geoffrey modest medical blogs

There was an editorial in the NY Times 11/26/14 written by the pathologist who discovered PSA in 1970 (and writer of a book on it, called "the great prostate hoax: how big medicine hijacked the psa test and caused a public health disaster" -- see  http://www.nytimes.com/2014/11/26/opinion/the-problem-with-prostate-screening.html?ref=opinion&_r=0 ​ .  there was also a recent interview of him by Eric Topol -- see  http://www.medscape.com/viewarticle/828854_1 ​ . his basic comments: --in reviewing the European Randomized Study of Screening for Prostate Cancer (ERSPC), and the Swedish Goteberg study (which was the basis for the European one) and had a 44% reduction in prostate cancer deaths, they refused to allow outside investigators to review the data. (the 11-year followup reported in NEJM from the whole  ERSPC was 29% reduction in those adherent to the study-- see  N Engl J Med 2012; 366:981-990 ) --there were inherent concerns about about the methadology, inclu

the Endocrine Society just released clinical practice guidelines for the diagnosis and management of Paget's disease of the bone (see  pagets clin pract guideline endo society 2014 in dropbox, or go to URL:  http://press.endocrine.org/doi/pdf/10.1210/jc.2014-2910 ). some background: there is a genetic component with family history in 10-20% and autosomal dominant transmission pattern, clinically rare prior to age 40, men and women affected. basic recommendations: Diagnosis --in patient with suspected paget's, get plain xray of suspected area. if diagnosed with paget's, then get radionuclide bone scan to assess extent of disease --if diagnosed with paget's by xray, get biochemical evaluation: alkaline phosphatase (ALP) or more specific marker of bone formation (especially if there is hepatobiliary disease which could affect the ALP) – can check amino-terminal propeptide of type 1 collagen (P1NP, the best option but expensive) or bone-specific ALP (though t

it has been shown in several studies that gastric acid suppression puts people at risk for several infections, including pneumonia, c difficile, and  gastroenteritis . In fact, one of the predisposing conditions to developing disseminated TB infection is post-gastrectomy, presumably because stomach acid inhibits TB dissemination (there are several reports in the literature, mostly case-controlled studies, finding that acid suppression also is associated with TB infections). well, not to shock you all, but it turns out that acid suppression leads to significant changes in the gut (gastric bacterial overgrowth) as well as the lung microbiome (see  microbiome changes with acid suppression JAMA Peds 2014 in the dropbox, or doi:10.1001/jamapediatrics.2014.696​). this study was a 5-year prospective one in kids aged 1-18 yo who were getting bronchoscopy and endoscopy to evaluate chronic cough, with a questionnaire about used of acid-suppressant medications. the researchers assessed the diffe

Although the data on HDL being protective of atherosclerotic disease is pretty consistent, there are negative studies, and the data on medications which dramatically improve HDL levels (eg, the cholesteryl ester transfer protein --CETP --inhibitors, such as torcetrapib) are clinically disappointing. there have been several explanations for this. for example, some HDL particles are "pro-inflammatory" and elicit an atherosclerotic response (which may be related to apolipoprotein C-III). a new article in NEJM highlights another angle -- that the issue is not the HDL number, but HDL's functionality in the reverse transport of cholesterol, as measured by the cholesterol efflux capacity (see  lipids HDL efflux capacity vs amt NEJM 2014 in dropbox, or  DOI: 10.1056/NEJMoa1409065). This article looks at the Dallas Heart Study, where they measured HDL levels, HDL particle concentrations, and cholesterol efflux capacity in 2924 adults free of cardiovascular disease and followed p

