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Archive for December, 2014

Primary Care Corner with Geoffrey Modest MD: Orthostatic hypotension

18 Dec, 14 | by EBM

By: Dr. Geoffrey Modest

Circulation had an article on the prevalence of orthostatic hypotension in Ireland (see 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:BP

–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 pretty healthy

–Initial orthostatic hypotension in 32.9% of those >50yo, no difference by age or gender

–Typical orthostatic hypotension in 6.9% overall, increasing from 4.2% in 50 yo to 18.5% in those >80yo

–Prevalence of failure to return to baseline blood pressure after standing 40 seconds increased with age: from 9.1% in 50 yo to 41.2% in those >80yo

So, a few points.

  1. The pathophysiology and epidemiology of initial orthostatic hypotension is somewhat different from the typical orthostatic hypotension. With initial orthostatic hypotension, there is a rapid temporal mismatch between cardiac output and vascular resistance. This typically happens in thin young people (who need to dangle their legs prior to getting out of bed, for example) and those on a-blockers (including reports with tamsulosin for BPH). The typical orthostatic hypotension results from standing, pooling of blood in the legs, decreased venous return, which usually triggers a baroreceptor reflex inducing vasoconstriction (so the the usual change is a decrease of about 5 mmHg systolic and a slight increase in diastolic, which rapidly reverses with rapid vasoconstriction). but without this vasoconstriction, there is subsequent decrease in cardiac output and hypotension. This tends to happen in older people who have diminished baroreceptor responsiveness, and in those with hypovolemia, on aggressive diuretics, tricyclic antidepressants, etc.
  2. I don’t want to overinterpret this study. The population studied was racially and ethnically pretty uniform. There was no information on whether there was a difference if they had underlying hypertension or what medications they were taking​. and there are no data on whether the typical orthostatic hypotension was symptomatic. And the limited data available do not all point to asymptomatic hypotension as a cause of falls, for example. BUT, to me, these numbers are very impressive. I do typically check orthostatics on my elderly patients and very often do find marked hypotension on standing, sometimes symptomatic and sometimes not. when the patient is symptomatic (either by history at home, eg when standing, or in the office), I do not hesitate to back off on BP meds (or if they are not on them, I sometimes need to use fludrocortisone and high salt diets to raise the blood pressure). in asymptomatic patients, the decision is harder. In general, I am pretty concerned that they may have an even more exaggerated hypotensive orthostatic response if they are a little dehydrated (hot summer day), or don’t drink their usual amounts of fluids, or even postprandially, when blood pressure tends to be lower. It is also impressive that symptomatic initial orthostatic hypotension happens in about 1/3 of the patients over 50 yo. So, seems reasonable to ask specifically about that, as well as falls…

So, my approach is that if the blood pressure really drops on standing (eg a systolic less than 120), I do back off on blood pressure meds even if the patient is asymptomatic. Given the lack of data in the elderly that a lower systolic is beneficial (perhaps because the studies did look at lower blood pressures, leading JNC8 to suggest a target of 150/90), seems like the better part of valor to back off on blood pressure meds.

Primary Care Corner with Geoffrey Modest MD: Intensive glucose control and heart disease

18 Dec, 14 | by EBM

By: Dr. Geoffrey Modest

The Lancet recently had a posthoc analysis of the ACCORD trial, finding that decreasing A1C in type 2 diabetics was associated with decreasing ischemic heart disease events (see Lancet 2014; 384: 1936–41). This was one of 3 contemporary trials of intensive vs standard control of diabetics — neither ADVANCE nor VADT studies showing benefit of intensive diabetic control for macrovascular complications, and ACCORD actually found an increase in mortality in the intensive group.

The trial:

–10251 patients, mean age 62, with diabetes on average of 10 years, and all with high risk for heart disease and 35% with known CAD (coronary artery disease), and baseline A1C of 8.1% (this trial also had blood pressure and lipid trials embedded). No difference in # on statins (88%) or aspirin (76%).

–Intervention: keep adding meds to achieve an A1C of 6.0% in intensive group vs 7-7.9% in standard group

–The achieved A1C was substantially different in the intensive group (6.4%) vs standard (7.5%)

–To achieve this difference: 77% vs 55% on insulin, 91% vs 58% on thiazolidinediones (TZDs). Although not highlighted in this article or most of the others I’ve seen on the ACCORD study, rosiglitazone was almost always the TZD of choice!!.

