Renal dysfunction in routine proton-pump inhibitor use may be linked to comorbidities: A real-world observational study.

INTRODUCTION: The use of proton-pump inhibitors (PPI) is linked with infrequent but serious adverse events, including acute kidney injury, chronic kidney disease (CKD) and progression of CKD. Data on renal safety in routine use of PPI are more relevant to clinical practice. We studied whether such use of PPI is associated with renal dysfunction. METHODS: Patients taking PPI for at least six weeks had serum creatinine tested pre (n = 200) and post (n = 180) recruitment. These patients were then advised to follow-up: those taking PPI for at least 90 days in the next six months (n = 77) and at least another 90 days in the following six months (n = 50), had serum creatinine tested at such follow-up. Renal dysfunction was defined as any increase in serum creatinine level above baseline. RESULTS: The 200 patients recruited had mean age 39.6 (SD 9.2) years. Ninety-eight (49%) patients had a history of previous PPI use (median six months; interquartile range [IQR] 3-24). Only 20 (11.1%) patients at six weeks, 11 (14.3%) at six months and six (12%) at one year had increase in creatinine level; a majority of them had less than 0.3 mg/dL increase. Ten of these 20 (six weeks), five of 11 (six months) and five of six (one year) had other risk factors for renal dysfunction. No patient developed CKD during the study period. CONCLUSIONS: Mild and non-progressive increase in serum creatinine occurred in 10% to 15% of patients on routine PPI use. A majority of them had other risk factors. Small sample size and short follow-up duration are a few limitations of this study.

Detection of Wuchereria bancrofti DNA in wild caught vector and non-vector mosquitoes: implications for elimination of lymphatic filariasis.

BACKGROUND: Transmission Assessment Survey (TAS) is the WHO recommended method used for decision-making to stop or continue the MDA in lymphatic filariasis (LF) elimination programme. The WHO has also recommended Molecular Xenomonitoring (MX) of LF infection in vectors as an adjunct tool in settings under post-MDA or validation period. Screening of non-vectors by MX in post-MDA / validation settings could be useful to prevent a resurgence of LF infection, as there might be low abundance of vectors, especially in some seasons. In this study, we investigated the presence of LF infection in non-vectors in an area endemic for LF and has undergone many rounds of annual MDA with two drugs (Diethylcarbamazine and Albendazole, DA) and two rounds of triple drug regimens (Ivermectin + DA). METHODS AND RESULTS: Mosquitoes were collected from selected villages of Yadgir district in Karnataka state, India, during 2019. A total of 680 female mosquitoes were collected, identified morphologically by species and separated as pools. The female mosquitoes belonging to 3 species viz., Anopheles subpictus, Culex gelidus and Culex quinquefaciatus were separated, pooled, and the DNA extracted using less expensive method and followed by LDR based real-time PCR assay for detecting Wuchereria bancrofti infection in vector as well as non-vector mosquitoes. One pool out of 6 pools of An. subpictus, 2 pools out of 6 pools of Cx. gelidus, and 4 pools out of 8 pools of Cx. quinquefaciatus were found to be positive for W. bancrofti infection by RT-PCR. The infection rate in vectors and non-vectors was found to be 1.8% (95% CI: 0.5-4.2%) and 0.9% (95% CI: 0.2-2.3%), respectively. CONCLUSIONS: Our study showed that non-vectors also harbour W. bancrofti, thus opening an opportunity of using these mosquitoes as surrogate vectors for assessing risk of transmission to humans in LF endemic and post MDA areas.

Self-reported food intolerances in an Indian population: Need for individualization rather than a universal low-FODMAP diet.

