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Primary Care Corner with Geoffrey Modest MD: Colonoscopy Screening in the Elderly?

10 Nov, 16 | by EBM

By Dr. Geoffrey Modest

A recent observational study of Medicare recipients found that those 70-79 years old seemed to benefit from colorectal carcinoma (CRC) screening (see doi:10.7326/M16-0758). Study sponsored by the NIH.

Details

  • 1,355,692 Medicare beneficiaries (from 2004-2012) aged 70-79, who were of average CRC risk, assessing 8-year risk for CRC and 30-day risk for adverse events.
  • Average risk was defined as: no history of adenoma, IBD, colectomy, and no colonoscopy/sigmoidoscopy/fecal occult blood in the past 5 years; and no prior abdominal CT, diagnosis of anemia, GI bleed, other GI symptoms, weight loss within the past 6 months
  • Included were those who were “health-conscious”, defined as having received at least 2 of the 3 preventive annual Medicare serviced of annual wellness visit, influenza vaccine, and breast or prostate cancer screening

Results:

  • 70-74yo, 8-yr risk of CRC was 2.19% (2.00 to 2.37%) in the screening group vs 2.62% (2.56 to 2.67%), so absolute difference of -0.42% (-0.24% to -0.63%)
  • 75-79yo, 8-yr risk of CRC was 2.84% (2.54 to 3.13%) in the screening group vs 2.97% (2.92 to 3.03%), so absolute difference of -0.14% (-0.41% to +0.16%) – i.e. nonsignificant
  • 70-74yo, excess 30-d risk of adverse events with colonoscopy was 5.6 events per 1000 people (4.4 to 6.8)
  • 75-79yo, excess 30-d risk of adverse events with colonoscopy was 10.3 events per 1000 people (8.6 to 11.1)

Commentary:

  • The current guidelines, as in many guidelines, varies by who is writing them. The USPSTF currently recommends screening by any of several methods, from 50-75 yo in those at average risk (evidence grade “A”, with individualized decisions in those 76-84, though the evidence grade here was “C”, meaning that they recommend”offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small”
  • There are several concerns about drawing major conclusions from this new NIH-sponsored study:
    • Although there are 132,000 new cases of CRC in the US per year and 50,000 CRC-related deaths, it is not clear to me that this proportion applies in the more elderly population. As noted in this study of “health conscious” elderly, there was much more morbidity found in the older 75-79 yo cohort (e.g. hypertension in 80.5% vs 74.9% in the 70-74 yo, ischemic heart disease in 45.3% vs 36.6%). This increased morbidity is likely to translate to more people “dying with the cancer than dying from the cancer”.
    • All of this data is from the Medicare database, which, my guess, does not have the most accurate detailed information, and does not even have the CRC-specific mortality, a pretty useful endpoint for this study…
    • I am not so sure of the assumption that people who are more “health conscious”, as they define it, are in fact healthier/qualify as “average risk”. My guess is that the threshold for colonoscopy screening in the elderly varies lots by who the provider is (some may well push continued screening either in the undocumented belief they are helping the patient, they are uncomfortable effectively saying “you are too old to continue screening”, etc.), and some patients I see request different screens even with considerable morbidity (either they do not want to deal realistically with death/their prognosis, they are pretty somatic and want to  search for problems, etc). And, I would not be surprised if a higher percentage of less healthy patients get flu shots more aggressively (one of their “health conscious” criteria), either because of provider or patient preferences (and the fact that they come in for health care more often, with more opportunities for vaccines). Only a well-designed prospective trial would work to sort this out.
    • This study was limited to colonoscopy screening, which has been documented in the past to work much less well in the elderly, with higher numbers of inadequate preps (leading to more colonoscopies with more intensive preps), and (also perhaps related) higher perforation rates, which can lead to major abdominal surgery in an older and higher risk population. So, perhaps not the screening method of choice…
    • The stage-shift found in screening (i.e., fewer cases of more advanced CRC lesions in the screened group) certainly is supportive of screening, but again, colonoscopy is not only very expensive but quite invasive, so it really is important to look at real clinical outcomes before making a screening decision (i.e., does this stage-shift to higher stage lesions really translate to more morbidity/mortality?)
  • It seems to me to be a tad disingenuous to conclude in the abstract that “screening colonoscopy may have had a modest benefit in preventing CRC in beneficiaries aged 70 to 74 years and a smaller benefit in older beneficiaries”, but then in the last paragraph, having basically the same sentence, but with the qualification “and a smaller (if any) benefit in those who are older” (my emphasis). The reality is that many busy clinicians rely on the accuracy of the abstract and may not read the whole article, especially in primary care practice which is not only really busy, but requires clinicians to read and assimilate literature from all of the specialties. The above article also tends to minimize the adverse effects, stating they were “low but greater among older persons”. But, the rate was twice as high, and I would not be surprised if the actual effect of these adverse outcomes, in terms of resulting functional impairments, increases in an older population (they just don’t bounce back as well even from less-than-severe adverse effects).
  • And, this is really my main criticism of the take-home message of this study: I would phrase the conclusion more like “there is no clear evidence that screening colonoscopy offers any significant benefit in those 75-79 years old, that the possible benefit in terms of decreasing CRC diagnosis may translate even less into real morbidity and mortality benefit in this age group, and that there was almost a doubling of adverse events in this pretty susceptible population.” I personally do think that a healthy 79 yo, who really does have a realistic life expectancy (e.g., the healthiest 25% of women aged 80 has a 17 year life expectancy, and men 13 years), might realize actual clinical benefit by diagnosing and treating CRC early, especially since treatment for early lesions is pretty benign, but I have adopted FIT testing as my preferred non-invasive CRC testing, which should help winnow the colonoscopies and their adverse effects to a much smaller exposed group, and one with a higher yield for benefit over risks.