–The trial was terminated early, after 3.5 years, because of a 22% increase in mortality overall

Post-hoc analysis results:  The 5-year incidence of

–Ischemic heart disease 13% lower in intensive group

–Myocardial infaction 16% lower in intensive group

–Coronary revascularization 16% lower in intensive group

–Unstable angina 19% lower in intensive group

–And, all of the above curves were diverging over time (ie, intensive group doing increasingly better)

–No significant effect on fatal MI or new angina

So, how does one put this all together and apply it to primary care patients?

–It should be stressed that any posthoc analysis is potentially flawed by unsuspected biases

–It is pretty clear from many observational studies that there is a dose-response curve, with higher A1C associated with more heart disease. It is important to recognize that those with higher A1C may also have more comorbidities, may not take care of themselves in many different ways which may significantly adversely affects their health, etc (ie, these observational studies may have an inherent bias, thereby overstating the A1c/CAD relationship). But in this regard, it is interesting that there have been a few studies finding that even mildly elevated A1Cs, even in the prediabetic range, are associated with more heart disease. In a UK observational study for example, comparing those with A1C <5.0, men with A1C of 5.5-5.9 had a 56% increased risk of CAD events and overall mortality, those with A1C of 6-6.4 had 80% increase, and so on. fewer women had events in general, and had a similar trend with A1C but did not reach significance until A1C >7 (see Ann Intern Med. 2004;141:413-420). These studies were also observational and potentially biased, though I do treat a patient with an A1C in the high five to six range more aggressively in terms of pushing for lifestyle changes and even therapy (eg I am more likely to prescribe a statin in someone with highish A1C and otherwise marginal indications than if the A1C were lower).

–Another interesting posthoc analysis of the ACCORD trial also found that lower achieved A1C was associated with fewer cardiovascular events.  This study found that the increased mortality differences found in ACCORD between the standard and intensive groups could be explained by which group the patients were assigned to!!!  that is, although the achieved A1C did matter in terms of cardiac outcomes (lower A1C, fewer outcomes), those flogged with more meds to achieve it did less well, and those who easily achieved it did better (see Diabetes Care 2010; 33: 2722-24)​.

–So, how does one reconcile the overall study conclusion that intensive therapy in the ACCORD trial is associated with a 22% increased mortality, yet in the posthoc analysis the specific items above were better with intensive therapy? There was an interesting Italian study in 2009 (see Ann Intern Med. 2009;151:854-860) which found that for those diabetics with few medical comorbidities, those with A1C <6.5 had fewer cardiac events. in those with many comorbidities, there was no difference if A1C <6.5, or < 7.5 or higher (ie, a lower A1C did not matter). So, it is possible that the group on intensive therapy in ACCORD included 2 subgroups: one with very difficult-to-control diabetes who perhaps had worse outcomes by flogging them with more meds and one easily controlled who actually did better, but that the totals for the group was overall a poorer outcome. There might also have been a role played by rosiglitazone, which seems to cause heart disease (and, I think, be taken completely off the market). in addition, those in the intensive group with more difficult-to-treat diabetes may be  different physiologically (eg, they had more comorbidities and perhaps more systemic pathologic effects of the diabetes) or behaviorally (less adherent to meds, lifestyle, etc) than those with easier-to-treat diabetes.

–My fear is that the negative publicity about the ACCORD trial (especially in conjunction with the ADVANCE and VADT trials) has led to more complacency about pushing for lower A1C goals.  My sense is that if lower A1C’s can be achieved easily and with better drugs (especially metformin, then moving to sulfonylureas/insulin, or even pioglitazone as in the PROACTIVE study), and especially in younger/healthier individuals, then that is very likely to be good not just for preventing microvascular complications (which are pretty clearly better with lower A1C levels) but also with heart disease. and that adding on more and more medications (flogging) just to decrease the A1C may in fact be harmful. A1C is a diabetes marker, but our goal as providers is to treat patients, not markers. It seems to me that the above analysis highlights that we should be treating the whole patient, taking into account their age, comorbidities, lifestyle, etc and not just adding on more and more medicines just to get the A1C lower (though, unfortunately, measuring A1C is the low-hanging fruit that is so easy for outside organizations to rate us on).

–Of note, there is also an article in the current Evidence-Based Medicine journal by Francesco Giogino (see 10.1136/ebmed-2014-110010) finding that the increased cardiovascular mortality in the ACCORD trial was predominantly in younger and not older individuals, though the risk of hypoglycemia was higher in the older group.