Background and Aim: Low-fermentable oligo-, di-, and monosaccharides and polyol (FODMAP) diets have been recommended for individuals with food intolerance and irritable bowel syndrome (IBS). Individual food intolerances may, however, not correspond to the FODMAP content alone. Methods: We conducted a survey on self-reported intolerance to articles of food commonly identified as high FODMAP in 400 healthy Indian subjects (median age 40 years; 69% men) and 204 consecutive consenting patients with IBS (median age 36 years; 58% men). Results: One-hundred seventy-nine (44.8%) healthy subjects and 147 (72.1%) patients with IBS reported some food intolerance (P < 0.00001); the latter reported intolerance to all items (except nuts) more frequently than healthy subjects. The prevalence, however, varied from 2.5 to 32%. Milk intolerance was reported equally commonly by healthy subjects and patients (23% vs 29.9%). Twenty-three (11.3%) patients and no healthy subjects reported wheat sensitivity. The IBS diarrhea subgroup reported intolerance to milk, pulses, capsicum, cauliflower, leafy vegetables, and dry fruits more frequently than the constipation subgroup. Conclusion: From among a list of high-FODMAP items, individuals' intolerance varied widely, suggesting that individuals should be the final judge in deciding their elimination diets rather than devise them based on the FODMAP content alone. As in the West, food intolerance was reported more commonly by patients with IBS, especially those with diarrhea, than by healthy individuals. Also noteworthy is the low prevalence of milk intolerance in a subcontinent labeled as high in lactose intolerance. Unlike in the West, wheat intolerance was not reported by any healthy individual.

A prospective study of inflammatory bowel disease phenotypes in extremes of age and comparison with adults.

BACKGROUND AND AIMS: Pediatric and elderly inflammatory bowel disease (IBD) are less explored, often in retrospective studies. The pediatric group has a more extensive and aggressive disease phenotype requiring aggressive treatments, whereas the elderly group may have less aggressive diseases. METHODS: We prospectively compared disease characteristics of a single center cohort of IBD patients (pediatric age ≤ 16 years; adults 17 to 59 years; and elderly ≥ 60 years) seen between September 2018 and November 2019 with at least six months of follow-up. RESULTS: Total 266 IBD patients (137 males) included 47 pediatric, 175 adults and 44 elderly patients. Among ulcerative colitis (UC) patients, pancolitis was more common in the pediatric group (p = 0.018), while the elderly group had more indolent behaviors and infrequent extraintestinal manifestations (p = 0.005). Among patients with Crohn's disease (CD), the pediatric group had more often colonic diseases (p = 0.02) and the elderly, ileal diseases (p = 0.04). The disease behavior was similar in the three age groups. Perianal disease was least common in elderly CD patients (p = 0.03). There was no treatment difference among different age groups in UC. In CD, pediatric patients needed biologics more frequently (p = 0.005), while elderly CD patients less frequently required steroids, biologics, immunosuppressants and surgery (p < 0.05). CONCLUSIONS: We noted differences compared to western literature such as colonic location in pediatric CD and ileal location in elderly CD. Perianal disease was less frequent in the elderly CD group. There was no difference in treatment in the three age groups in UC, while there were no inter-age-group disease behavioral differences for UC and CD.

Indian consensus statements on irritable bowel syndrome in adults: A guideline by the Indian Neurogastroenterology and Motility Association and jointly supported by the Indian Society of Gastroenterology.

The Indian Neurogastroenterology and Motility Association (INMA), earlier named the Indian Motility and Functional Diseases Association developed this evidence-based practice guidelines for the management of irritable bowel syndrome (IBS). A modified Delphi process was used to develop this consensus containing 28 statements, which were concerning diagnostic criteria, epidemiology, etiopathogenesis and comorbidities, investigations, lifestyle modifications and treatments. Owing to the Coronavirus disease-19 (COVID-19) pandemic, lockdowns and mobility restrictions, web-based meetings and electronic voting were the major tools used to develop this consensus. A statement was regarded as accepted when the sum of "completely accepted" and "accepted with minor reservation" voted responses were 80% or higher. Finally, the consensus was achieved on all 28 statements. The consensus team members are of the view that this work may find use in teaching, patient care, and research on IBS in India and other nations.

Dysbiosis in Irritable Bowel Syndrome.

