All FODMAPs Aren't Created Equal: Results of a Randomized Reintroduction Trial in Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: A diet low in fermentable oligo, di, monosaccharides, and polyols (FODMAPs) is one of the recommended management strategies for irritable bowel syndrome (IBS). However, while effective, adherence to restricting dietary FODMAPs can be challenging and burdensome. The question remains whether limiting all FODMAPs during the restrictive phase of the diet is necessary for symptomatic improvement in the dietary treatment of IBS, or if targeting selected groups of FODMAPs for restriction is sufficient for clinical response. Our study aimed to determine which individual FODMAPs are most likely to lead to symptom generation in patients with IBS who have improved with fodmap restriction. METHODS: Patients meeting Rome IV criteria for IBS were invited to participate in a 12-week study to identify individual FODMAP sensitivities. Those subjects who demonstrated symptom improvement after a 2- to 4-week open-label FODMAP elimination period were recruited to a 10-week blinded-phased FODMAP reintroduction phase of 7 days for each FODMAP. Throughout the study period, daily symptom severity (0-10 point numerical rating system) was recorded. A mixed effect statistical analysis model was used. RESULTS: Between 2018 and 2020, 45 subjects were enrolled. Twenty-five subjects improved with FODMAP elimination, and 21 patients continued into the reintroduction phase of the study. Fructans and galacto-oligosaccharides (GOS) both were associated with worsened abdominal pain (P = .007 and P = .04, respectively). GOS were associated with an increase in bloating (P = 03). Both bloating and abdominal pain worsened throughout the study, regardless of the FODMAP reintroduction (P = .006). CONCLUSION: Our results suggest that the reintroduction of select FODMAPs may be responsible for symptom generation in patients with IBS who have responded to a low FODMAP diet, and provide a strong rationale for performing a future trial comparing the treatment effects of a limited low-FODMAP diet and a standard low-FODMAP diet. CLINICALTRIALS: GOV: NCT03052439.

A New Score for Quantifying Adherence to a Cancer-Preventive Mediterranean Diet.

Herein a Mediterranean Cancer Preventive Diet Score (MCAP Score) is proposed to quantify adherence to both traditional Mediterranean fat intakes and the current dietary recommendations for cancer prevention. The scoring uses research-backed cutoff values, unlike other scores that are based on a population-specific median value. The MCAP score awards positive points for seven preventive food categories, including Mediterranean fats (monounsaturated fats, ω-3 fatty acids) associated with reduced adiposity, and negative points for four food categories associated with increased cancer risk, including ultra-processed foods. In a randomized trial of 120 persons at increased risk of colon cancer, the baseline MCAP Score averaged seven of 20 possible points. Counseling for a Healthy Diet or a Mediterranean Diet improved the score to either 11 or 13 points, respectively, and the highest score observed in any individual was 20 points. The MCAP Score was correlated with serum carotenoids and serum ω-3 fatty acids, and improvements in the score were associated with weight loss over six months of study. The MCAP Score is therefore proposed as a new method to assess adherence to a Mediterranean type of diet for cancer prevention using absolute criteria that will facilitate comparisons of dietary intakes across studies.

Yogurt consumption and colorectal polyps.

Diet modifies the risk of colorectal cancer (CRC), and inconclusive evidence suggests that yogurt may protect against CRC. We analysed the data collected from two separate colonoscopy-based case-control studies. The Tennessee Colorectal Polyp Study (TCPS) and Johns Hopkins Biofilm Study included 5446 and 1061 participants, respectively, diagnosed with hyperplastic polyp (HP), sessile serrated polyp, adenomatous polyp (AP) or without any polyps. Multinomial logistic regression models were used to derive OR and 95 % CI to evaluate comparisons between cases and polyp-free controls and case-case comparisons between different polyp types. We evaluated the association between frequency of yogurt intake and probiotic use with the diagnosis of colorectal polyps. In the TCPS, daily yogurt intake v. no/rare intake was associated with decreased odds of HP (OR 0·54; 95 % CI 0·31, 0·95) and weekly yogurt intake was associated with decreased odds of AP among women (OR 0·73; 95 % CI 0·55, 0·98). In the Biofilm Study, both weekly yogurt intake and probiotic use were associated with a non-significant reduction in odds of overall AP (OR 0·75; 95 % CI 0·54, 1·04) and (OR 0·72; 95 % CI 0·49, 1·06) in comparison with no use, respectively. In summary, yogurt intake may be associated with decreased odds of HP and AP and probiotic use may be associated with decreased odds of AP. Further prospective studies are needed to verify these associations.

PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk.

Dietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62, P trend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (P trend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.

Nature, prevalence and risk factors of alcohol use in an urban slum of Southern India.

BACKGROUND: There is a paucity of data on the use of alcohol in urban slums of southern India. METHODS: We screened 2811 men for alcohol use via a household-level census in an urban slum in Vellore, Tamil Nadu, and interviewed 220 age- and area-matched pairs of men drinkers and non-drinkers to examine factors associated with alcohol use. Alcohol Use Disorder Identification Test (AUDIT), a standard instrument, was used to assess risk levels of drinking of 354 drinkers. Prevalence rates were calculated using age- adjusted direct standardization. Odds ratios (ORs) of drinking status and higher-risk drinking were calculated using conditional logistic regression and ordinal logistic regression, respectively. RESULTS: Among all men, we estimated that 46.1% consumed alcohol and 31.4% were hazardous drinkers (19% increased-risk, 7.7% high-risk and 4.7% dependent drinkers). Factors associated with alcohol use were: manual labour occupations (OR 2.08); presence of a common mental disorder (OR 1.50) and smoking (OR 2.08); while Muslim religion was protective (OR 0.43). Factors associated with higher-risk alcohol use were: being reported as a non-drinker during the census (OR 3.96); presence of a common mental disorder (OR 3.83); smoking (OR 1.78); drinking before legal age of 21 years (OR 2.71); spending more than `100 per day on alcohol (OR 6.17); and mainly drinking Indian-made foreign liquor (OR 5.45). CONCLUSION: High prevalence of hazardous drinking and the factors associated with it suggest the need for population- wide interventions and further investigations to effectively reduce hazardous alcohol use and its harmful effects.

Wood cookstove use is associated with gastric cancer in Central America and mediated by host genetics.

Biomass cookstove food preparation is linked to aero-digestive cancers, mediated by ingested and inhaled carcinogens (e.g., heterocyclic amines, and polycyclic aromatic hydrocarbons). We investigated the association between gastric adenocarcinoma, wood cookstove use, H. pylori CagA infection and risk modification by variants in genes that metabolize and affect the internal dose of carcinogens. We conducted a population-based, case-control study (814 incident cases, 1049 controls) in rural Honduras, a high-incidence region with a homogeneous diet and endemic H. pylori infection, primarily with the high-risk CagA genotype. We investigated factors including wood cookstove use, H. pylori CagA serostatus, and 15 variants from 7 metabolizing genes, and the interactions between wood stove use and the genetic variants. Male sex (OR 2.0, 1.6-2.6), age (OR 1.04, 1.03-1.05), wood cookstove use (OR 2.3, 1.6-3.3), and CagA serostatus (OR 3.5, 2.4-5.1) and two SNPs in CYP1B1 (rs1800440 and rs1056836) were independently associated with gastric cancer in multivariate analysis. In the final multivariate model, a highly significant interaction (OR 3.1, 1.2-7.8) was noted between wood cookstove use and the rs1800440 metabolizing genotype, highlighting an important gene-environment interaction. Lifetime wood cookstove use associates with gastric cancer risk in the high-incidence regions of Central America, and the association is dependent on the rs1800440 genotype in CYP1B1. H. pylori CagA infection, wood cookstove use and the rs1800440 genotype, all of which are highly prevalent, informs who is at greatest risk from biomass cookstove use.

A Predictive Model to Identify Complicated Clostridiodes difficile Infection.