Primary Care Corner with Geoffrey Modest MD: Trigger Finger Injections

18 Dec, 14 | by EBM

A study from Missouri assessed the longterm outcome of a single corticosteroid injection for a trigger finger (see J Bone Joint Surg Am 2014 Nov 19; 96:1849​). They assessed 366 patients who had a first injection and followed a minimum of 5 years.

Background:

–Trigger fingers are pretty common. lifetime risk estimated in general population of 2.6%, 4-10% in diabetics

–And, from my patients, pretty uncomfortable and affects daily functioning

Results:

–66% female, average age 59 yo, 44% with multiple trigger fingers, 24% with diabetes. majority had symptom of “catching” but able to actively extend the digit​.

–Their protocol was injecting the A1 pulley area with methylprednisolone 40mg/cc, 1cc, and lidocaine without epinephrine 1%, 0.5 to 1 cc.

–Primary outcome (which was to not get subsequent injection or surgical release) of the affected digit was in 45% of patients, with a 56% success rate in females (vs 35% in males), and approx 38% in males and females with multiple trigger fingers.

–Of the treatment failures, 64% got another injection, 33% had surgical release

–84% of treatment failures were in the first 2 years after injection (ie, those who lasted 2 years did well longterm)

–Other studies have found even higher longish term success rates (one with 92% for trigger thumbs, another with 72%)

So, a few comments:

–These are really easy injections. I use just 1/2 cc of triamcinolone 40mg/cc plus 1/2 cc of lidocaine 1% and inject with a 30 gauge short needle (though it still hurts: thick skin and too many nerves), injecting where I palpate the nodule, which is right at the A1 pulley entrance, close to the MCP joint on the volar surface). and, though I have not looked at the success rate rigorously, I am confident that in the dozens I have injected, at least  90% have had really good responses and it is pretty rare that patients come back for more. and, even if the injection lasted only 1 year, that’s a lot of relief for the patient, and re-injections (done rarely by me) have also been successful.  after 2 injections, I would suggest surgical intervention.

–The injections take about 3 minutes and are the easiest of my patient visits (a thousand times easier than the more frequent patient with uncontrolled diabetes, hypertension, depression, domestic violence…….). And, as an aside, an orthopedic surgeon doing this injection probably gets as much $$ as my health center collects for 5 visits of my more difficult patients…

Primary Care Corner with Geoffrey Modest MD: German national colonoscopy screening results

17 Dec, 14 | by EBM

By: Dr. Geoffrey Modest

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 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 screening colonoscopies)

–CRC overdiagnosis: 4500 (1 in 1089 screening colonoscopies)

–97% of all CRCs prevented and 89% of those detected earlier by screening were in people up to 75 yo; 28% of overdiagnoses were in those >75 yo

–Probabilities of CRC prevention are highest in colonoscopies conducted around age 60 (5% among men and 3.5% among women), and lowest at age 80 (2% for men and women)

–Probabilities of early detection increase with age up to about 2% by age 80

–Probabilities of overdetection increase with age: <0.1% at age 65 to <1% by age 80 in both men and women

So, pretty impressive findings. a few caveats:

–We still do not have a real randomized controlled trial showing that colonoscopy is effective in reducing mortality (though RCTs do exist for fecal occult blood testing and sigmoidoscopies), though screening colonoscopies have been accepted as the gold standard in many places (including Boston)

–In terms of overdiagnosis, they state it is defined as “cancers detected as screening colonoscopy that would not have become clinically manifest during lifetime without screening”. unclear exactly where they get their data or its quality

–Transitions from adenoma to cancer were derived by mathematical modeling from previous trials, with presumed annual transition rates approx as follows.

–Nonadvanced adenoma to advanced: men approx 4.0%, women approx 3.7% with nonsignificant change by age

–Advanced adenoma to preclinical cancer: men 2.6% age 55-59, increasing to 5.2% if over 75yo; women 2.5% age 55-59, increasing to 5.6% if over 75yo​

–Preclinical cancer to clinical cancer: men approx 19%; women approx 20% with no clear age trend

–Their conclusion is that screening between age 55-70 is the most effective in eliminating CRC risk (I would add that from older data I’ve seen, there is an increased risk of screening people >75 yo, with decreased ability to do good colonoscopy because of higher likelihood of poor prep and increased likelihood of perforation)

–They comment that the risk of overdiagnosis in CRC is much less than that found for screening mammography (19%). For PSA screening, they cite overdiagnosis of prostate cancer to be 2.3-3.3%.