The human gut microbiota fosters the development of a dynamic group of microorganisms impacted by diverse variables that include genetics, diet, infection, stress, ingested drugs, such as antibiotics and small intestine bacterial overgrowth (SIBO) as well as the gut microbiota itself. These factors may influence the change in microbial composition, which results in dysbiosis (microbial imbalance) and exposes the gut to pathogenic insults. Dysbiosis is incidental to the etiology of inflammatory diseases such as irritable bowel syndrome (IBS) and metabolic diseases, including type 2 diabetes and obesity. IBS exhibits different symptoms like abdominal pain or discomfort, distention/bloating, and flatulence. To treat IBS, modification of dysregulated gut microbiota can be done using treatment strategies like a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, antibiotics that cannot be absorbed like rifaximin and neomycin, probiotics and prebiotics, and fecal microbiota transplantation (FMT). The remedial modalities in the existing literature have been demonstrated to be efficacious in the prevention and mitigation of IBS. Additionally, newer curative approaches with serum-derived bovine immunoglobulin (SBI) are an effective option. The focal point of the review paper is the pathophysiology of IBS, mainly due to dysbiosis and the various factors that advance dysbiosis. Here, we have also discussed the different treatment strategies targeting dysbiosis that effectively treat IBS. How to cite this article: Abraham P, Pratap N. Dysbiosis in Irritable Bowel Syndrome. J Assoc Physicians India 2023;71(9):75-81.

Ten-day concomitant and sequential therapy for Helicobacter pylori effective in region with high antibiotic resistance rates.

BACKGROUND: Increasing antibiotic-resistant Helicobacter pylori (H. pylori) strains complicate efforts to eradicate infection. In regions with high dual resistance to both clarithromycin and metronidazole, bismuth quadruple therapy is recommended. But, with lack of easy availability of bismuth, the (non-bismuth) concomitant and sequential regimens are used commonly as first-line therapy. Recent reports indicate suboptimal results with sequential therapy in such regions. We aimed to compare the efficacy of concomitant therapy vs. sequential therapy in the eradication of H. pylori in a region with high antibiotic resistance rates, and to compare adherence rates and adverse events with the regimens. METHODS: One hundred and twenty-four consecutive H. pylori-infected patients (diagnosed using rapid urease test or urea breath test) were randomized to receive sequential or concomitant therapy for 10 days each. Four weeks after treatment completion, urea breath test was done to confirm eradication of the infection. Cure rates were compared between the two regimens and note was made of adherence rates and adverse events. RESULTS: Concomitant therapy showed a statistically non-significant higher cure rate compared to sequential therapy in intention-to-treat (87.1% vs. 81.4%%, p = 0.46) and per-protocol (94.7% vs. 83.9%, p = 0.07) analyses. Both the regimens were well tolerated and showed similar adherence rates (p = 1.00) and incidence of adverse events (p = 0.44). CONCLUSION: In a region with high dual resistance, both concomitant and sequential therapy for H. pylori infection achieved eradication rates >80%, but concomitant therapy showed a statistically non-significant higher cure rate, with similar adherence and adverse event profiles.

Intra- and inter-observer agreement in the classification of dyssynergic defecation on high-resolution anorectal manometry using water-perfusion system.

BACKGROUND AND AIMS: Dyssynergic defecation (DD) classified on anorectal manometry is based on variations in anal sphincter pressures and rectal pressure generated during bearing down. There is a paucity of data on intra- and inter-observer agreement in the classification of DD on high-resolution anorectal manometry (HRAM) using a water-perfusion system. METHODS: This cross-sectional observational study was conducted between June 2014 and May 2016 on 70 adult patients with DD. Observer 1 did the baseline analysis and reanalyzed the readings at least 6 months later, blinded to the initial analysis results (intra-observer variability). Four other blinded observers (5-25 years in anorectal manometry and minimum 5 years of experience in HRAM) then individually analyzed the manometry data (inter-observer variability). RESULTS: Intra-observer agreement was excellent (kappa 0.862) for classifying DD. Agreement between the six observations (i.e. two from observer 1 and four from independent observers) was also good (kappa 0.632). The highest agreement was for type 4 DD (kappa 0.738), followed by type 1 (0.680), type 2 (0.664), and type 3 (0.537). Cronbach's alpha value was 0.93, suggesting excellent internal consistency. CONCLUSION: The diagnosis of the types of DD on anorectal manometry using a water-perfusion system has excellent intra-observer and good inter-observer agreement .

