Evolutionary Medicine Perspectives: Helicobacter pylori, Lactose Intolerance, and 3 Hypotheses for Functional and Inflammatory Gastrointestinal and Hepatobiliary Disorders.

Many clinicians have suboptimal knowledge of evolutionary medicine. This discipline integrates social and basic sciences, epidemiology, and clinical medicine, providing explanations, especially ultimate causes, for many conditions. Principles include genetic variation from population bottleneck and founder effects, evolutionary trade-offs, and coevolution. For example, host-microbe coevolution contributes to the inflammatory and carcinogenic variability of Helicobacter pylori. Antibiotic-resistant strains are evolving, but future therapy could target promutagenic proteins. Ancient humans practicing dairying achieved survival and reproduction advantages of postweaning lactase persistence and passed this trait to modern descendants, delegitimizing lactose intolerance as "disease" in people with lactase nonpersistence. Three evolutionary hypotheses are each relevant to multiple diseases: (i) the polyvagal hypothesis posits that prehistoric adaptation of autonomic nervous system reactions to stress is beneficial acutely but, when continued chronically, predisposes individuals to painful functional gastrointestinal disorders, in whom it may be a biomarker; (ii) the thrifty gene hypothesis proposes genetic adaptation to feast-famine cycles among Pleistocene migrants to America, which is mismatched with Indigenous Americans' current diet and physical activity, predisposing them to obesity, nonalcoholic fatty liver disease, and gallstones and their complications; and (iii) the hygiene hypothesis proposes alteration of the gut microbiome, with which humans have coevolved, in allergic and autoimmune disease pathogenesis; for example, association of microbiome-altering proton pump inhibitor use with pediatric eosinophilic esophagitis, early-life gastrointestinal infection with celiac disease, and infant antibiotic use and an economically advanced environment with inflammatory bowel disease. Evolutionary perspectives broaden physicians' understanding of disease processes, improve care, and stimulate research.

Low Rate of Cancer Detection by Colonoscopy in Asymptomatic, Average-Risk Subjects with Negative Results From Fecal Immunochemical Tests.

BACKGROUND & AIMS: Screening colonoscopies are of uncertain benefit for persons with negative results from a fecal immunochemical test (FIT). We investigated detection of CRC by colonoscopy in asymptomatic, average-risk, FIT-negative subjects. METHODS: We conducted a retrospective, population-based cohort study of 96,804 subjects with an initial negative result from a FIT at ages 50-75 years, from 2008 through 2014, who then underwent colonoscopy, using the Kaiser Permanente California databases. We identified participants diagnosed with CRC from January 1, 2008 through December 31, 2015 from a cancer registry. Subjects were followed until initial colonoscopy, health plan disenrollment, death, or December 31, 2015. We reviewed records from 400 randomly selected persons without CRC (controls) for risk features to estimate the proportion who underwent screening colonoscopy. We performed logistic regression to identify variables associated with CRC detection. RESULTS: Of 257 subjects with a diagnosis of CRC, 102 did not have a record of CRC risk factors; 86 of these patients (84.3%) had non-advanced-stage CRC (no regional node spread/distant metastases). Of the 400 controls, 299 (74.75%; 95% CI, 70.49%-79.01%) lacked CRC risk features, enabling estimation that 72,263 (mean age, 57.5 ± 7.0 y; 54.5% female) had undergone screening colonoscopy. CRC was detected in 1.4 per 1000 persons after 1 FIT, without association with increasing FITs (P = .97). CRC was detected in 1.3 per 1000 persons in 2 y or less after the last FIT and in 4.4 per 1000 persons more than 2 y after the last FIT (P < .001). When the last FIT was 2 y earlier or less, CRC increased from 0.7 per 1000 persons age 50-59 y to 3.1 per 1000 persons older than 70 y. Age and time from the last FIT were associated with CRC, with adjusted odds ratios of 1.08 (95% CI, 1.05-1.11) and 2.76 (95% CI, 1.28-5.95), respectively. CONCLUSIONS: In asymptomatic, average-risk persons with a negative result from a FIT, CRC is infrequent within 2 y after the last FIT (especially for persons younger than 60 y), usually non-advanced, and unrelated to the number of FITs performed.

Internists' Misconceptions About PPIs: Increasing Knowledge and Implementing Guidelines.