–Bottom line: this study confirms and reinforces others that colorectal cancer screening is one of the most important screening tests we do. I should note that the age range suggested in the US is pretty variable depending on recommending agency. For those at average risk, for example, the USPSTF recommends any of 3 approaches, including colonoscopy every 10 years, from age 50-75. the Am College of Gastroenterology mostly agrees but suggests starting at age 45 in African-Americans, the Am Cancer Society/Multi-Society Task Force suggest starting at age 50 but continuing until the life-expectancy is <10 years. [As a perspective here, an 85 year old woman in excellent health has about a 10-year life expectancy.] Another issue with our not having a uniform and coherent health care system….

Primary Care Corner with Geoffrey Modest MD: Pneumococcal vaccine in kids helps kids and adults

17 Dec, 14 | by EBM

By: Dr. Geoffrey Modest 

NEJM had an article from South Africa looking at the efficacy of the pneumococcal conjugate vaccine from 2005-2012 (initially PCV-7, then PCV-13 as of 2011) in kids and adults (see DOI: 10.1056/NEJMoa1401914​). They identified 35,192 cases of invasive pneumococcal disease (IPD) and assessed incidence before the vaccine (baseline), with after. Results:

–In children <2 yo, rate of IPD declined from 54.8 to 17.0 cases/100,000 person-years overall, and from 32.1 to 3.4 of the PCV-7 covered serotypes, translating to a 69% decrease in all serotypes, 89% decrease in PCV-7 covered serotypes, but a nonsignificant increase of 6% in nonvaccine serotypes (from 186 to 205/100,000 person-years)

–In children not infected with HIV, IPD decreased in the specific PCV-7 serotypes by 85%, though disease caused by noncovered strains increased 33% (though the absolute numbers were very low: 1/5 of the IPD cases).  In those infected with HIV, the incidence of IPD is 25x higher, the efficacy of vaccine pretty similar, and there was no increase in noncovered strains

–By 2012, the incidence of IPD from the PCV-13 serotypes not included in the PCV-7 vaccine declined 57% in children

–In those younger than 10 weeks old, IPD decreased 36%, nonsignificant increase of 2% in nonvaccine serotypes

— In older kids, vaccine still effective: age 2-4 yo — 60% decrease in all serotypes; age 5-9yo, 44% decrease; age 10-14yo, nonsignificant decrease of 6%, though the incidence was very low; 15-24 yo: 30% decrease

–In adults aged 25-44, rate of IPD declined from 11.9 to 7.9 cases/100,000 person-years overall, and from 3.7 to 1.6 of the PCV-7 covered serotypes, translating to a 34% decrease in all serotypes, 57% decrease in PCV-7 covered serotypes, but a nonsignificant decrease of 11% in nonvaccine serotypes (from 559 to 555/100,000 person-years). Small difference in 45-64 yo at 14% decrease; no difference in those >64yo

–Also, of note, the rate of IPD in children <2yo caused by penicillin-nonsusceptible strains declined by 82% and by penicillin-susceptible strains by 47%. and multi-drug resistant strains by 84% and non-multi-drug resistant strains by 38%

So, a few issues.

–As background, South Africa has a remarkably high incidence and mortality from IPD in kids (and adults). And, they have an exceptionally high rate of antibiotic resistance to IPD (and most of the resistant strains are included in PCV-7). This antibiotic resistance was highlighted in MMWR a couple of decades ago, also noting increased incidence of pneumonia overall there (which, as I remember, was attributed to men working in coal mines, breathing dust which could affect local lung immunity mechanisms, as well as crowded conditions). There was significant concern for the spread of multi-drug resistant strep pneumonia, both within and outside of South Africa.

–In this study above, they gave kids PCV-7 at ages 6 and 14 weeks of age with a booster at 9 months (different from US recommendations: primary series age 2, mo, 4 mo, 6 mo, followed by booster 12-15 months old). Not sure how much this would affect results.

–They confirmed a remarkable reduction in vaccine-associated serotypes and in general major decreases in IPD in South Africa, as noted above.