Primary Care Corner with Geoffrey Modest MD: Continue Aspirin After Lower GI Bleeds?

17 Jun, 16 | by EBM

By Dr. Geoffrey Modest

A rather common clinical conundrum in patients with/at high risk for cardiovascular disease is whether to reinstate aspirin after a GI bleed. A recent retrospective study from Hong Kong suggested that the benefit outweighs the risk for lower GI bleeds (see doi.10.1053/j.gastro.2016.04.013). They reviewed their data on patients with documented lower GI bleed (melena or hematochezia and absence of upper GI source) from 2001-2008.

Details:

  • 295 patients who were on aspirin at the time of the lower GI bleed, followed up to 5 years
  • 93% were considered to be of “high cardiovascular risk”, using the Antithrombotic Trialists’ Collaborative definition: history of unstable angina, acute MI, prior MI, stroke, or TIA
  • Non-users were defined as taking aspirin <20% of the follow-up period (n=121; 87% actually took aspirin <10% of the follow-up period); users were those with cumulative use >50% of that period (n=174; 84% took aspirin >75% of the follow-up period). Aspirin use was determined by prescription patterns.
  • All used <=160mg aspirin, and 88% used only 80 mg/d
  • Non-users were older (76.7 vs 73.1 years, p=0.003), fewer smokers (26.4% vs 42.0%, p=0.006), and more needed transfusion of >= 2 units (54.5% vs 39.7%)
  • Predefined covariables at baseline: age, sex, alcohol consumption, smoking, severity of comorbidities, history of GI bleeding (upper and lower), blood transfusion, meds (anticoagulants, steroids, non-aspirin antiplatelet drugs) within the 30 days prior to index bleed.
  • Outcomes assessed: recurrent lower GI bleed, serious cardiovascular events (nonfatal MI, nonfatal stroke, death from vascular cause), and deaths from other causes
  • Results, comparing non-users to users:
    • Lower GI bleeding recurred in 18.9% of those on aspirin vs 6.9% of non-users (SHR 2.76; p=0.011) [SHR is subdistribution hazard ratios, which from my understanding is the probability of an event due to aspirin at a moment in time, comparing cause-specific cumulative incidences of different effects]
      • Overt bleeding in 6.6% of non-users (n=8) vs 17.8% of users (n=31). both groups were transfused a median of 2 units of blood
      • Occult bleeding in 1.7% (n=2) of non-users vs 6.9% of users (n=12)
    • Serious cardiovascular events occurred in 22.8% of those on aspirin vs 36.5% of non-users (SHR 0.59; p=0.019)
    • 2% of aspirin users died from other causes vs 26.7% of non-users (SHR 0.33; p=0.001): 42 patients overall died, including 22 from sepsis, 10 from cancer, and 6 from renal failure
    • Multivariable analysis: aspirin use was an independent predictor of rebleeding but protected  against major cardiovascular events and deaths