Misconceptions about proton-pump inhibitor (PPI) adverse effects were common among internists, and many had changed prescribing. Among 4 scenarios representing a risk spectrum for upper gastrointestinal bleeding, 86% of physicians properly chose discontinuing PPI for a minimum-risk patient with previous gastroesophageal reflux disease, but 79% inappropriately chose discontinuing PPI for a high-risk patient with a peptic ulcer history taking low-dose aspirin. Physician self-assessment is often inaccurate. Time barriers to learning and unanswered clinical questions, especially drug issues, are common. Unscientific information can influence both physicians and patients. Strategies for increasing the guideline implementation include making scientific information available more rapidly and systematically monitoring guideline use.

An Evolutionary Medicine Perspective on Treatment of Pediatric Functional Abdominal Pain.

In a recent issue, Kovacic et al. analyze data from a randomized sham-controlled trial and show that pretreatment vagal efficiency, an index related to respiratory sinus arrhythmia, is a predictor of pain improvement in adolescents with functional abdominal pain when treated with auricular percutaneous electrical nerve field stimulation. The underlying premise is the polyvagal hypothesis, an explanatory framework for the evolution of the mammalian autonomic nervous system, which proposes that functional gastrointestinal disorders can result from a chronic maladaptive state of autonomic neural control mechanisms after traumatic stress. This is an opportunity for us to stimulate physicians' interest in evolutionary medicine.

Clinically Diagnosed Acute Diverticulitis in Outpatients: Misdiagnosis in Patients with Irritable Bowel Syndrome.

BACKGROUND: Physicians often diagnose diverticulitis and prescribe antibiotics in outpatients with abdominal pain and tenderness without other evidence. AIM: We investigated the misattribution of irritable bowel syndrome (IBS) symptoms to diverticulitis in outpatients. METHODS: In patients diagnosed with diverticulitis and dispensed antibiotics in an integrated healthcare system, we retrospectively compared 15,846 outpatients managed without computed tomography (CT) versus 3750 emergency department/inpatients who had CT. We assessed demographics and past history, including 17 symptom-based somatic and 11 mental disorders and three somatic-mental comorbidity pairs (dyads) coded over 3 years and seven drug classes dispensed over 1 year before diagnosis. RESULTS: Univariate analysis showed small intergroup demographic differences. Outpatients had increases in prior diverticulitis, including outpatient-managed episodes, total somatic diagnoses (p < .0001), eight somatic and three mental disorders (p ≤ .015), all three dyads (p ≤ .05), and dispensing of three drug classes (p ≤ .016). IBS had been diagnosed in 2399 (15.1 %) outpatients versus 361 (9.6 %) emergency department/inpatients (p < .0001), the greatest increase in any comorbidity. Emergency department/inpatients had no somatic comorbidity more often but more alcohol dependence, non-dependent drug abuse, and opioid dispensing (p ≤ .05). Regression analysis revealed outpatient care was independently positively associated with younger age, non-Hispanic white race/ethnicity, less Charlson comorbidity, diverticulitis history, IBS, chest pain, dyspepsia, fibromyalgia, low back pain, migraine, acute reaction to stress, and antispasmodic and anxiolytic dispensing and negatively associated with non-dependent drug abuse and opioid dispensing (p ≤ .0226). CONCLUSIONS: Multiple types of indirect and concordant evidence suggest misattribution of IBS pain to diverticulitis and unnecessary antibiotic therapy in outpatients.

Screening colonoscopy versus sigmoidoscopy: implications of a negative examination for cancer prevention and racial disparities in average-risk patients.