 

–PCV-13 vaccination is one of most important vaccines we give. It is highly immunogenic and has dramatically decreased IPD in kids in the US, as is evident even in our health center (i cannot recall any admissions for pneumococcal meningitis since the introduction of PCV-7, with several cases — some fatal — previously).

–One issue with vaccines in general and IPD in particular, is that we conceivably could be selecting for much more lethal non-covered strains (new strains of strep pneumo colonize the nasopharynx on a regular basis, and at an increased rate in South Africa). And the good news so far is that this does not seem to be the case (ie, no significant increase in noncovered serotype infections, and most pointedly — no increase in highly virulent strains), and, to boot, it is reassuring that PCV-13 seems to confer increased protection against antibiotic-resistant strains.

–And this study confirms that immunizing kids helps adults (especially young adults who likely have the most exposure to those precious, but disease-ridden kids…)

Primary Care Corner with Geoffrey Modest MD: CDC recs on HIV prevention in adults and adolescents

17 Dec, 14 | by EBM

By: Dr. Geoffrey Modest

HIV_CDCThere was a recent update of the CDC’s “recommendations for HIV prevention with adults and adolescents with HIV in the United States” — see here and you too can download the 240 page document…). The overall focus of this update is to develop systems of care/infrastructure to facilitate improved access to and retention in care of HIV-positive patients. The underlying issue is that recent studies have found that the vast majority of people with HIV are aware of their disease (around 85%, thanks to much more aggressive screening programs and, it seems to me, a broader acceptance of HIV in many communities), but only 2/3 are linked to care, 40% are retained in care, 1/3 prescribed antiretrovirals, and only 25% were effectively treated to suppress their HIV viral load (which has the dual benefit of, first, turning HIV infection from pretty much a death sentence into a chronic disease, and, second, vastly reducing transmissability to others — ie treatment as prevention). This update ​does not cover clinical care of HIV or related infections. Basic issues it covers are:

–Barriers to care and medication adherence, including getting people into care and retention in care.

–Developing systems to provide integrated medical and social services to support HIV-infected individuals

–Systems to implement a widespread HIV outreach, testing and treatment program, including the creation of collaborative teams of clinical and nonclinical providers. there is a general focus in the paper for shared decision-making, communicating in a respectful and culturally-appropriate manner, and developing community-based resources

–Risk screening and reduction interventions for HIV and sexually-transmitted diseases

–HIV partner services, including PrEP (preexposure prophyllaxis) and nPEP (nonoccupational postexposure prophylaxis) to prevent transmission to noninfected partners, in collaboration with local health departments

–HIV prevention, testing, and procedures related to pregnancy

–Quality improvement and program monitoring, focusing on improving the delivery and quality of care, with ongoing monitoring (as with all of the above, the recommendations are replete with references)

We are certainly fortunate in Massachusetts that the Dept of Public Health is very supportive of community initiatives, working with us to provide team-based care, focusing on case management (for nursing and social services) and enrolling people into special insurance programs through which they get free medications.

Primary Care Corner with Geoffrey Modest MD: E-cigarettes, again

15 Dec, 14 | by EBM

By: Dr. Geoffrey Modest

And another issue comes up with e-cigarette. Front page story in the New York Times on health hazards from contaminated e-cigarettes made in China. 90% of the world’s e-cigarettes are currently made in China, with expectations to export >300 million to the US and Europe this year. Although a New York Times review in Shenzhen found that many large factories were legitimate and did make efforts at quality control, there is no consistent regulation and some had no testing equipment. And some e-cigs are literally made in a garage and are knock-offs of established brands.  The result is that some fake e-cigarettes, which may even be mixed in with legitimate ones, may have hazardous metals from their inappropriate manufacturing process, with 25 or so different elements, including large amounts of nickel and chromium, as well as tin particles, lead, zinc and carcinogens, and even diethylene glycol (used in antifreeze). When e-cigs first were developed, there were no regulations. The US has just begun to develop specific regulations for manufacturers, though this could take years.

So, adds to the concerns of e-cigarettes.

Primary Care Corner with Geoffrey Modest MD: Chronic fatigue syndrome

12 Dec, 14 | by EBM

By: Dr. Geoffrey Modest 

The AHRQ (Agency for Healthcare Research and Quality) came out with an evidence report/technology assessment for the diagnosis and treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome — ME/CFS (see here), reviewing 71 studies in 81 publications.