Background: Clostridioides difficile infection (CDI) is a leading cause of health care-associated infection and may result in organ dysfunction, colectomy, and death. Published risk scores to predict severe complications from CDI demonstrate poor performance upon external validation. We hypothesized that building and validating a model using geographically and temporally distinct cohorts would more accurately predict risk for complications from CDI. Methods: We conducted a multicenter retrospective cohort study of adults diagnosed with CDI. After randomly partitioning the data into training and validation sets, we developed and compared 3 machine learning algorithms (lasso regression, random forest, stacked ensemble) with 10-fold cross-validation to predict disease-related complications (intensive care unit admission, colectomy, or death attributable to CDI) within 30 days of diagnosis. Model performance was assessed using the area under the receiver operating curve (AUC). Results: A total of 3646 patients with CDI were included, of whom 217 (6%) had complications. All 3 models performed well (AUC, 0.88-0.89). Variables of importance were similar across models, including albumin, bicarbonate, change in creatinine, non-CDI-related intensive care unit admission, and concomitant non-CDI antibiotics. Sensitivity analyses indicated that model performance was robust even when varying derivation cohort inclusion and CDI testing approach. However, race was an important modifier, with models showing worse performance in non-White patients. Conclusions: Using a large heterogeneous population of patients, we developed and validated a prediction model that estimates risk for complications from CDI with good accuracy. Future studies should aim to reduce the disparity in model accuracy between White and non-White patients and to improve performance overall.

Oral Microbiome Community Composition in Head and Neck Squamous Cell Carcinoma.

The impact of the oral microbiome on head and neck cancer pathogenesis and outcomes requires further study. 16s rRNA was isolated and amplified from pre-treatment oral wash samples for 52 cases and 102 controls. The sequences were binned into operational taxonomic units (OTUs) at the genus level. Diversity metrics and significant associations between OTUs and case status were assessed. The samples were binned into community types using Dirichlet multinomial models, and survival outcomes were assessed by community type. Twelve OTUs from the phyla Firmicutes, Proteobacteria, and Acinetobacter were found to differ significantly between the cases and the controls. Beta-diversity was significantly higher between the cases than between the controls (p < 0.01). Two community types were identified based on the predominant sets of OTUs within our study population. The community type with a higher abundance of periodontitis-associated bacteria was more likely to be present in the cases (p < 0.01), in older patients (p < 0.01), and in smokers (p < 0.01). Significant differences between the cases and the controls in community type, beta-diversity, and OTUs indicate that the oral microbiome may play a role in HNSCC.

Viremia and HIV-1 drug resistance mutations among patients receiving second-line highly active antiretroviral therapy in Chennai, Southern India.

BACKGROUND: A cross-sectional study among individuals receiving second-line antiretroviral treatment was conducted to report on the level of detectable viremia and the types of drug resistance mutations among those with detectable human immunodeficiency virus (HIV) type 1 plasma viral loads (PVLs). METHODS: PVLs were measured using Abbott m2000rt real-time polymerase chain reaction, and genotyping was performed with the ViroSeq genotyping system, version 2.0, and ViroSeq analysis software, version 2.8. RESULTS: Of 107 patient plasma specimens consecutively analyzed, 30 (28%) had undetectable PVLs (<150 copies/mL), and 77 (72%) were viremic with a median PVL of 5450 copies/mL (interquartile range, 169-1 997 967). Sequencing was done for 107 samples with PVLs >2000 copies/mL: 33 patients (73%) had 1 of the protease (PR) inhibitor mutations; 41 (91%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; 33 (73%) had non-NRTI (NNRTI) mutations; and 30 (66.7%) had both NRTI and NNRTI mutations. Triple-class resistance to NRTIs, NNRTIs, and PR inhibitors was observed in 24 (53%) patients. Based on the mutational profiles observed, all 45 sequences were susceptible to darunavir and tipranavir, whereas 47% showed resistance to lopinavir, 58% showed resistance to atazanavir, and >60% showed resistance to saquinavir, indinavir, nelfinavir, and fosamprenavir. CONCLUSIONS: The results of the study showed that the majority of patients receiving second-line antiretroviral therapy started to accumulate PR resistance mutations, and the mutation profiles suggest that darunavir might be the drug of choice for third-line regimens in India.