Commentary:

  • A large number of people are on aspirin, up to 50% of men >40 yo. The major GI toxicity is upper GI, which can be decreased by concomitant use of a proton pump inhibitor (though that has its concerns: see http://blogs.bmj.com/ebm/2016/02/25/primary-care-corner-with-geoffrey-modest-md-ppi-use-and-dementia/ which comments on a couple of articles on potential PPI-associated dementia and includes references to PPI-associated microbiome changes, MIs in those without prior history of heart disease, chronic kidney disease, pneumonia and a variety of GI infections, decreased bone density, etc.). But there is somewhat more concern about the lower GI bleeding: several observational studies have documented an increase in aspirin-associated lower GI bleeding (where PPIs are unlikely to be protective, so continued aspirin use is more dangerous). And those hospitalized for lower GI bleeding actually have a higher mortality than those with upper GI bleed.
  • It is hard to draw clear conclusions from a retrospective study, given that the nonusers were older (which perhaps explains their increase in noncardiovascular deaths), though fewer were smokers. So, the multivariate analysis may have not fully compensated for differences in all risk factors/biases.
  • But, I would add a few points:
    • This article highlights the very likely conclusion that those with a lower GI bleed but at high cardiovascular risk are more likely to get benefit over harm by continuing aspirin use. The issue with the more common adverse event of aspirin-associated upper GI bleeding is a bit easier given the potential of adding acid suppression therapy to minimize recurrent risk
    • I think it is also important to stress that aspirin may have real benefits in preventing cancer (see below). The data on this has been accumulating for many decades (I remember seeing data on aspirin or NSAIDs decreasing colonic adenomas/cancer dates back to the 1970s, with the support of a really large number of suggestive epidemiologic and animal studies), though potential cancer prevention was only recently incorporated into mainstream recommendations (see USPSTF guideline link below).

http://blogs.bmj.com/ebm/2015/09/09/primary-care-corner-with-geoffrey-modest-md-low-dose-aspirin-and-colon-cancer-risk/ looks at the data on colon cancer prevention by low dose aspirin with links to other blogs on ovarian, prostate and other cancers.

http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer?ds=1&s=aspirin is a link to the USPSTF 2016 aspirin recommendations, which highlights using low dose aspirin in the primary prevention of both cardiovascular disease and colorectal cancer (i.e., not just for cardiovascular protection)

Primary Care Corner with Geoffrey Modest MD: Colorectal Screening Guidelines From Canada

4 Mar, 16 | by EBM

By Dr. Geoffrey Modest

The Canadian Task Force on Preventive Health just published a provocative guideline on colorectal cancer (CRC) screening in those not at high risk (see DOI:10.1503 /cmaj.151125).

Details:

Background:

  • ​CRC is the 2nd most common cause of cancer-related death, with lifetime probability of 3.5% in men and 3.1% in women
  • The incidence and mortality in both men and women increases dramatically in the 70-79 year age groups and continues to increase in the >80 year olds

Recommendations:

  • Adults aged 50-74:
    • Screen those aged 50-59 using gFOBT or FIT (guaiac fecal occult blood test, or fecal immunochemical testing) every 2 years or flexible sigmoidoscopy every 10 years — weak recommendation: moderate-quality evidence
    • Screen those 60-74 as with 50-59, but strong recommendation: moderate-quality evidence
    • Do not screen adults >75yo– weak recommendation: low-quality evidence
  • Rationale for recommendations:
    • Meta-analysis of screening studies:
      • Guaiacs (in those 45-80yo): 18% reduced CRC mortality [RR = 0.82 (0.73-0.92), with absolute reduction AR = 2.7 per 1000 screened, and number-needed-to-screen NNS= 377 over 18.2 years], as well as incidence of late stage CRC [RR = 0.92 (0.85-0.99)]
      • Sigmoidoscopy (in those aged 55-74): 26% reduced CRC mortality [RR = 0.74 (0.67-0.82), with AR = 1.2 per 1000 screened, and NNS = 850 but over 11.3 years], as well as  incidence of late stage CRC [RR = 0.73 (0.66-0.82)]
      • No diff in all-cause mortality
      • ​In terms of age: studies found no reduction in mortality in those <60yo, but significant reduction in those 60-69 for guaiacs; mortality reduction in those 65-74 with sigmoidoscopy. All studies underpowered in the <60 and >70 yo Which is why there was a weaker recommendation for those 50-60.
      • A systematic review compared guaiacs with FIT and found: FIT had greater sensitivity and higher rates of detection for CRC and advanced adenomas, and also had greater participation rates than guaiac cards. The actual positive predictive value of FIT depends on the cut-off used for positivity. (The current USPSTF draft update also prefers FIT testing over guaiacs, and is proposing flex sig screening every 10 years with annual FIT but not guaiac testing — see http://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement38/colorectal-cancer-screening2 )
      • The Canadian Task Force recommends FIT/guaiac screening every 2 years to decrease the burden to patients, in light of lacking data that yearly is better (though annual was better in a study of those >70yo)
      • Flex sig screening was increased to 10 yrs based on finding that flex sig screening decreased CRC mortality and incidence until at least 11 years of follow-up.
      • Harms of flex sig were rare (0.001% with perforations, 0.05% minor bleeding, 0.009% for major bleeding and 0.015% for death)
      • Harms of screening colonoscopy were much higher (0.05% with perforations, 0.08% minor bleeding, 0.1% for major bleeding and 0.002% for death)
    • Adults >=75 yo:
      • Not screen (weak recommendation; low quality evidence, mostly perhaps because the studies were underpowered). Though they do comment that those >74 “who do not have illnesses that affect their quality of life and/or their life-span” might consider CRC screening and should discuss with clinician
    • Do not use colonoscopy for screening (weak recommendation, low quality of evidence)
      • No data looking at benefit of colonoscopy over FIT or other screening tests
      • More intensive (need more highly trained personnel), more costly. And they therefore hold colonoscopy to a higher standard in terms of lack of direct evidence of superiority of colonoscopy screening
    • Do not use other screening tests (CT colonography, barium enema, digital rectal exam, serologic tests, fecal DNA), since no RCT evidence for them. A recent study on multitarget stool DNA testing was very sensitive (better than FIT), but lots of false-positives

These recommendations differ significantly from those of the US Preventive Services Task Force of grade A recommendation to screen 50-75 yo, grade C for 76-80 yo; with guaiac or FIT every year, flex sig every 10 yrs with FIT every year, or colonoscopy every 10 years. — Though as noted above there will be new recommendations in 2016.

So, a couple of points:

  • They do not recommend screening for CRC in those >75. In a reasonably healthy 75-80 yo, both the incidence and mortality from CRC continues to increase dramatically, life expectancy overall as per prior blogs is increasing (though much more so in the US for those of higher income, and much less of an income-related difference in Canada — see http://blogs.bmj.com/ebm/2016/02/24/primary-care-corner-with-geoffrey-modest-md-increasing-disparities-in-life-expectancy/​ ). And by minimizing colonoscopy as a screening test, its attendant harms in those over 75 are mitigated (g., harder to get good prep, less adequate exam, and increased risk of severe complications such as perforation — see http://blogs.bmj.com/ebm/2015/04/10/primary-care-corner-with-geoffrey-modest-md-risks-of-colonoscopy-in-older-people/ ). So, my bar for continued screening with non-colonoscopy methods is much lower than with colonoscopy and probably should be considered more often in healthy older people.
  • I think these guidelines could be a game-changer. The new draft USPSTF still lists colonoscopy screening as recommended, though also on the list are: guaiac/FIT annually, flex sig every 10 years with FIT annually, and colonoscopy every 10 years (still much more intense than the Canadian ones, with the questionable options of plain guaiacs every year, but sigmoidoscopy every 10 years with FIT every year!!??!!). But I think there are pretty compelling arguments against colonoscopy: noneed of a really terrible bowel prep, much decreased morbidity/mortality from this more aggressive screen, less need for conscious sedation, less need for an accompanier to drive the patient home after the test, much less need for highly trained personnel (there are many sites where nurse practitioners do flex sigs outside-of-the-hospital), and much decreased cost of the other tests. One argument is that with sigmoidoscopy, one sees only ½ the colon and therefore are missing ½ of the potential cancers. But a few studies have found that colonoscopy does not affect the mortality of right sided lesions, only the left sided ones (g., see Ann Intern Med. 2009;150(1):1, a case-controlled study finding no decreased mortality by colonoscopy for right-sided lesions). Reasons?? One is that there is more microsatellite instability in right sided lesions, and these have a better prognosis. But all of this together adds to the appeal of flexible sigmoidoscopy over colonoscopy.