Findings:

–In general, this diagnosis is entertained when there is chronic and disabling fatigue, along with a variety of other symptoms including neurological and cognitive changes, motor impairment, pain, sleep disturbance and altered immune and autonomic responses. The etiology is unknown: it is unclear whether ME and CFS are part of the same illness, or whether this is just a nonspecific set of symptoms shared by other disease entities. The diagnosis of ME/CFS requires exclusion of other possible diagnoses (e.g., rheumatoid arthritis or other immune diseases, etc) and there is considerable overlap with some psych diagnoses (about 2/3 of cases, though hard to tell if these are primary or secondary psych issues — i.e. do they cause the fatigue and other symptoms or result from it). There are 8 different case definitions of ME/CFS, with those just for ME requiring postexertional malaise and having the more symptomatic subset. In this technology assessment they were not able to determine differences in accuracy between these definitions nor a universally accepted reference standard.

–Self-reported symptom scales differentiate ME/CFS from controls, but they are not adequately evaluated to determine validity or generalizability to large populations

–The diagnosis itself has some “harms”: patients may feel stigmatized in terms of financial stability, work opportunities, judgment by others, social isolation (found in several studies), or in misdiagnosis and not having the real issue treated (e.g., depression)

–35 treatment trials, with no medications approved by the FDA for this condition.

–Rintatolimod, an experimental immunomodulator not approved by the FDA, improved exercise performance vs placebo (small studies, low strength of evidence)

​–Other meds were inconclusive (galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, acyclovir). These meds were targeting different potential etiologies: immune dysfunction, viral causes, depression. Insufficient evidence also for rituximab (1 trial, 27 patients, with improved physical health and function, but not other outcomes)

–Complementary and alternative medicine. 7 trials. inconclusive results, though “studies of homeopathy, pollen extracts, and L-carnitine preparations reported benefit for some outcomes”, but small sample sizes, methodologic issues with studies, and no reports of adverse effects

–Counseling and GET (graded exercise treatment) improved function, fatigue and quality of life, with GET having more harms and withdrawal rates than counseling therapies or controls. Counseling improved fatigue (7 of 11 trials), functioning (4 of 11 trials), quality of life (2 of 4 trials) and global improvement (2 of 2 trials).

So, a pretty mixed bag. Uncertainty about diagnosis/case definition (which makes it difficult to conduct effective trials, and, to me, makes it pretty likely that ME/CFS is a hodge-podge of different entities), and it seems that the best treatment is counseling. But a couple of other issues. There may well be a relationship with higher socio-economic status, as found in several studies, and my experience in an inner city health center is that in the past 30 years I have seen approximately 1 person who fit the broad scope of this diagnosis, though I must admit there could have been some ascertainment bias on my part…. also, it is potentially very harmful to give this diagnosis incorrectly and not address the real cause of the fatigue. in the workup of the patient, most of the medical causes have been assessed (though it is certainly possible that some as-of-yet unidentified virus causes a lot of the problems), but my concern is that us medical providers may miss/not treat significant psych issues and thereby do the patient a real disservice ​(e.g., whether the depression or sleep disorder is primary or secondary, it should be treated).

Primary Care Corner with Geoffrey Modest MD: Herbal/dietary supplements and liver injury

12 Dec, 14 | by EBM

By: Dr. Geoffrey Modest

There was a rather disturbing article in the journal Hepatology showing increasing hepatoxicity from herbals and dietary supplements (HDS) (see DOI: 10.1002/hep.27317). The report is from the Drug-Induced Livery Injury Network (DILIN, supported by National Institute of Diabetes and Digestive and Kidney Diseases), reporting on the findings in 8 US referral centers (including centers in California, Connecticut, Indiana, Michigan, Minnesota, North Carolina, Pennsylvania, taxes), assessing consecutive patients from 2004-2013 with hepatoxocity from either medications or HDS, a total of 839 patients. attribution of cause of hepatotoxicity was from expert opinion, including biochemical evidence of hepatic injury with assessment for viral or autoimmune hepatitis, checking serum ceruloplasmin, iron studies, and a-1 antitrypsin, and reviewing biopsy if available.

OLYMPUS DIGITAL CAMERAFindings:

–130 patients (15.5%) with liver injury from HDS, 709 from medications

–The incidence of HDS hepatotoxicity increased from 7% to 20% over the 10-year observation period

–Of the HDS cases, 45 were from bodybuilding HDS and 85 from non-bodybuilding

–Bodybuilding HDS cases were exclusively in men (median age 31) and were milder: prolonged jaundice (median 91 days), but no fatalities or liver transplants.