Factors associated with false-positive results from fingerstick OraQuick ADVANCE rapid HIV 1/2 antibody test.

OBJECTIVE: Identify factors associated with false-positive rapid HIV antibody tests. DESIGN: This retrospective cohort study with nested case-controls involved patients tested for HIV by Boston Medical Center (BMC) affiliates. METHODS: Cases had a reactive fingerstick OraQuick ADVANCE rapid HIV 1/2 antibody test and a negative Western blot. Controls had nonreactive rapid tests. We compared the prevalence of HIV risk factors between cases and the total nonreactive population and the prevalence of other clinical factors between cases and controls. RESULTS: Of the 15 094 tests, 14 937 (98.9%) were negative and 11 (0.07%) were false positives (specificity of 99.9%). Cases were more likely to have had an HIV-infected sex partner and to be tested at certain sites compared to true negatives. More cases than controls had O-negative blood type. CONCLUSION: O-negative blood type and sex with an HIV-infected person may increase false-positive HIV fingerstick results. More targeted studies should examine these risk factors.

Adult-Attained Height and Colorectal Cancer Risk: A Cohort Study, Systematic Review, and Meta-Analysis.

BACKGROUND: The influence of anthropometric characteristics on colorectal neoplasia biology is unclear. We conducted a systematic review and meta-analysis to determine if adult-attained height is independently associated with the risk of colorectal cancer or adenoma. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, and Web of Science from inception to August 2020 for studies on the association between adult-attained height and colorectal cancer or adenoma. The original data from the Johns Hopkins (Baltimore, MD) Colon Biofilm study was also included. The overall HR/OR of colorectal cancer/adenoma with increased height was estimated using random-effects meta-analysis. RESULTS: We included 47 observational studies involving 280,644 colorectal cancer and 14,139 colorectal adenoma cases. Thirty-three studies reported data for colorectal cancer incidence per 10-cm increase in height; 19 yielded an HR of 1.14 [95% confidence interval (CI), 1.11-1.17; P < 0.001), and 14 engendered an OR of 1.09 (95% CI, 1.05-1.13; P < 0.001). Twenty-six studies compared colorectal cancer incidence between individuals within the highest versus the lowest height percentile; 19 indicated an HR of 1.24 (95% CI, 1.19-1.30; P < 0.001), and seven resulting in an OR of 1.07 (95% CI, 0.92-1.25; P = 0.39). Four studies reported data for assessing colorectal adenoma incidence per 10-cm increase in height, showing an overall OR of 1.06 (95% CI, 1.00-1.12; P = 0.03). CONCLUSIONS: Greater adult attained height is associated with an increased risk of colorectal cancer and adenoma. IMPACT: Height should be considered as a risk factor for colorectal cancer screening.

Colorectal Cancer and Diet: Risk Versus Prevention, Is Diet an Intervention?

Colorectal cancer is the third most common cause of cancer in men and women in the world. Epidemiologic research approximates that half of colon cancer risk is preventable by modifiable risk factors, including diet. This article reviews prior studies involving certain food items and their relation to colorectal cancer, to elucidate whether diet can be a potential intervention.

Self-reported Metabolic Risk Factor Associations with Adenomatous, Sessile Serrated, and Synchronous Adenomatous and Sessile Serrated Polyps.