Detection of recombinant dengue virus 2 NS1 protein in Aedes aegypti mosquitoes using commercial Dengue NS1 ELISA kit.

Dengue, a vector-borne disease remains as one of the most serious public health problems globally. Incidence of this disease is on an increasing trend and currently over a billion people in tropical and subtropical regions are at risk. In the absence of an operational vaccine, prevention of dengue virus (DENV) is primarily focused upon controlling mosquito vectors. Mosquito vector surveillance programmes require simple and rapid tools to detect mosquitoes infected with DENV. Here, we tested the commercially available DENV Detect™ NS1 ELISA kit (InBios International, Inc.) for detection of recombinant DENV-NS1 protein in Aedes mosquito samples. The kit was evaluated to find out the minimum detection limit of recombinant DENV-2 NS1 protein following the manufacturer's instructions. Initially, the NS1 protein detection threshold of the kit was determined and later the assay was standardized for detection of NS1 protein in Aedes aegypti mosquito pools containing 5, 10 and 25 mosquitoes. The ELISA kit displayed high sensitivity towards detection of recombinant dengue virus-2 NS1 protein in mosquito pools (up to 25 mosquitoes per pool) at 25 pico gram concentration. Since the commercial NS1 ELISA is highly sensitive and follows a very simple procedure, it could be employed for DENV surveillance in Aedes aegypti mosquitoes, after carrying out laboratory and field bioassays with DENV infected specimens.

Risk factors for bleeding in people living with hemophilia A and B treated with regular prophylaxis: A systematic review of the literature.

BACKGROUND: Knowledge about the risk for bleeding in patients with hemophilia (PWH) would be relevant for patients, stakeholders, and policy makers. OBJECTIVES: To perform a systematic review of the literature on risk assessment models (RAMs) and risk factors for bleeding in PWH on regular prophylaxis. METHODS: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from inception through August 2019. In duplicate, reviewers screened the articles for inclusion, extracted data, and assessed the risk for bias using the Quality in Prognostic Studies (QUIPS) tool. A qualitative synthesis of the results was not performed due to high heterogeneity in risk factors, outcomes definition and measurement, and statistical analysis of the results. RESULTS: From 1843 search results, 10 studies met the inclusion criteria. No RAM for the risk for bleeding in PWH was found. Most studies included only PWH A or both PWH A and B and were conducted in North America or Europe. Only one study had a low risk for bias in all the domains. Eight categories of risk factors were identified. The risk for bleeding was increased when factor levels were lower and in people with a significant history of bleeding or who engaged in physical activities involving contact. CONCLUSIONS: Our findings suggest that plasma factor levels, history of bleeds, and physical activity should be considered for the derivation analysis when building a RAM for bleeding in PWH, and the role of other risk factors, including antithrombotic treatment and obesity, should be explored.

Factors influencing circulating microRNAs as biomarkers for liver diseases.

MicroRNAs (microRNAs) have been implicated to play crucial roles in various liver diseases. Hepatic microRNAs are released in to the circulation in a systematic fashion, and are, therefore, being extensively explored for their role as prognostic or diagnostic markers or therapeutic targets for numerous hepatic diseases. Advantages such as disease- or tissue-specific expression, and ease of detection have implicated circulating microRNAs (c-microRNAs) as the most desirable candidate for biomarker studies. Although several studies have explored c-microRNAs in serum or plasma, consistency of detection of microRNAs remains demanding because of many biological and methodological challenges. Lack of methodological consensus has limited the universal use of c-microRNAs as potential prognostic or diagnostic disease-specific biomarkers. In this review, we have discussed pre-analytical and analytical factors that might affect c-miRNA expression and selection of appropriate data normalization strategy by incorporating endogenous reference microRNAs. This review will aid designing of better approaches and protocols for future diagnostic research on hepatic c-microRNAs.