–Non-bodybuilding HDS cases mostly in middle-aged women (median age 47, 65% women), and more frequently led to death or liver transplantation as compared to medication-induced hepatotoxicity (13% vs 3%)

So, this seems to be a very real problem, even though this is not a rigorous population-based study. more than 1/2 the US population consumes HDS. Although overall the consumption is highest in non-Hispanic white women >40yo and with higher levels of education, my experience is that use of these supplements is very common in our multicultural poor inner-city community. I see a lot of young men taking testosterone and other body-building HDS, and many people who buy TV-advertised (and quite expensive) supplements (ie, I don’t think this is only a white middle-class issue).  There are even data that taking multivitamins are not helpful in general population. The Physicians Health Study II of 14,641 men >50yo and followed 11.2 years found no benefit of multivitamins on major cardiovascular events or total mortality, even if they had baseline history of coronary artery disease (see JAMA. 2012;308(17):1751-1760) and another study of 1700 people, 82% men, taking multivitamins after an MI and followed 55 months similarly found no benefit (see Ann Intern Med. 2013;159:797-804)  all of this confirms the oft-repeated concept (by me, at least) that we should be eating well and exercising, not looking to micro- or macro-nutrient additions to improve health (ie, there is no easy fix….).

Primary Care Corner with Geoffrey Modest MD: Longish-term followup of bariatric surgery

11 Dec, 14 | by EBM

By: Dr. Geoffrey Modest 

JAMA published a systematic review in September of the long-term followup after bariatric surgery (see doi:10.1001/jama.2014.10706). Of all the studies, they found 29 which had clinical outcomes (type 2 diabetes, hypertension, hyperlipidemia), with at least 2 years of followup. 10 were RCTs. Longest follow-up was (only) 5 years. Results:

–Weight loss (> 50% of excess wt loss): in 31% of gastric band studies and 65.7% with gastric bypass, with mean % excess wt loss for gastric bypass = 65.7% (n=3544) and for gastric band = 45% (n=4109). 26 studies included

–Diabetes (achieving Hgb A1C < 6.5% without meds): gastric bypass = 66.7% (n=428) vs gastric band = 28.6% (n=96). six studies. mean decrease in A1c was 2.2% after gastric bypass and 1.5% after gastric band

–Hypertension (achieving BP<140/90 without meds): gastric bypass = 38.2% (N=808) vs gastric band =17.4% (n=247). 3 studies. 

–Hyperlipidemia (achieving chol<200, HDL>40, LDL <160 and TG <200): gastric bypass = 60.4% (n=477) vs gastric band = 22.7% (n=97). 3 studies. (none of the studies, however, reported use of lipid-lowering agents….)

–Insufficient data on gastric sleeve resections for long-term outcomes

–Complications: gastric bypass vs gastric band: death in 1% vs 0.2%

For gastric bypass:

–Incisional hernia, internal hernia, marginal ulcer in 1% each

–Anemia, Fe deficiency requiring transfusion or vit B12 deficiency in 2% each

–Re-operation for abdominal pain or nonhealing ulcer in 0.1% each

For gastric band:

–Port leak/revision 6%

–Band slip/obstruction 5%

–Treatment failure requiring revision 3%; band removal 2%

​–Erosion, esophagitis 1% each

So, the issues here are that obesity is a chronic disease, with likely benefit of identifying early and helping people from developing more severe obesity and its complications (and stressing the importance of public health initiatives to improve access to good/cheap food, exercise/safe neighborhoods, and generally promoting a more healthy lifestyle/curtailing the promotion of fast foods/junk foods, etc — FYI, there was a recent editorial promoting a tax on fast foods/junk foods to subsidize the rather expensive cost of fresh veges/fruits, for example). Bariatric surgery definitely has a place in the treatment of severe obesity (though I have seen some really dramatic results in some patients given the appropriate supports​, losing as much as with surgery). But one of the issues of bariatric surgery is that over time, people tend to gain weight, with one 8-year study finding treatment failure in 42% (which was probably closer to 50% with more intensive efforts to find those who dropped out of the study). in this context, it seems that in the longish term results here (limited by the max of 5 years noted), gastric bypass seems to get the best results (there are too few data on the gastric sleeve operations to comment).

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