geoffrey modest medical blogs

of all of the new diabetes meds, the one i am most impressed with is exenatide. mostly because the long-acting preparation is injected only once a week, has studies showing it is at least as good an effect as lantus in patients without endstage diabetes, and is pretty physiologic (stimulates postprandial insulin release and decreases appetite, so unusual to be hypoglycemic and tend to lose weight). that being said, none of the new meds have real clinical outcome data, just surrogate marker of A1C improvement (as does rosiglitazone, which we know is associated with increased heart disease). one concern with GLP-1 agonists such as exenitide is that a couple of studies suggested increased risk of pancreatitis, and even some concern about pancreatic cancer. in this light, the FDA and EMA (european medicines agency) independently investigated and came out with a safety assessment (see  dm exenatide and pancreatitis FDA statement 2014  in dropbox, or DOI: 10.10...

so, just after i sent out the neurology association recommendations on anticoagulation for nonvalvular atrial fibrillation, i found this article -- which looked at patients who had lacunar strokes while already on aspirin to see if adding clopidogrel helped  (see  stroke clopid plus asa not help if on asa neuro 2014  in dropbox, or DOI 10.1212/WNL.0000000000000076).  this is a post-hoc analysis of patients with aspirin failure and recent lacunar stroke in the larger SPS3 study (secondary prevention of small subcortical strokes trial). --SPS3 involved 3000 patients with recent (<180d) symptomatic lacunar stroke with ipsilateral carotid artery disease not amenable to surgery, then all received aspirin 325mg/d and were randomly assigned to get additional clopidogrel vs placebo. this present study looked at the group (secondary analysis) of 838 patients who had been on aspirin prior to the lacunar stroke (the aspirin failure group) to see if those put on asp...

am acad of neurology just published new guidelines on stroke prevention in patients with nonvalvular atrial fib  (see  afib anticoag neuro guidelines 2014  in dropbox, or DOI 10.1212/WNL.0000000000000145). their findings:     --in patients with cryptogenic stroke, most studies used Holter monitoring, followed by serial EKGs, event monitors, etc, with monitoring duration from 24 hrs to 30d. pickup of nonvalvular afib (NVAF) was 0-23%, average 10.7%. increased pickup with increased duration of monitoring.     --INR goal for warfarin therapy is 2-3     --non-warfarin therapies: dabigatran is "probably more effective" than warfarin. hemorrhage risks similar, though less intracranial hemorrhage and more GI bleeds. rivaroxaban is "probably as effective as warfarin", no diff in risks of bleeds (also more GI and fewer intracranial). apixaban "likely more effective than warfarin", with decreased bleeding and reduced mortality. oral antic...

the am acad of pediatrics just came out with new pediatric preventive care guidelines (see pedi preventive health recs 2014 in dropbox, or go to  http://pediatrics.aappublications.org/content/early/2014/02/18/peds.2013-4096.full.pdf ).  the guidelines are basically a chart of either things to do on all kids, or targeted assessments -- risk assessment with appropriate action to follow if positive. the basic changes are: development/behavior:          --depression screen yearly from ages 11 through 21, esp using PHQ-2       --alcohol and drug screen yearly from ages 11 through 21, esp using CRAFFT (this is to do targeted assessment, with appropriate action if positive) procedures:           --lipid screening: targeted at age 24 mo, 2 y, 4 y, 6 y, 8 y, then once for all kids aged 9-11 y (this is the new recommendation), then targeted annually from 12-17 y, then again once for all kids aged 18-21 ...

Just after my sending out an article on aspirin in primary prevention of heart and other diseases, JNCI  has conveniently published an assessment of aspirin and ovarian cancer (see  aspirin and dec ovarian cancer jnci 2014  in dropbox, or DOI:10.1093/jnci/djt431). in this study the Ovarian Cancer Association Consortium reviewed the literature, finding 12 population-based case-controlled studies between 1992 and 2007, which included 7776 patients with ovarian cancer and 11,843 control subjects.  Findings:             --Overall ovarian cancer risk was reduced 9% with the use of aspirin             --Non-significant but similar reduction was found for non-aspirin NSAIDs, and no association with acetaminophen use             --7 studies assessed the frequency of aspirin use, finding that risk re...

New study in JNCI attempted to sort out diverse findings on prostate cancer development in men supplemented with selenium or vitamin D or both.  ( see prostate cancer selenium vit e jnci 201 4  in dropbox, or DOI : 10.1093/jnci/djt456).  Previous data has shown:           --From the selenium and vitamin E cancer prevention trial (SELECT) in 2001, a prospective study of 35,533 men randomized to one of 4 groups (selenium 200 mcg/d plus vitamin E 400 IU/d, vitamin E plus placebo, selenium plus placebo, or just placebo),  there was no  benefit from these interventions, and a significantly increased risk of prostate cancer by 17% with vitamin E supplementation alone         --The nutritional prevention of cancer trial (NPC), a study of 928 men who lived in an area of the US with low soil selenium levels, found that men with moderate or low selenium levels and given supplementation with ...