Primary Care Corner with Geoffrey Modest MD: Travelers diarrhea — the treatment may be worse than the disease

19 Mar, 15 | by EBM

By: Dr. Geoffrey Modest

A recent Finnish study looked at intestinal colonization by resistant bacteria in travelers to regions with suboptimal hygiene, noting that there are more than 300 million such travelers, and finding rather disturbing results (see DOI: 10.1093/cid/ciu957​). They looked specifically for colonization by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) and carbapenemase-producing Enterobacteriaceae (CPE).

Untitled3

Details:

–430 Finns were assessed before and after traveling outside Scandinavia, analyzing for the above bacteria. Participants also filled out questionnaires detailing aspects of their travel.

–mean age 40, 61% female, 45% going to Sub-Saharan Africa, 24% Southeast Asia, 14% South Asia, 9% to South/Central America or Caribbean.  15% were there for <8 days,  47% for 8-15 days, 28% for 16-30 days. 15% used antibiotics (12% for travelers diarrhea, or TD). 96% drank bottled water, 53% took probiotics, 13% neglected hand-washing, 78% consumed salads, 55% took antimalarials

Results:

–5/430 pre-travel and 93/430 post-travel stools were positive for ESBL-PE, 7 had acquired 2 different strains of ESBL-PE. None were colonized by CPE.

–by region, the risk of getting ESBL-PE was highest in South Asia (46%); then Southeast Asia, East Asia, North Africa/Middle East (33% each); then Sub-Saharan Africa (12%). No cases were found in those going to Europe, Australia, Americas

–288/430 (67%) developed TD; 75 of these 288 (26%) and 15 of those who did not develop TD (11%) became colonized with ESBL-PE. The AOR (adjusted odds ratio) for colonization with ESBL-PE was 31.0 for those who developed TD vs those who did not

–antimicrobials were taken in 66/430 (15%), in 52/66 (79% of those on antibiotics) it was for TD.  Note: they did not include doxycycline taken as an antimalarial. 79% of the antibiotics for TD were fluoroquinolones, 13% macrolides.  The AOR was 3.0 in those who took antimicrobials for TD

–although there was an increase in ESBL-PE with age, there was no increase found in travel companions or if taking antimalarials

–overall numbers for ESBL-PE:

–in those going to South Asia, 46%, with breakdown as: 23% if not develop TD or take antibiotic, 47% if developed TD but no antibiotics, 80% if developed TD and took antibiotics.

–in those going to Southeast Asia, 33%, with breakdown as: 14% if not develop TD or take antibiotic, 32% if developed TD but no antibiotics, 69% if developed TD and took antibiotics

–in those going to Sub-Saharan Africa, 33%, with breakdown as: 12% if not develop TD or take antibiotic, 8% if developed TD but no antibiotics, 28% if developed TD and took antibiotics

–1 year followup, none previously with ESBL-PE were still positive

So, a few points.

–antimicrobial resistance is surging in regions where hygiene is poor, in part by the easy access to antibiotics there, and these strains are being globalized through travelers, food and animal trade.

