Assessment of the 2021 AASLD Practice Guidance for Albumin Infusion in Elective Therapeutic Paracentesis: A Regression Discontinuity Design.

INTRODUCTION: The 2021 American Association for the Study of Liver Disease (AASLD) Practice Guidance recommends albumin infusion when removing ≥5 L of ascites to prevent post-paracentesis circulatory dysfunction. However, the optimal criteria and scenarios for initiating albumin infusion subsequent to therapeutic paracentesis (TP) have been subject to limited scientific inquiry. METHODS: We conducted a retrospective cohort study at a US academic healthcare center. Participants received elective, outpatient TP between July 2019 and December 2022. Patients with spontaneous bacterial peritonitis, post-TP clinical adjustments, and/or hospitalization were excluded. The institution strictly followed the AASLD Guidance. We used a sharp regression discontinuity (RD) design to estimate the effect of albumin infusion at the AASLD Guidance-recommended cutoff of 5 L on serum creatinine and sodium trajectory after TP. RESULTS: Over the study period, 1,457 elective TPs were performed on 235 unique patients. Albumin infusion at the threshold of 5 L of ascites removal reduced serum creatinine levels by 0.046 mg/dL/d (95% confidence interval 0.003-0.116, P = 0.037) and increased serum sodium levels by 0.35 mEq/L/d (95% confidence interval 0.15-0.55, P = 0.001) compared with those who did not receive albumin infusion. The RD plots indicated worsened serum creatine/sodium levels after draining 3 L of fluid, approaching levels similar to or worse than with albumin infusion at 5 L or more. DISCUSSION: Our RD models supported the 2021 AASLD Guidance with robust estimation of causal effect sizes at the cutoff level of 5 L. Nevertheless, the findings also highlight the need to further evaluate the efficacy of albumin infusion in patients who undergo elective TP and have 3-5 L of ascites removed.

A Minority of Childhood Disorders of Gut-Brain Interaction Persist Into Adulthood: A Risk-Factor Analysis.

INTRODUCTION: Disorders of gut-brain interaction (DGBIs) may originate in childhood. There are currently limited data on persistence of DGBI into adulthood and risk factors for persistence. Furthermore, there are no data on this question from general practice, where the majority of DGBIs are diagnosed and managed. This study documents the proportion of childhood-diagnosed DGBIs that persisted into adulthood and what factors were associated with persistence. METHODS: General practice records were obtained for more than 60,000 patients whose medical record spanned both childhood and adulthood years. Patients with diagnosed organic gastrointestinal disorder were excluded. Medical records were also interrogated for potential risk factors. RESULTS: Eleven percent of patients with irritable bowel syndrome (IBS) and 20% of patients with functional dyspepsia (FD) diagnosed in childhood had repeat diagnoses of the same condition in adulthood. Female sex (odds ratio [OR] 2.02) was associated with persistence for IBS, while a childhood diagnosis of gastritis (OR 0.46) was risk-protective. Childhood non-steroidal anti-inflammatory drug use (OR 1.31, 95% confidence interval [CI] 1.09-1.56) was a risk factor for persistence in IBS. For FD, a childhood diagnosis of asthma (OR 1.30, 95% CI 1.00-1.70) was a risk factor, as was anxiety for both IBS (OR 1.24, 95% CI 1.00-1.54) and FD (OR 1.48 95% CI 1.11-1.97) with a similar finding for depression for IBS (OR 1.34, 95% CI 1.11-1.62) and FD (OR 1.88 95% CI 1.47-2.42). DISCUSSION: Childhood DGBIs persist into adulthood in 10%-20% of patients, suggesting that management monitoring should continue into adulthood. Those diagnosed with anxiety or mood disorders in childhood should receive particular attention, and prescription of non-steroidal anti-inflammatory drugs in children should be made judiciously.

Defecation Symptoms in Relation to Stool Consistency Significantly Reflect the Dyssynergic Pattern in High-resolution Anorectal Manometry in Constipated Patients.

GOALS: To evaluate the usefulness of a 2-week patient-completed bowel habit and symptom diary as a screening tool for disordered rectoanal coordination (DRC). BACKGROUND: DRC is an important subgroup of chronic constipation that benefits from biofeedback treatment. Diagnosis of DRC requires a dyssynergic pattern (DP) of attempted defecation in high-resolution anorectal manometry (HRAM) and at least 1 other positive standardized examination, such as the balloon expulsion test or defecography. However, HRAM is generally limited to tertiary gastroenterology centres and finding tools for selecting patients for referral for further investigations would be of clinical value. STUDY: Retrospective data from HRAM and a 2-week patient-completed bowel habit and symptom diary from 99 chronically constipated patients were analyzed. RESULTS: Fifty-seven percent of the patients had a DP pattern during HRAM. In the DP group, 76% of bowel movements with loose or normal stool resulted in a sense of incomplete evacuation compared with 55% of the non-DP group ( P =0.004). Straining and sensation of incomplete evacuation with the loose stool were significantly more common in the DP group ( P =0.032). Hard stool was a discriminator for non-DP ( P =0.044). Multiple logistic regression including incomplete evacuation and normal stool predicted DP with a sensitivity of 82% and a specificity of 50%. CONCLUSIONS: The sensation of incomplete evacuation with loose or normal stool could be a potential discriminator in favor of DP in chronically constipated patients. The bowel habit and symptom diary may be a useful tool for stratifying constipated patients for further investigation of suspected DRC.

Defecation symptoms in primary health care patients with irritable bowel syndrome.