BACKGROUND: Both colonoscopy and flexible sigmoidoscopy are accepted procedures for colorectal cancer (CRC) screening in the United States. OBJECTIVE: To compare risk of CRC after negative findings on screening colonoscopy versus sigmoidoscopy and to evaluate racial/ethnic disparities in postscreening CRC. DESIGN: Retrospective, comparative cohort study. SETTING: Integrated community-based health-care system. PATIENTS: Average-risk patients 50 to 75 years of age with negative findings on an initial endoscopic screening examination from January 2000 to December 2010. INTERVENTIONS: Colonoscopy versus sigmoidoscopy as the initial screening procedure. MAIN OUTCOME MEASUREMENTS: Incident cases of CRC identified via a prospective internal cancer registry, risk of CRC determined by Cox regression adjusted for age, sex, race/ethnicity, and comorbidity. RESULTS: The study cohort included 138,297 patients (42,938 patients with negative findings on colonoscopy and 95,359 with negative findings on sigmoidoscopy). The median age was 57.9 years (interquartile range 53.0-64.1 years). Women comprised 51.8% of the cohort with 42.2% non-Hispanic white patients, 24.1% Hispanic patients, 10.7% non-Hispanic black patients, 9.7% Asian patients, and 13.3% other/unknown. A total of 241 cases of CRC was detected during 553,543 person-years of follow-up. The adjusted hazard ratio (HR) of postscreening CRC was 0.42 (95% confidence interval [CI], 0.28-0.64; P < .0001) for colonoscopy versus sigmoidoscopy. Risk reduction was primarily among proximal tumors (adjusted HR 0.30; 95% CI, 0.16-0.57). Non-Hispanic black patients were at higher risk of postscreening CRC compared with non-Hispanic white patients (adjusted HR 1.71; 95% CI, 1.20-2.42); however, this disparity was noted only in the sigmoidoscopy cohort. LIMITATIONS: Retrospective study with potential selection bias and residual confounding. CONCLUSIONS: Negative screening colonoscopy was associated with decreased incidence of subsequent CRC and a decrease in disparities compared with negative sigmoidoscopy findings in this large, community-based setting.

Torture Survivors and Asylum: Legal, Medical, and Psychological Perspectives.

Torture occurs worldwide. Survivors seeking asylum are detained and must complete a complicated legal process to prove a "well-founded fear of persecution" if returned to their home countries. Forensic evaluations guided by the United Nations Istanbul Protocol increase asylum grant rates. Medical evaluation emphasizes skin examination, which can provide strong evidence of torture. Female genital mutilation and cutting, a basis for asylum, is classified according to the World Health Organization. Many resettled refugees and foreign-born immigrants at urban health care facilities have been tortured, but few report it to physicians due to factors affecting both survivors and physicians. Specific torture methods can cause characteristic long-term sequelae. Painful somatic disorders of mind-body interaction and psychological disorders are common. Practices derived from cultural factors and traumatized individuals' feedback enhance management of survivors. Individual and group psychotherapy provide modest proven benefit, but assessment is limited. Physicians and psychotherapists should coordinate care.

Pediatric obesity and gallstone disease.

OBJECTIVES: The aim of the present study was to investigate the association between childhood and adolescent obesity, the risk of gallstones, and the potential effect modification by oral contraceptive use in girls. METHODS: For this population-based cross-sectional study, measured weight and height, oral contraceptive use, and diagnosis of cholelithiasis or choledocholithiasis were extracted from the electronic medical records of 510,816 patients ages 10 to 19 years enrolled in an integrated health plan, 2007-2009. RESULTS: We identified 766 patients with gallstones. The adjusted odds ratios (95% CI) of gallstones for under-/normal-weight (reference), overweight, moderate obesity, and extreme obesity in boys were 1.00, 1.46 (0.94%-2.27%), 1.83 (1.17%-2.85%), and 3.10 (1.99%-4.83%) and in girls were 1.00, 2.73 (2.18%-3.42%), 5.75 (4.62%-7.17%), and 7.71 (6.13%-9.71%), respectively (P for interaction sex × weight class <0.001). Among girls, oral contraceptive use was associated with higher odds for gallstones (odds ratio 2.00, 95% CI 1.66%-2.40%). Girls who used oral contraceptives were at higher odds for gallstones than their counterparts in the same weight class who did not use oral contraceptives (P for interaction weight class × oral contraceptive use 0.023). CONCLUSIONS: Due to the shift toward extreme childhood obesity, especially in minority children, pediatricians can expect to face increasing numbers of children and adolescents affected by gallstone disease.

Factors that predict relief from upper abdominal pain after cholecystectomy.