–antibiotic-resistant Enterobacteriaceae is becoming more of a problem in the US, with increasing reports noted by the CDC

–colonization by these resistant organisms can lead to significant infections especially in immunocompromized and hospitalized patients, so the above represents a potentially significant reservoir of resistant and potentially transmissable bad actors

–this study reinforces issues of hygiene as well as avoiding taking antibiotics for TD unless one is seriously affected (as per the guidelines. For example, see blog)

–this study also reinforces the delicate balance in the microbiome and the potentially serious problems with its disruption. I have posted several blogs on the microbiome (go to category: “microbiome” on the website), but for example, here notes the changes in the microbiome associated with non-caloric artificial sweeteners that may lead to glucose intolerance/metabolic syndrome, or the blog here details both that red meat leads to changes in the microbiome which increase the production of TMAO, a significant cardiotoxin, and that part of metformin’s hypoglycemic action at least in mice is mediated through microbiome changes.

Primary Care Corner with Geoffrey Modest MD: Stress and peptic ulcers

1 Feb, 15 | by EBM

By: Dr. Geoffrey Modest

Older studies have shown an association between stress and peptic ulcer disease. At least the ones I’ve seen have not controlled for the use of NSAIDs or the presence of H pylori. However, from newer data, 16-31% of ulcers are not associated with either of these precipitating factors. The current prospective population-based study was done in Denmark, in which the researchers collected blood samples as well as an inventory of psychological, social, behavioral and medical data in 1982-3, and reinterviewed these patients in 1987-8 and 1993-4, finding that psychological stress did indeed increase the risk of ulcers (see doi.org/10.1016/j.cgh.2014.07.052​).

Details:
–3379 adults without prior history of ulcer disease were enrolled, with subsequent data on 2809 of them in 1987-8 and 2410 in 1993-4. Pretty evenly distributed in the 30-60 year age range.
–socioeconomic status (SES) was calculated from education, occupation, employment status. Stressors included working more than 40 hours/week and an assessment if the person had economic, work, family, housing , or personal problems. Subjects also answered 22 items from the Mental Vulnerability Scale (a questionnaire used by the military to screen potential recruits), a validated scale which assesses “somatization, neuroticism, depression, and anxiety.”
–a stress index was calculated which combined the baseline Mental Vulnerability; tranquilizer use; economic, work, family, housing or personal problems; unemployment; and working >40 hours/week — with a score of 0-10.​

Results:

–43% were H pylori positive, 16% were taking NSAIDs, 56% were current smokers, 39% in the lower two SES categories
–76 people were diagnosed with an ulcer over the course of the study (documented on endoscopy/radiology exam): 39 duodenal ulcers and 30 gastric ulcers
–ulcers were significantly more common in those in the highest tertile of stress scores (3.5%) vs the lowest (1.6%), with adjusted odds ratio of 2.2 (CI 1.2-3.9, p<.01). This did not change after adjusting for IgG antibodies to H pylori, alcohol consumption, or sleep duration, with a per-point odds ratio for the stress index being 1.19 (CI 1.09-1.31, p<0.001), and a clear dose-response (the higher the stress score, the more likely to have an ulcer)
–the adjusted stress relationship was lower after controlling additionally for SES, with per-point odds ratio for the stress index being 1.17 (CI 1.07-1.29, p<0.001), and further by controlling for smoking, use of NSAIDs and lack of exercise, with per-point odds ratio for the stress index being 1.11 (CI 1.01-1.23, p=0.04).
–there was a similar risk of ulcer related to stress in those who were H pylori positive or negative, or in those both H pylori negative and not on NSAIDs.
–in multivariate analysis, stress, SES, smoking, H pylori infection, and use of NSAIDs were independent predictors of ulcers.

One big plus for this study was its timing: it predated H pylori testing (and treatment), either H2-blockers and subsequently proton-pump inhibitors were available only as prescriptions and not over-the-counter, and the study was done largely before widespread use of low-dose aspirin; all of these factors significantly decrease the confounding that would exist if the study were done now. Purported mechanisms by which stress could cause ulcers include by increases in stomach acid secretion, effects on the hypothalamic-pituitary-adrenal axis (essentially all hormones are affected by stress, many of them mediated by the stress-related cortisol elevations) which can affect healing, hormone-mediated changes in blood flow to the stomach, or cytokine-mediated impairment of mucosal defenses. Some of the stress effect is likely mediated by smoking (which in one study accounted for one-third of the ulcerogenic effect of stress), alcohol or poor sleep (though these latter 2 were not confirmed in the Danish study above). Of note, there was no synergy in the Danish study between stress and H pylori in ulcer development. To me, this is a pretty impressive study despite its being observational, given the quality of the data they collected prospectively, the fact that there is a dose-response curve with each increase in their stress scale associated with increased likelihood of ulcer disease, and their controlling for many known or likely associations for ulcers.