NEJM just came out with review article on lung auscultation ( see  lung auscultation nejm 2014  in dropbox, or  DOI: 10.1056/NEJMra1302901 ) .  it does seem that we are moving towards using echocardiograms instead of cardiac auscultation, bolstered by studies confirming that cardiologists ain't so great at predicting whether a murmur is from the right or left side of the heart. and, seems that at the slightest hint of lung problems, CTs are the way to go. although i am being a tad sarcastic, my sense is that medical students/residents/perhaps some of the younger attendings are not as fluent as some of us more traditionally-trained ones (a euphemism for older ones....) so, will circulate this article. a few points: --some of the nomenclature has evolved over the years. for better or worse, rales don't exist anymore. just crackles. and "moist" vs "dry" is out (turns out that one person's moist is another's dry, and neither seemed to correlate with...

JAMA this week reported on the use of citalopram for agitation in people with Alzheimer's disease (see alzheimer agitation citalopram jama 2014 in dropbox, or doi:10.1001/jama.2014.93). details:     --double-blind study of 186 pts with probable alzheimer's and agitation (mean age 78, 46% women, 65% white, 70% on cholinesterase inhibitor and 42% on memantine) at 8 US and Canadian academic sites, all with 9 week psychosocial intervention, half with citalopram (began at 10mg, titrated up to 30mg over 3 weeks, and with 78% achieving the 30mg target). psychosocial intervention consisted of giving educational material, 24-hr availability for crisis management, and 20-30 minute counseling session at each visit, focusing on reviewing/adjusting supportive care plan, providing emotional support, counseling regarding specific caregiver skills, and assistance with problem solving on specific caregiver/patient issues.  At 9 weeks:     --18-point Neurobehaviora...

I had sent out a couple of articles in the lancet suggesting that aspirin protected against incident cancer and cancer mortality, including in those with metastatic disease (see  aspirin and incident cancer lancet 2012 and  aspirin cancer mets lancet 2012  in dropbox). New observational study of 6000 men with prostate cancer (localized adeno, rxd with radical prostatectomy or xrt) and followed 70 months found that, irrespective of the prostate ca therapy, those who happened to be taking aspirin had much lower prostate-specific mortality (3% vs 8%), with dec in both disease recurrence and bony mets. The decrease was particularly impressive in those with "high-risk" disease, wtih prostate-specific mortality 4% vs 19%. Although they looked at all anticoag therapies, the effect was primarily seen with aspirin.  See  aspirin and prostate cancer jco 2012  in dropbox.  So, observational study, but adds to the lancet studies, and prior studies that aspirin/ns...

Lancet also had 2 articles on aspirin and cancer (both from same group in UK).  This is the same impressive group that did a whole lancet issue a few years ago on blood pressure variability and stroke (in the dropbox and my power point presentation on hypertension)   1. looked at 5 trials using aspirin, at least 75mg/d, to decrease vasc events, with 6.5 yrs followup.  Many old studies suggested dec in colon ca with asa or nsaids, most with positive results. This study of 17K pts found 36% dec risk of distant mets overall in pts with cancer, with the vast majority of effect in adenoca -- 48% dec risk of metastases in those with adenoca. Esp effective in those without mets at diagnosis (50% decrease). Essentially all of the graphs show continuing divergence of curves for the first approx 8 years, then plateauing, for lung, bone, brain, and other mets.  The total number of cancers detected and elligible for analysis was 775. (they do not give absolute risk reductio...

a recent article reviewed the data on the use of aspirin in  primary prevention, both cardioprotective and chemoprotective (see  cad aspirin primary prevention eur hrt j 2013  in dropbox or doi:10.1093/eurheartj/eht058). basically, no new data challenging the old recommendations for primary and secondary prevention of vascular disease: for secondary prevention there is a 20% decreased risk of vascular complications, translating to an absolute reduction of 10-20/1000 pts in annual incidence of nonfatal events (smaller but important reduction in vascular deaths),with absolute increase in major extracranial bleeding complications which is 20-50 fold smaller.  the data on primary prevention is not so impressive. studies difficult to meta-analyze, since different populations and different endpoints. but overall, data insufficient to advocate either for or against aspirin use. and there are some data that in certain conditions (eg following CABG, pts with essent...

new guidelines (they just keep comin'...), this time on defn, eval and treatment of severe asthma (see  asthma severe treatment euro resp j 2014 ,  or   DOI: 10.1183/09031936.002020), put out by combo of european respiratory society and american thoracic society. main points: definition: severe asthma (approx 5-10% of asthmatics) = asthma requiring high dose inhaled steroids (ICS) plus second controller (eg ICS plus long-acting b-agaonist (LABA) or leukotriene modifier/theophylline) for the past year and/or systemic steroids (>50% of the time in the past year) to control, or remains uncontrolled despite this therapy (uncontrolled = poor symptom control, or >=2 bursts of systemic steroids in past yr, or at least one hospitalization in past yr, or FEV1<80% after appropriate bronchodilator withhold.  only after confirm asthma dx -- see evaluation section [there is an extensive section on phenotyping asthmatic kids and adults, which seems to reflect age o...

