geoffrey modest medical blogs

JAMA  just published a systematic review and meta-analysis of the medical use of cannabinoids (see  cannabis medical use  jama  2015 , or  JAMA . 2015;313(24):2456-2473.). This is rather timely as several states are moving forward implementing new procedures for use of medical marijuana (as of may 2015, 23 states and Washington DC). The researchers evaluated 79 studies with 6462 participants. Details: --Nausea/vomiting from chemotherapy: 28 studies, most with high risk of bias. -all studies showed cannabinoid benefit (some not reaching statistical significance), whether vs placebo or active comparator ( procholorperizine , chlorpromazine,  domperidone , and with single studies on  alizapride , hydroxyzine, metoclopramide and  ondansetron )         -cannabinoids vs placebo: also higher average number of patients showing complete response with cannabinoids [OR 3.82 (1.55-9.42); 3 trials] --Appetite stimulation in HIV infection. 4 studies, all at high risk of bias -some evide

a rather unusual quick-and-dirty study was just published looking at the relationship between metformin use and mortality, as well as lactic acidosis, in those with severe chronic kidney disease, CKD. This study was based on a window of time until 2009, when metformin was used  in Taiwan  without restriction in those with renal disease (See dm  metformin  ckd  death lancet 2015  in  dropbox , or  doi.org /10.1016/ S2213 -8587(15)00123-0). The researchers looked at a large database of diabetics with severe CKD -- (those with diabetes plus a primary diagnosis of chronic kidney disease and those receiving erythropoiesis-stimulating agents, which was prescribed for 85% of non-dialysis patients with stage 5 chronic kidney disease --ie,  GFR<15 ml/min), and compared outcomes of those who were prescribed metformin to  a propensity-match scored group of patients not on metformin (a mathematical tool to attempt to adjust for patients with similar levels of comorbidities), and looked at outc

as a followup to my recent blog on the CDC guidelines for sexually-transmitted diseases (see  http://gmodestmedblogs.blogspot.com/2015/06/new-std-treatment-guidelines.html  ), there was a recent study looking at Mycoplasma genitalium resistance in the Netherlands (see  STD m genitalium resistance jantimicchemo2015 ​ in dropbox, or doi:10.1093/jac/dkv136). and this comes right after the comment from prior my blog noting that M genitalium  " does respond to 1-g single dose of azithromycin (though resistance is emerging) ". (I will highlight the section on M genitalium below, since it seems to becoming an increasingly important actor on the STD stage). details of the Netherlands study: --​they looked at all urogenital samples from Feb 2012 to Nov 2014 in the east of the Netherlands to identify the frequency of gene mutations associated with macrolide-resistance --44 of the 146 samples (30.1% overall, from  55 males and 91 females) had 1 of 3 mutations associated with macr

A study just published looked at tenofovir disoproxil fumarate (TDF) renal toxicity, finding that urine dipstick evaluation is inadequate (see  hiv tenofovir nephrotoxicity AIDS2015  in dropbox, or AIDS 2015, 29:941–946). details: --43 patients with TDF nephrotoxicity (mean age 54.7, 53% men, 37% white/32% african-american/19% latino), and having biopsies showing proximal tubular injury and typical mitochondrial abnormalities for TDF nephropathy. Median duration of TDF therapy was 9.5 months, with the earliest case after 2 weeks. Baseline serum creatinine 1.2 mg/dl, increasing to 4.9 after the TDF. --results:         --37 cases reported proteinuria by dipstick, 60% of these cases had at least 2+  proteinuria  ​(8% 0-trace, 32% 1+) -- note: the dipstick proteinuria primarily measures albuminuria.         --27 patients had urine protein quantified (either 24-hour collection or spot urine protein-to-creatinine ratio), median proteinuria was 1742 mg/day -- note: this is total pr

there have been a couple of well-publicized studies finding that arthroscopic knee surgery for degenerative joint disease/osteoarthritis (OA) is not beneficial. however, there continues to be uncertainty, and "many specialists are convinced of the benefits of the procedure from their own experience".  in the US, 700K knee arthroscopies are done each year, and this number seems to be increasing. in this light, there is a welcome systematic review and meta-analysis just published  (see  knee arthritis arthroscop surgery bmj2015  in dropbox, or doi:  http://dx.doi.org/10.1136/bmj.h2747  ).  details, for the 9 studies evaluated: --1270 patients in total, receiving arthroscopic surgery with partial meniscectomy, debridement or both, vs control (sham surgery or exercise) --mean age in the studies was 49.7-62.8. mean baseline pain (visual analog scale of 0-100mm) ranged from 36-63 mm. --2 trials only had patients with radiologic OA (Kallgren and Lawrence grade 2 or more); 5

the Lancet just published an article on the trends of atrial fibrillation (afib) over the past 50 years, based on the meticulous Framingham Study database  (see  afib  prevalence framingham  lancet 2015  in  dropbox , or  doi.org /10.1016/ S0140 -6736(14)61774-8). they looked at 9511 study participants from 1958-2007, assessing  afib  prevalence, incidence, risk factors and mortality over 10-year blocks, stratified by sex, with 202,417 person-years of observation.  results: --there were 1544 cases of new-onset  afib  (821 men and 723 women) --between the first and last 10-year groupings         --the age-adjusted  prevalence  of  afib  quadrupled from 20.4 to 96.2 per 1000 person-years in men, and from 13.7 to 49.4 cases per 1000 person-years in women  (p<0.001)         -- the age-adjusted  incidence  of  afib  went from 3.7 to 13.4 per 1000 person-years in men, and from 2.5 to 8.6 cases per 1000 person-years in women ​ (p<0.001)         --for EKG-diagnosed  afib , f

