 persons per year)         --amputations: -51.4%  (30 fewer cases per 10,000 persons per year)         --ESRD: -28.3%  (7.9 fewer cases per 10,000 persons per year)         --these rate reductions were first noted in 1995 and were consistent thereafter.          --the greatest decline in absolute and relative terms was in people >75 yo (except from ESRD): ie, the di

the current nejm study follows one i sent out last year from jama (see  chf preserved EF spironolactone jama 2013  or JAMA. 2013;309(8):781-791), of the Aldo-DHF, a european study looking at whether spironolactone improved diastolic function and exercise tolerance in 422 ambulatory patients with diastolic heart failure, finding an improvement in left ventricular diastolic function but no difference in maximal exercise capacity, patient symptoms or quality of life. in the current TOPCAT nejm study (see  chf preserved EF spironolactone nejm 2014  in dropbox, or DOI: 10.1056/NEJMoa1313731), 3445 pts with symptomatic diastolic heart failure (EF>45%) given low dose spironolactone (15-45mg/d) vs placebo, assessing primary outcome of cardiovasc death, aborted cardiac arrest, or hosp for heart failure. followed 3.3 years. results:     --baseline characteristics: ave age 69, half female, 90% white, LVEF 56%, 96% NYHA functional class 2 or 3,  serum K=4.3, 82% on diuretic, 84% ACE-I/

The Am Geriatrics Soc released a second set of "five things physicians and patients should question" (see  http://www.americangeriatrics.org/files/documents/5things_list_PART.pdf , or c hoosing wisely geriatrics 2014  in dropbox). the items: 1. don't prescribe cholinesterase inhibitors for dementia without periodic assessment of cognitive benefits and adverse GI effects. benefits overall are modest, impact on quality of life unclear. so give 12 weeks and stop if no significant improvement. continue with nondrug management (pt/caregiver education, diet, exercise, direct nonpharm behavioral approach depending on the specific issues). 2. not do routine screening for breast, colon, prostate cancer without considering life expectancy and risks (testing, overdiagnosis, overtreatment). esp if life expectancy less than 10 years. basically for these tests (per their numbers) need to screen 1000 patients to prevent 1 death in 10 years for each of these three tests) 3.

as per several prior blogs, there are (to me) significant problems with the new AHA guidelines for assessment/treatment of lipid abnormalities. one of my concerns is the very large number of people (esp men) over the age of 60 who meet criteria for statin therapy by these guidelines. i gave the following examples:     --60 yo white male, no known atherosclerotic disease, systolic blood pressure of 130 on meds, total cholesterol 130, HDL 70 (so LDL around 70) would qualify for moderate intensity statins     --60 yo african-american with same risk factors qualifies for high intensity     -- all men age 70 would qualify for high intensity statins,  including a white male nonsmoker with syst blood pressure of 130 and the same pristine lipids     -- a 70 yo woman with similar risk profile qualifies for moderate intensity statins. an assessment was just published of the difference between the old and new guidelines, looking at baseline data from the NHANES database of 3773 peopl

BMJ just came out with 2 articles from the Cochrane group on neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) (see  http://www.bmj.com/content/348/bmj.g2545.pdf%2Bhtml  for oseltamivir and  http://www.bmj.com/content/348/bmj.g2547  for zanamivir). these papers are updated systematic reviews, and for oseltamivir (per the editorialist) "is the culmination of a four and a half year battle for access to the raw data from industry funded trials of oseltamivir, a drug on which the world has spent billions of dollars", and reflects very different results than that presented to regulators, policy makers, the public etc by the drug makers. brief summaries: oseltamivir : 83 RCTs on adults and kids. results:     --treatment studies:             --time to first alleviation of symptoms: decreased 16.7 hours (from 7 days to 6.3 days). no effect on kids with asthma, but healthy kids decreased symptoms by 29 hours             --no diff in admissions to hospital