a remarkably​ common clinical situation is the patient with coronary artery disease (CAD) who develops atrial fibrillation. do you keep the aspirin (ASA) or other antiplatelet therapy (APT) when starting oral anticoagulants (OAC) such as warfarin??? in theory, these are 2 very different drugs targeting 2 different ongoing mechanisms: aspirin and other APTs inhibit platelets and arterial clots, acute coronary syndromes (ACS), etc; warfarin and other OACs inhibits blood coagulation which interferes with venous clots and venous thrombosis, pulmonary embolism, etc. but there is clearly a higher risk of bleeding if the combo of OAC and APT are used. The ORBIT-AF registry trial (see  aspirin and warfarin in afib cad ORBIT HF circ 2012 in dropbox, or doi: 10.1161/CIRCULATIONAHA.113.002927), looked at 10126 patients from 176 US practices, found that the combination of ASA and OAC was common (35% of patients), that 39% had no history of documented atherosclerotic disease, and that there was a

There are good data suggesting that ACE inhibitors (ACE-I) are important in patients post STEMI (ST-segment elevated myocardial infarction) and are recommended therapy. however, no data are available on the role of angiotensin receptor blockers (ARBs), which are typically used for other ACE-I indications in the 15-20% of patients intolerant of ACE-I. A prospective Korean cohort study was just published in BMJ looking at their post STEMI treatment, assessing the outcomes of 6698 patients from 53 hospitals, all of whom had primary percutaneous coronary interventions (PCI) and LV ejection fractions >40%, of whom 1185 (17.7%) were given ARBs, 4564  (68.1%) given ACE-I and 949 (14.2%) neither (see MI preserved EF ARB bmj 2014 in dropbox , or doi : 10.1136/ bmj.g6650 ). median followup of 371 days. this study involved propensity scoring, a technique used in nonrandomized trials to mathematically compensate for covariates that could have influenced treatment allocation (in this case,

an interesting article found that placebo was more effective than no treatment in kids with cough ( see  placebo for cough in kids JAMA peds 2014 ​ in dropbox, or doi:10.1001/jamapediatrics.2014.1609). this was a 13 month study in 2 outpatient pediatric practices of kids aged 2-47 months who had nonspecific acute cough of less than 7 days. parents were given surveys the day before and after the allotted treatment, which was either pasteurized agave nectar, caramel-colored placebo (each given 30 minutes prior to bedtime), or "no treatment". all parents were instructed in routine care of the child: hydration, saline nasal spray, and use of acetaminophen/ibuprofen as needed (ie, the "no treatment" group did get treatment, just not a teaspoon of "meds"). the survey assessed cough frequency, cough severity, congestion severity, rhinorrhea severity and the cough effect on child and parent sleep. results: ​ --119 children completed the study, mean age 23 m

it has been shown in several studies that gastric acid suppression puts people at risk for several infections, including pneumonia, c difficile, and  gastroenteritis . In fact, one of the predisposing conditions to developing disseminated TB infection is post-gastrectomy, presumably because stomach acid inhibits TB dissemination (there are several reports in the literature, mostly case-controlled studies, finding that acid suppression also is associated with TB infections). well, not to shock you all, but it turns out that acid suppression leads to significant changes in the gut (gastric bacterial overgrowth) as well as the lung microbiome (see  doi:10.1001/jamapediatrics. 2014.696​). this study was a 5-year prospective one in kids aged 1-18 yo who were getting bronchoscopy and endoscopy to evaluate chronic cough, with a questionnaire about used of acid-suppressant medications. the researchers assessed the difference in concentration and prevalence of bacteria in the stomach and lung,

4.4 million colonoscopies were performed in Germany since October 2002 as part of a national, government-sponsored initiative (and covered by their Statutory Health Insurance, with a federal registry of the findings), on people aged 55-80. they assessed mortality, the overall age- and sex-specific findings, and projected the numbers of colorectal cancers (CRCs) prevented, those detected earlier than would have been without screening, and the extent of overdiagnosis  (see  colonoscopy 10 yr german study clinical gastro hepat 2014  in dropbox,or doi.org/10.1016/j.cgh.2014.08.036). ​ lifetime risk of CRC in Germany is approx 7.5% in men and 6.1% in women. results: --22% of eligible women and 20% of eligible men had a screening colonoscopy in the initial 10 year period --at least one neoplasm (adenoma or cancer) was found in 28.5% of men and 17.6% of women --CRCs prevention: 180,000 (1 in 28 screening colonoscopies) --CRCs detected earlier by screening:  40,000  (1 in 121 s