So, not so shocking a finding (I think most of my patients are aware of the link between stress and ulcers….). However, the National Institute of Diabetes and Kidney Diseases of the NIH in 2012 notes “peptic ulcers are not caused by stress”. So, I guess my patients were right all along…

Primary Care Corner with Geoffrey Modest MD: Travelers Diarrhea Review

8 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

JAMA had an excellent review (I think) of traveler’s diarrhea (see  JAMA. 2015;313(1):71-80​). Some of their major points for those traveling to high-risk countries:

Untitled

–eating food from street vendors certainly increases the risk, though one can get it in a 5-star hotels (esp if food served buffet-style and food exposed to warm environmental conditions)

–average duration of the diarrhea is 4-5 days, though mean duration of incapacitation is <1 day. But passage of more than 10 stools/d is pretty uncommon (reported in 3% of cases)

–long-term complications can occur: postinfectious irritable bowel syndrome (PI-IBS) can occur in 3-17%, some without prior traveler’s diarrhea, though PI-IBS tends to occur in those with more serious cases and esp in those infected with heat-labile toxin-producing enterotoxigenic e. coli

–there is a great table (their Table 2) of the regional differences in the etiology of traveler’s diarrhea.  This is important to know to make sure therapy is appropriate — eg, the incidence of campylobacter is much higher in South Asia (15-25%) and Southeast Asia (25-35%), so azithro is a better antibiotic than a fluoroquinolone, to which campylobacter is often resistant

–prevention: “boil it, cook it, peel it, or forget it”. (though nothing is 100%: many cooked foods do not reach temperature of 100C, still most are safe at 60C, but some foods don’t even reach that temperature). Avoid ice.

–bismuth subsalicylate provides modest protection (taking qid may decrease diarrhea 65%)

–rifaximin (200mg 1-2x/d) also has modest effect (approx 48% in those going to south and Southeast Asia), though unclear if effective against invasive pathogens

–prophylactic antibioltics (esp fluoroquinolones) are controversial because of developing resistance (and the poor little microbiome…), but might be used in those at very high risk of complications or those on short trips with important duties precluding time off for illness

–treatment (though depends on area of travel, as above). Includes avoiding dehydration, plus:

–mild symptoms (1-3 loose stools/d): non-antibiotic — bismuth subsalicylate 2 tabs or 1 oz liquid 4x/d,or loperamide 4mg initially, then 2mg after each unformed stool with max of 8mg/d. do not use loperamide wihtout antibiotics if T> 38.5C (or, I would add, systemic symptoms).

–for moderate to severe diarrhea, antibiotics shorten course to about 1.5 days. In areas where cipro makes sense, give 500-750mg daily for 1-3 days; in South/Southeast Asia, azithro 500mg/dx3d or 1000 mg as single dose.

–for noninvasive enteric bacteria (eg NOT assoc with fever or when shigella, campylobacter, or invasive salmonella are suspected), rifaximin 200mg tid for 3 days is not inferior to cipro.  Can add loperamide with antibiotic for prompter improvement in symptoms.

Some of the guideline articles are a bit more quantitative for the treatment approaches: divide traveler’s diarrhea into mild (1-2 loose stools/d without other symptoms), moderate (1-2 loose stools/d plus at least one symptom: nausea, vomiting, abdominal pain/cramping, fever, bloody stool), classic (>2 stools/d with at least one of those symptoms). For severe diarrhea (though not stressed in this article), I would suggest trying to get packets of oral rehydration solution which is available in pharmacies in most countries (put packet in clean drinking water), or you can make it up: add 1/2 tsp of salt, 1/2 tsp baking soda, and 4 tbsp sugar to 1 liter of clean water​

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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