BACKGROUND & AIMS: Upper abdominal pain (UAP) in patients with gallstones is often treated by cholecystectomy but it frequently persists. We aimed to identify symptoms associated with relief. METHODS: We followed 1008 patients who received cholecystectomy for gallstones and UAP at the Mayo Clinic (Rochester, Minnesota) or Kaiser Permanente (San Diego, California) for 12 months. A validated, self-completed biliary symptoms questionnaire identified features of UAP, gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS); the questionnaire was given initially and 3 and 12 months after cholecystectomy, to identify features that predicted sustained relief of UAP. RESULTS: Five hundred ninety-four patients (59%) reported relief from UAP. Factors associated univariately (P < .05) with relief included frequency of UAP ≤1 per month, onset ≤1 year preoperatively, usual duration (30 minutes to 24 hours, most often in the evening or night), and severity >5/10. Compared to no features, multiple predictive features of UAP (frequency, onset, duration, or timing) were associated with increasing odds ratios (95% confidence interval) for relief: 1, 2, or 3 features (4.2 [1.1-16]; P = .03) and 4 features (6.3 [1.6-25]; P = .008). Negative univariate associations included lower abdominal pain (LAP), usual bowel pattern, nausea ≥1 per week, often feeling bloated or burpy, GERD, and/or IBS. There was an inverse association between relief and somatization; relief was not associated with postprandial UAP. Multivariable logistic regression analysis revealed independent associations (P < .05) with UAP frequency, onset, and nocturnal awakening, but inverse associations with lower abdominal pain, abnormal bowel pattern, and frequent bloated or burpy feelings. CONCLUSIONS: UAP features and concomitant GERD, IBS, and somatization determine the odds for relief from UAP after cholecystectomy.

Foot Torture (Falanga): Ten Victims with Chronic Plantar Hyperpigmentation.

BACKGROUND: Falanga is a widespread form of torture, but details of the chronic skin sequelae on physical examination are unreported. METHODS: In an organization dedicated to the care of torture victims, we prospectively documented examination findings in 10 consecutive, black African falanga victims. RESULTS: Ten individuals (8 men) suffered 1 or more episodes of falanga, most recently 9 to 29 months (9 cases) or 10 years (1 case) earlier. Examination revealed 3 to 50 or more pigmented macules, most greater than or equal to 0.5 cm in size, on both soles of all 10 victims. The degree of pigmentation and border distinctness of the lesions varied. Two cases had plantar tenderness. CONCLUSIONS: Plantar hyperpigmentation was present in all cases 9 months to 10 years after suffering falanga. This physical sign can support victims' legal requests for political asylum, and its recognition can aid physicians who care for torture victims.

Diseases and drugs that increase risk of acute large bowel ischemia.

BACKGROUND & AIMS: Information is limited on risk factors for acute large bowel ischemia (ALBI). We investigated diseases and drugs associated with ALBI. METHODS: We compared patients hospitalized with ALBI and controls through multivariate analysis of prior outpatient/emergency department/inpatient diagnoses and pharmacy dispensing records. RESULTS: There were 379 cases and 1516 controls (median age, 69 y; range, 25-97 y; 74.4% female). Disorders that were diagnosed in more cases than controls, based on univariate analysis (P < .05), included hypertension, diabetes, chronic obstructive pulmonary disease, atrial fibrillation, congestive heart failure, depression, asthma, coronary artery disease, dementia, rheumatoid arthritis, irritable bowel syndrome, dialysis dependency, diarrhea, and constipation. Drugs dispensed to more cases than controls were antihypertensives, opioids, statins, female hormones, potentially constipating drugs, histamine H(2)-antagonists, immunomodulators, digoxin, clopidogrel/ticlopidine, taxanes/vinca alkaloids, and antibiotics. In all cases, ALBI was associated independently with hypertension (adjusted odds ratio [AOR], 3.21, 95% confidence interval [CI]; 2.28-4.53; P < .0001), chronic obstructive pulmonary disease (AOR, 3.13; 95% CI, 2.06-4.75; P < .0001), diarrhea (AOR, 2.36; 95% CI, 1.13-4.89; P = .0218), atrial fibrillation (AOR, 2.21; 95% CI, 1.34-3.64; P = .0019), congestive heart failure (AOR, 1.94; 95% CI, 1.11-3.39; P = .0205), diabetes (AOR, 1.82; 95% CI, 1.31-2.53; P = .0004), antibiotics (AOR, 3.30; 95% CI, 2.19-4.96; P < .0001), opioids (AOR, 1.96; 95% CI, 1.43-2.67; P < .0001), and potentially constipating drugs (AOR, 1.75; 95% CI, 1.25-2.44; P = .0012). Analysis of only women revealed similar associations except for diarrhea plus rheumatoid arthritis (AOR, 3.27; 95% CI, 1.07-9.96; P = .0370), irritable bowel syndrome (AOR, 2.72; 95% CI, 1.04-7.14; P = .0424), and female hormones (AOR, 1.88; 95% CI, 1.30-2.73; P = .0009). CONCLUSIONS: Heterogeneous diseases and drugs increase the risk of ALBI, consistent with multifactorial pathogenesis.