25-year results fro the Canadian National Breast Screening Study just published in BMJ open access (see  mammog canadian study bmj 2014  in dropbox, or  doi: 10.1136/bmj.g366 ), finding no benefi t from mammog screening an d that  22% of mammog-detected breast cancers were overdiagnosed!!  lots of data from the study, will include since  allows a more critical understanding.   study methodology:         --15 screening sites in Canada assigned 90K women aged 40-59 randomly to mammog (5 annual mammos) or control, ending in 1988          --all women had clinical breast exam  (CBE)  and  were  taught self-exam          --women 40-49 received an initial mammo, then randomized  (irrespective of clinical exam) to annual  (ie, another 4) plus CBE  vs no mammog /just usual care    ...

new article looked at timing to suturing lacerations and outcome (see   wound suturing timing emerg med 2014  in dropbox,  or   doi:10.1136/emermed-2012-202143 ) .  they assessed 2700 consecutive patients after suturing traumatic lacerations,  with results:   --69 developed wound infections (not surprisingly these people had less good cosmetic outcome, occ needing scar revision) --predictors for infection were largely the usual suspects:         --diabetes (RR 2.70)         --contaminated lacerations (RR 2.0)         --lacerations longer than 5 cm (RR 2.9)         --lower extremity lacerations (RR 4.1) --and,  not  associated with increased infection rate         --deeper lacerations requiring deep stitches --suturing after 12 hours vs <12 h,...

American Heart Assn and American Stroke Assn just published 44-page, highly referenced guideline for stroke prevention in women, noting that there are both unique female risk factors (eg preeclampsia, oral contraceptives, menopause and hormone replacement) as well as other risk factors that are more common in women (obesity/metabolic syndrome, atrial fibrillation, migraine with aura). see  stroke prevention women guidelines AHA 2014  in the dropbox, or   DOI: 10.1161/01.str.0000442009.06663.48.    they note: --stroke more common in women (53.5% occur in women, with  3.8 million women and 3 million men now living after having had a stroke), and is the 3rd leading cause of death (fifth for men) --the increased incidence in women is likely to get worse, with an aging population and increased longevity of women --the types of stroke differ some: overall 87% of strokes are ischemic, and men have more ischemic strokes than women (the exception being in t...

NY times article today on dabigratin, or Pradaxa. (see  http://www.nytimes.com/2014/02/06/business/study-of-blood-clot-drug-pradaxa-unnerved-its-maker-documents-suggest.html?ref=todayspaper  ).  i don’t mean to shock anyone, but yet again a drug company massaged the studies, withholding important information because it could affect marketing (sounds like a  gabapentin replay?). this time it was the company making dabigratan (marketed as an anticoagulant for atrial fib, which, unlike warfarin, does not require blood tests/monitoring). turns out that there probably is a safe blood level, and those below that level clot and those above it bleed, causing approx 1000 deaths so far.  Belies their claims (and their major niche in the market) that no monitoring needed..... so, you can’t always believe what you read, as well as what you can’t read

The CARDIA study of 3442 black and white men and women aged 18-30 in 4 cities (Birmingham AL, Chicago IL, Minneapolis MN, Oakland CA) were followed 25 years (1985-2010), and were assessed for BP measured at baseline, 2,5,7,10,15,20, and 25 years, then evaluated for subclinical CAD by their coronary artery calcification (CAC), perhaps the best predictor of atherosclerotic disease (confirmed in the recent AHA guidelines) --  (see  htn young and CAD middleage jama 2104  in dropbox, or doi:10.1001/jama.2013.285122). they assessed 5 different BP trajectories, with the following adjusted odds ratios for high CAC score (comparing the 4 other categories with the low-stable cohort): --low-stable bp (19.9% of population), with SBP 101-104, DBP 62-64 over the 25 yrs -- this group had an elevated CAC score developing in 5.8% --moderate-stable (42.3%) , with SBP 109-118, DBP 68-74 over the 25 yrs  -- odds ratio 1.44, with absolute increase above the low-stable group of 2.7...

here is the Jan 31 FDA alert about testosterone (also see link:  http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm384225.htm ): AUDIENCE : Cardiology, Urology, Family Practice ISSUE : FDA is investigating the risk of stroke, heart attack, and death in men taking FDA-approved testosterone products. We have been monitoring this risk and decided to reassess this safety issue based on the recent publication of two separate studies that each suggested an increased risk of cardiovascular events among groups of men prescribed testosterone therapy. FDA is providing this alert while it continues to evaluate the information from these studies and other available data. FDA will communicate final conclusions and recommendations when the evaluation is complete. BACKGROUND : Testosterone is a hormone essential to the development of male growth and masculine characteristics. Testosterone products are FDA-approved only for use in men who lack or h...