There was a recent article published online and hitting the press regarding a possible association between the use of proton-pump inhibitors (PPIs) and subsequent MIs  ( see  PPI and MI PLoS 2015  in dropbox, or DOI:10.1371/journal.pone.0124653​). The article was unusual in that it used a new technique for medical research: data-mining.  The bottom line is that if there were a real association between PPI use and MIs, this would have profound medical implications, since over 113 million PPI  scripts  are filled annually around the world  with  over $13 billion in sales, and in the US in 2009 21 million people filled at least one PPI script (the 3rd highest seller in the US). details: --they looked at over 16 million clinical documents on 2.9 million people to assess PPI use and cardiovascular risk. There were 2 large data sources for the data mining (Stanford, and Practice Fusion, Inc) and one prospective source for a survival analysis. For the data-mining, they electronically eva

There was a recent article published online and hitting the press regarding a possible association between the use of proton-pump inhibitors ( PPIs ) and subsequent MIs  ( see  DOI:10.1371/journal.pone. 0124653​). The article was unusual in that it used a new technique for medical research: data-mining.  The bottom line is that if there were a real association between  PPI  use and MIs, this would have profound medical implications, since over 113 million  PPI   scripts  are filled annually around the world  with  over $13 billion in sales, and in the US in 2009 21 million people filled at least one  PPI  script (the 3rd highest seller in the US). details: --they looked at over 16 million clinical documents on 2.9 million people to assess  PPI  use and cardiovascular risk. There were 2 large data sources for the data mining (Stanford, and Practice Fusion, Inc) and one prospective source for a survival analysis. For the data-mining, they electronically evaluated clinic notes to sea

The Veterans Affairs Diabetes Trial (VADT) was one of the triumvirate published around 2009, along with the ACCORD and ADVANCE trials, which looked at intensive glycemic control and cardiovascular outcomes. These trials basically found that intensive control did not help and perhaps hurt: the ACCORD trial achieved an A1c of 6.4% in the intensive group vs 7.5% in the standard group, but had no benefit overall for nonfatal MI, nonfatal stroke and cardiovascular disease (CVD) deaths and actually had a 22% increased mortality after 3.5 years; the ADVANCE trial achieved an A1c separation of 6.3% vs 7.0% and found no macrovascular or mortality benefit after 5 years; and the VADT achieved an A1c separation of 6.9% vs 8.5% and found no CVD or mortality benefit after 5.6 years.  The current study looked at VADT outcomes in the 1791 military veterans after 11.8 years of followup, up to 5 years after the study ended (see  dm tight control VADT followup nejm 2015  in dropbox, or N Engl J Med 2015

there was a rather poignant editorial in the NY Times on June 8th, pointing out 2 clever (though, incidentally, illegal) ways the drug companies help boost their profits by preventing/delaying the transition to generics: 1. buying off the competition -- the example of Provigil: the drug company (Cephalon) first sued 4 generic drug makers for "patent infringement", then paid them >$300 million to drop their challenge to Provigil's patent (it turns out that Teva, one of the generic drug makers, ultimately bought out Cephalon, and the Federal Trade Commission made them pay $1.2 billion for Cephalon's scheming) 2. drug company pulling a drug from the market which had an upcoming patent expiration, replacing it with newer formulation, and spending lots of $$ to get doctors and patients to change to the new formulation (example of Namenda for Alzheimer's, reformulated as a once-a-day drug, so pharmacies cannot substitute a generic for it. And removing the older one f

New  Engl  J of Med just had a large study on the cardiovascular effects of  sitagliptin  (see  dm   sitagliptin   cardiovasc   nejm  2015  in  dropbox , or  DOI : 10.1056/ NEJMoa1501352 ). Background:  sitigliptin  is a  DPP -4 inhibitor ( dipeptidyl  peptidase 4 inhibitor), which functions by decreasing the degradation of  incretins  (and thereby increasing glucose-mediated endogenous insulin secretion and suppressing glucagon levels). But there were concerning studies with other  DPP -4 inhibitors being associated with increased risk of hospitalization for heart failure ( saxagliptin  was associated with 27% increase in the SAVOR- TIMI  study,  aloglipitin  with a  nonstatistically  significant increase in EXAMINE study). Details of the new study (drug company sponsored): --14,671 patients from 673 sites in 38 countries were randomized to adding  sitagliptin 100mg /d ( 50mg  if  eGFR  30-50) vs placebo to existing therapy. Followed 3 years --median age 66, 30% female, 68% whi