Effect of physician education and patient counseling on inpatient nonsurgical percutaneous feeding tube placement rate, indications, and outcome.

BACKGROUND: The decision to place a percutaneous feeding tube (PFT) in patients who are at the end of life is multidimensional and often complicated. We assessed the effect of physician education and counseling for patients and their surrogates on inpatient nonsurgical (endoscopic and radiologic) PFT placement rates, indications, complications, and mortality. METHODS: In a pre-paid group practice, a geriatrician initiated a program of physician education and patient/surrogate counseling on the ethical and nutritional aspects of long-term enteral feeding. We compared rates of nonsurgical PFT placement (excluding those for cancer therapy or gastric decompression), indications, complications, and short- and long-term mortality in adult inpatients before (2004) and after (2005) the program. RESULTS: In 2004 and 2005, 115 and 60 inpatients underwent PFT placement, respectively. The annual number of hospital admissions was similar, but the rate of PFT placement declined (0.80% vs. 0.44%, P < 0.0001). The indications were cerebrovascular accident (42 [37%] versus 22 [37%]), dementia (15 [13%] versus 3 [5%]), other neurological disease (28 [24%] versus 16 [26%]), and miscellaneous disease (30 [26%] versus 19 [32%]); P > 0.05. Severe infectious complications occurred in 4 (3%) versus 0 (0%) patients, P > 0.05. Mortality (2004 versus 2005) at 30 days (23 [20%] versus 11 [18%]), 1 year (62 [54%] versus 29 [48%]) and 2 years (72 [63%] versus 31 [52%]) was similar, P > 0.05. CONCLUSION: A pilot program of educating referring physicians and counseling patients and their surrogates reduced the rate of inpatient PFT placement by nearly 50%. Indications, severe complications and short- and long-term mortality remained unchanged.

Misdiagnosis of Diverticulitis After a Prior Diagnosis of Irritable Bowel Syndrome (IBS).

INTRODUCTION: Irritable bowel syndrome (IBS) and diverticulitis share clinical features. Misdiagnosed diverticulitis can cause unnecessary antibiotic therapy. Among IBS and non-IBS patients, we compared outpatient, clinically diagnosed (no computed tomography) diverticulitis rates. Among primary-care, diverticulitis-diagnosed IBS patients, we assessed imaged diverticulosis and probable misdiagnosed diverticulitis. METHODS: Among 3836-patient IBS and 67,827-patient non-IBS cohorts identified from 2000 to 2002, we retrospectively compared the frequency of outpatient, clinically diagnosed, antibiotic-treated diverticulitis from 2003 to endpoints of December 31, 2017, disenrollment, or death. In IBS patients, we reviewed records of initial, primary care-managed episodes for misdiagnosis. RESULTS: In 3836 clinically diagnosed IBS and 63,991 non-IBS cohorts, followup (median [interquartile range]) was 12.4 (3.9 to 15.0) years versus 10.2 (3.0 to 15.0) years, respectively (P < .001). The incidence rate/1000 patient-years (95% CI) of diagnosed diverticulitis was 14.0 (12.1 to 16.3) and 4.2 (4.0 to 4.5), respectively, (crude incidence rate ratio, 3.3 [2.8-3.9]; P < .001). Of examined features, the diagnosis of IBS was most strongly associated with clinically diagnosed diverticulitis (adjusted incidence rate ratio [95% CI]; 2.64 [2.21-3.15], P < .001). Of initial diverticulitis diagnoses in 189 IBS patients, objective evidence-based diagnosis revision or exclusion occurred in 12 (6.3%), including 6 hospitalized; 29 (15.3%) had colon imaging before and/or afterward without diverticulosis reported; 143 (75.1%) had image-documented diverticulosis; and 6 (3.2%) had no imaging. CONCLUSIONS: Outpatient, clinically diagnosed, antibiotic-treated diverticulitis was increased 3-fold in IBS patients. Primary care clinical misdiagnosis of initial episodes occurred in 1 of 5 patients, but additional misdiagnosis due to misattribution of IBS pain to diverticulitis is suggested.