Accuracy and Acceptability of Wrist-Wearable Activity-Tracking Devices: Systematic Review of the Literature.

BACKGROUND: Numerous wrist-wearable devices to measure physical activity are currently available, but there is a need to unify the evidence on how they compare in terms of acceptability and accuracy. OBJECTIVE: The aim of this study is to perform a systematic review of the literature to assess the accuracy and acceptability (willingness to use the device for the task it is designed to support) of wrist-wearable activity trackers. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and SPORTDiscus for studies measuring physical activity in the general population using wrist-wearable activity trackers. We screened articles for inclusion and, for the included studies, reported data on the studies' setting and population, outcome measured, and risk of bias. RESULTS: A total of 65 articles were included in our review. Accuracy was assessed for 14 different outcomes, which can be classified in the following categories: count of specific activities (including step counts), time spent being active, intensity of physical activity (including energy expenditure), heart rate, distance, and speed. Substantial clinical heterogeneity did not allow us to perform a meta-analysis of the results. The outcomes assessed most frequently were step counts, heart rate, and energy expenditure. For step counts, the Fitbit Charge (or the Fitbit Charge HR) had a mean absolute percentage error (MAPE) <25% across 20 studies. For heart rate, the Apple Watch had a MAPE <10% in 2 studies. For energy expenditure, the MAPE was >30% for all the brands, showing poor accuracy across devices. Acceptability was most frequently measured through data availability and wearing time. Data availability was ≥75% for the Fitbit Charge HR, Fitbit Flex 2, and Garmin Vivofit. The wearing time was 89% for both the GENEActiv and Nike FuelBand. CONCLUSIONS: The Fitbit Charge and Fitbit Charge HR were consistently shown to have a good accuracy for step counts and the Apple Watch for measuring heart rate. None of the tested devices proved to be accurate in measuring energy expenditure. Efforts should be made to reduce the heterogeneity among studies.

Dengue NS1 antigen kit shows high sensitivity for detection of recombinant dengue virus-2 NS1 antigen spiked with Aedes aegypti mosquitoes.

Dengue, caused by the dengue virus (DENV) is a significant vector-borne disease. In absence of a specific treatment and vaccine, dengue is becoming a rising threat to public health. Currently, control of dengue mainly focuses on the surveillance of the mosquito vectors. Improved surveillance methods for DENV in mosquito populations would be highly beneficial to the public health. However, current methods of DENV detection in mosquitoes requires specialized equipment and expensive reagents and highly trained personnel. As an alternative, commercially available dengue NS1 antigen ELISA kits could be used for detection of DENV infection in Aedes aegypti mosquitoes. In this study, we explored the utility of commercially available Dengue NS1 antigen kit (J. Mitra & Co. Pvt. Ltd) for the detection of recombinant dengue virus-2 (rDENV-2) NS1 protein and serum of dengue infected patient spiked with Ae. aegypti mosquito pools. The kit was found to be highly sensitive and specific towards detection of all serotypes of DENV. Further, it could detect as low as 750 femto gram rDENV-2 NS1 protein. It was also observed that rDENV-2 NS1 antigen spiked with blood-fed and unfed mosquito pools could be detected. In addition, the kit also detected dengue infected patient serum spiked with Ae. aegypti mosquito pools. Overall, the Dengue NS1 antigen kit displayed high sensitivity towards detection of recombinant as well as serum NS1 protein spiked with Ae. aegypti mosquito pools and could be considered for the dengue virus surveillance after a field evaluation in Ae. aegypti mosquitoes.

Self-reported Wheat Sensitivity in Irritable Bowel Syndrome and Healthy Subjects: Prevalence of Celiac Markers and Response to Wheat-free Diet.