Studies have found a positive association between metabolic risk factors, such as obesity and diabetes, and adenomatous polyps (AP). However, fewer studies have assessed the association between sessile serrated polyps (SSP) or synchronous diagnosis of APs and SSPs (synch polyps). Study participants (N = 1,370; ages 40-85) undergoing screening colonoscopy were enrolled between August 2016 and February 2020. Self-reported metabolic risk factors, including diabetes, hypertension, hyperlipidemia, and overweight/obesity, were evaluated for associations with new diagnoses of APs, SSPs, and synch polyps at the present colonoscopy. Average participant age was 60.73 ± 8.63 (SD) years; 56.7% were female and 90.9% white. In an assessment of individual metabolic risk factors, adjusted for age, sex, race, and smoking status, increased body mass index (BMI; overweight or obese vs. normal BMI of <25 kg/m2) was associated with an increased odds for new onset of colon APs (P trend < 0.001) as was a diagnosis of diabetes [adjusted conditional OR (aCOR) = 1.59 (1.10-2.29)]. No associations were seen between the metabolic risk factors and onset of SSPs. Being obese or hypertensive each increased the odds of new onset of synch polyps with aCOR values of 2.09 (1.01-4.32) and 1.79 (1.06-3.02), respectively. Self-reported risk factors may help assess polyp type risk. Because SSPs and synch polyps are rare, larger studies are needed to improve our understanding of the contribution of these factors to polyp risk. These data lead us to hypothesize that differences in observed metabolic risk factors between polyp types reflect select metabolic impact on pathways to colorectal cancer. PREVENTION RELEVANCE: Self-reported medical history provides valuable insight into polyp risk, potentially enabling the use of larger retrospective studies of colonoscopy populations to assess knowledge gaps. More aggressive colonoscopy screening, critical to colorectal cancer prevention, may be considered in populations of individuals with metabolic risk factors and modifiable lifestyle risk factors.

Dried blood spots versus plasma for the quantitation of HIV-1 RNA using a real-Time PCR, m2000rt assay.

High costs and stringent requirements for storage and transport of plasma, often prohibit the availability of HIV viral load quantification in resource-limited settings. Dried blood spots (DBS) represent a better method of specimen collection that removes many of these logistical and technical limitations. The present study aimed to assess the performance of the Abbott m2000rt assay for quantitation of HIV-1 RNA in DBS specimens using plasma as a "gold standard" for comparison. One hundred paired DBS and plasma specimens were collected from patients infected with HIV, who were 18 years and older during routine visits to a private tertiary-care clinic in Chennai, India. HIV-1 RNA was extracted manually and then detected using the m2000rt assay. The mean plasma and DBS viral loads were 4.27 (95% CI: 2.65, 5.88) and 4.14 (95% CI: 1.96, 6.32) log copies/mL, respectively. The overall sensitivity of DBS reached 95%; with sensitivities of 62%, 88% and 100% when stratified by viral load ranges of ≤1000, 1000-3000 and >3000 copies/mL, respectively. An over quantitation of the viral load with DBS was observed in pairs with plasma viral load<3000 copies/mL [d=-0.3 log copies/mL (ranging from -0.1 to 0.6 log copies/mL)]. The study showed a strong concordance in RNA levels between plasma and DBS. The use of DBS specimens should be considered for HIV monitoring and for detection of virologic failure in resource-limited settings.

Hormonal contraception and risk of bacterial vaginosis diagnosis in an observational study of women attending STD clinics in Baltimore, MD.

BACKGROUND: The protective effect of hormonal contraception may offer a potential intervention against bacterial vaginosis (BV). STUDY DESIGN: Three hundred thirty reproductive-age women enrolled in a contraceptive program from April 2005 to October 2006 at two sexually transmitted diseases clinics in Baltimore, MD. Participants were supplied with hormonal contraceptives of their choice and followed prospectively. BV was diagnosed by Amsel's criteria. Results from population-level analysis were compared to a case-crossover analysis. RESULTS: BV was diagnosed in 189 (13.0%) of the visits among 133 (40.3%) women. In the population-level analysis, the use of progestin-only and combined contraception was associated with a decreased risk of BV compared to intervals of no hormonal contraceptive use [adjusted odds ratio (AOR): 0.42 (95% CI: 0.20-0.88) and AOR: 0.66 (95% CI: 0.39-1.10), respectively]. The case-crossover analysis demonstrated a similar trend in findings. CONCLUSION: Hormonal contraception was associated with a decreased risk of BV in an STD clinic cohort.