Circulation had a recent article on the prevalence of orthostatic hypotension in Ireland (see  hypotension orthostatic with age circ 2014​ ​ in the dropbox, or  doi:10.1161/CIRCULATIONAHA.114.009831 ​). This study involved 4475 community-based people over age 50 from a nationally representative cohort study (TILDA -- The Irish Longitudinal Study on Ageing -- that's how they spell "aging"...), recording blood pressure and pulse response to standing. they looked at initial orthostatic hypotension, defined as a BP decrease of >40 mmHg systolic or >20 mmHg diastolic within 15 seconds of standing and associated with symptoms of cerebral hypoperfusion, and typical orthostatic hypotension, defines as a BP decrease of >20 mmHg in systolic or >10 mmHg in systolic after 3 minutes of standing. Findings: --Cohort baseline characteristics: average age 62.8, 51.8% female, 19% smokers, 7.5% diabetes, 34.5% hypertensive, total of <11% with any cardiovascular history --

so, yesterday Medicare proposed paying for lung cancer screening by low dose CT (LDCT) scans, though a somewhat less aggressive and better-conceived recommendation than that of the US preventive task force (USPSTF). (the Medicare proposal is still open to public comment for 30 days, but unlikely to change). the private insurers are locked-in legislatively (through the Affordable Care Act) to comply with the USPSTF recommendations by January 1, 2015, but Medicare has equivocated until now. The proposed recommendations for all Medicare beneficiaries who have at least a 30 pack-year history of smoking and is either a current smoker or has quit in the past 15 years: --those aged 55-74 (vs 80 in USPSTF) would be entitled to annual LDCT screens. (the lower age would apply to those 480,000 Medicare beneficiaries under age 65 who get Medicare for certain disabilities). this would be yearly until either age 75, or if the person has quit smoking for 15 years (presumably based on older studies

the Am College of Physicians just released a clinical practice guideline on interventions to prevent recurrent kidney stones (see  kidney stone secondary prevention AIM 2014 in dropbox, or  doi:10.7326/M13-2908 ​). background: --13% of men and 7% of women get kidney stones, and 35-50% have recurrence within 5 years without treatment --80% are calcium oxalate or calcium phosphate or both --dietary efforts include increasing water intake, reducing dietary oxalate, reducing dietary animal protein and other purines, and maintaining normal calcium intake results of this systematic review: --1 good quality and 28 fair-quality trials found insufficient evidence that assessing stone composition, or blood/urine chemistries reduces recurrences --80 fair-quality trials of dietary interventions have found that:          --increased fluid intake, reduced soft drink intake (esp soda acidified by phosphoric acid, eg colas), and a high-calcium, low-protein, low-sodium diet

there was an important editorial in the NY Times today on governmental ineffectiveness in regulating industrial chemicals (see  http://www.nytimes.com/2014/11/10/opinion/making-chemistry-green.html?emc=edit_th_20141110&nl=todaysheadlines&nlid=67866768&_r=0). the potential effects are profound and not significantly different from data i saw in the early 1970s. --there are 84,000 chemical compounds in commercial use, with 500-1000 new ones introduced annually --in an analysis of 143,000 peer-reviewed research papers, it takes an average of 14 years from the time safety issues are raised and action taken (while the chemicals remain in the market) --the case in point in the article is the use of triclosan and triclocarban, ubiquitous environmental contaminants used in anti-bacterial soaps, cosmetics and other consumer products for the past 40 years. --these chemicals are from the same class as "persistent, bioaccumulative and toxic compounds known as organ