BACKGROUND/AIMS: Most patients with irritable bowel syndrome (IBS) report food-related aggravation of symptoms. Wheat/gluten is one of the most commonly incriminated. We studied the prevalence of self-reported wheat sensitivity in patients with IBS and in a healthy population from a region in India consuming mixed-cereal diets, correlated it with serological and human leukocyte antigen (HLA) markers of celiac disease, and evaluated the response to a wheat-free diet. METHODS: We surveyed 204 patients with IBS and 400 healthy persons for self-reported wheat sensitivity. Testing for IgA anti-tissue transglutaminase and HLA DQ2 or DQ8 was done in individuals who reported wheat sensitivity. Consenting persons with wheat sensitivity were put on wheat-free diet and monitored for symptom change. RESULTS: Twenty-three of 204 patients with IBS (11.3%) and none of the healthy subjects self-reported wheat sensitivity. Of 23 patients, 14 (60.9%) were positive for HLA DQ2 or DQ8 and none for anti-tissue transglutaminase antibody. After 6 weeks on wheat-free diet, all 19 participating patients reported clinical improvement; fewer patients had bloating, diarrhea, constipation, and easy fatigue. CONCLUSIONS: Eleven percent of patients with IBS self-reported wheat sensitivity. None of them had positive celiac serology; 60.9% were positive for HLA DQ2 and DQ8, suggesting a possible genetic basis. All of them improved symptomatically on a wheat-free diet.

Aptamers: An Emerging Tool for Diagnosis and Therapeutics in Tuberculosis.

Tuberculosis (TB) has been plaguing human civilization for centuries, and currently around one-third of the global population is affected with TB. Development of novel intervention tools for early diagnosis and therapeutics against Mycobacterium tuberculosis (M.tb) is the main thrust area in today's scenario. In this direction global efforts were made to use aptamers, the chemical antibodies as tool for TB diagnostics and therapeutics. This review describes the various aptamers introduced for targeting M.tb and highlights the need for development of novel aptamers to selectively target virulent proteins of M.tb for vaccine and anti-TB drugs. The objective of this review is to highlight the diagnostic and therapeutic application of aptamers used for tuberculosis. The discovery of aptamers, SELEX technology, different types of SELEX development processes, DNA and RNA aptamers reported for diseases and pathogenic agents as well have also been described in detail. But the emphasis of this review is on the development of aptamers which can block the function of virulent mycobacterial components for developing newer TB vaccine candidates and/or drug targets. Aptamers designed to target M.tb cell wall proteins, virulent factors, secretory proteins, or combination could orchestrate advanced diagnosis and therapeutic measures for tuberculosis.

Management of Helicobacter pylori infection: The Bhubaneswar Consensus Report of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.

Is the rise in Crohn's disease in India accompanied by a fall in intestinal tuberculosis? A single-center experience.

INTRODUCTION: The relationship between the incidence of intestinal tuberculosis (TB) and Crohn's disease (CD) is interesting, especially considering the striking similarity between the two conditions. Some studies from Asian populations suggested that the incidence of intestinal TB decreases when there is an increase in CD. AIM: To compare the incidence trend between intestinal TB and CD over 15 years. METHODS: Medical records of patients seen in the Division of Gastroenterology over 15 years (2005-2019) were reviewed. CD was diagnosed according to the Copenhagen criteria. Intestinal TB was diagnosed in the appropriate clinical situation if any one or more of the following was present: (1) positive TB MGIT culture; (2) positive Gene Xpert for TB; (3) suggestive histologic findings, with positive tissue acid-fast bacillus (AFB) on smear or with sustained response to anti-TB therapy. The incidence time trend of patients with CD and intestinal TB diagnosis was then studied year-wise. RESULTS: 632 medical case records were accessed; 60 patients were excluded due to inadequate data or not fulfilling diagnostic criteria. The 572 patients included 224 with intestinal TB (median age 37 years, IQR 22; 125 [56%] females) and 348 with CD (median age 40 years, IQR 25; 159 [46%] females [p < 0.02 as compared to TB]). Thus, more patients with CD were seen during the study period, but there was no correlation between the incidence of the two conditions (r = 0.318; p = 0.25). CONCLUSION: In Indian patients in a single private-sector center, there was no inverse correlation between the incidence of intestinal TB and CD over 15 years.