BACKGROUND: The objectives of the present study were to (a) measure the prevalence of defecation symptoms in IBS, (b) investigate the relationship between stool consistency and defecation symptoms in IBS, and (c) investigate the association of defecation symptoms with health-related quality of life (HRQL) and self-reported stress in patients with IBS cared for in a primary health care setting. METHODS: Ten primary health care centres joined the study. 282 patients with IBS as well as 372 non-IBS controls filled in gastrointestinal symptom diaries prospectively for two weeks as well as the Perceived Stress Scale-14 (PSS14) and the EuroQol barometer to measure perceived stress and HRQL, respectively. RESULTS: Incomplete evacuation was present in 51% vs. 21% of the stools among the IBS patients and the non-IBS controls, respectively. The need to strain during defecation was existing in 41% vs. 33% of the stools for the IBS patients and the non-IBS controls, respectively. Urgency was experienced in 37% of the stools in the IBS patients compared with 18% of the stools in the non-IBS controls. Patients with IBS experienced in a significant higher degree of overlapping symptoms per stool (p < 0.001 to p = 0.007). The occurrence of all defecation symptoms in the same patient was related to decreased HRQL, and increased stress (p = 0.001 to p < 0.001). CONCLUSIONS: An overlap between IBS and symptoms from the anorectal region related to defecation was found in a primary health care population. Defecation symptoms are very common in primary care IBS-patients, it co-occurs with increased self-perceived stress, and decreased HRQL.

Prevalence of small intestinal bacterial overgrowth in intestinal failure syndrome: A systematic review and meta-analysis.

BACKGROUND AND AIM: Patients with intestinal failure (IF) have abnormal intestinal anatomy, secretion, and dysmotility, which impairs intestinal homeostatic mechanisms and may lead to small intestinal bacterial overgrowth (SIBO). We conducted a systematic review and meta-analysis to determine the prevalence of SIBO in patients with IF and to identify risk factors for SIBO. METHODS: MEDLINE (PubMed) and Embase electronic databases were searched from inception to December 2023 for studies that reported the prevalence of SIBO in IF. The prevalence rates, odds ratio (OR), and 95% confidence intervals of SIBO in IF and the risk factors for SIBO in IF were calculated using random effects model. RESULTS: Final dataset included nine studies reporting on 407 patients with IF. The prevalence of SIBO in IF was 57.5% (95% CI 44.6-69.4), with substantial heterogeneity in this analysis (I2 = 80.9, P = 0.0001). SIBO prevalence was sixfold higher in patients with IF who received parenteral nutrition (PN) compared with IF patients not on PN (OR = 6.0, 95% CI 3.0-11.9, P = 0.0001). Overall, the prevalence of SIBO in patients with IF using PPI/acid-suppressing agents (72.0%, 95% CI 57.5-83.8) was numerically higher compared with IF patients not using these agents (47.6%, 95% CI 25.7-70.2). CONCLUSIONS: This systematic review and meta-analysis suggests that there is an increased risk of SIBO in patients with IF and that PN, and potentially, the use of PPI/acid-suppressing agents is risk factors for SIBO development in patients with IF. However, the quality of evidence is low and can be attributed to lack of case-control studies and clinical heterogeneity seen in the studies.

Healthcare Utilization Patterns: Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Gastroesophageal Reflux Disease.

BACKGROUND: Limited information is available about patterns of healthcare utilization for prevalent gastrointestinal conditions and their link to symptom burden. AIM: To identify patterns of healthcare utilization among outpatients with highly prevalent gastrointestinal conditions and define the link between healthcare utilization, symptom burden, and disease group. METHODS: We randomly selected patients from the gastroenterology outpatient clinic at Princess Alexandra Hospital who had chronic gastrointestinal conditions such as constipation-predominant irritable bowel syndrome (IBS-C, n = 101), diarrhea-predominant IBS (IBS-D, n = 101), mixed IBS (n = 103), inflammatory bowel disease with acute flare (n = 113), IBD in remission (n = 103), and gastroesophageal reflux disease (n = 102). All had presented at least 12 months before and had a 12-month follow-up after the index consultation. Healthcare utilization data were obtained from state-wide electronic medical records over a 24-month period. Intensity of gastrointestinal symptoms was measured using the validated Structured Assessment of Gastrointestinal Symptoms (SAGIS) Scale. Latent class analyses (LCA) based on healthcare utilization were used to identify distinct patterns of healthcare utilization among these patients. RESULTS: LCA revealed four distinct healthcare utilization patterns across all diagnostic groups: Group A: Emergency department utilizers, Group B: Outpatient focused care utilizers, Group C: Inpatient care utilizers and Group D: Inpatient care and emergency department utilizers. LCA groups with high emergency utilization were characterized by high gastrointestinal symptom burden at index consultation regardless of condition (Mean (standard deviation)) SAGIS score Group A: 24.63 (± 14.11), Group B: 19.18 (± 15.77), Group C: 22.48 (± 17.42), and Group D: 17.59 (± 13.74, p < 0.05). CONCLUSION: Distinct healthcare utilization patterns across highly prevalent gastrointestinal conditions exist. Symptom severity rather than diagnosis, likely reflecting unmet clinical need, defines healthcare utilization.

The association between physical intervention use and treatment outcomes in patients participating in an online and psychologically informed pain management program.

BACKGROUND: The availability of multidisciplinary care for the management of chronic pain is uncommon outside specialist clinics. The current study aims to determine the physical intervention use of patients participating in an online psychological pain management program and whether exposure to physical interventions in these patients alters treatment outcomes compared to patients who do not access physical interventions. METHODS: Data were obtained from two previously published randomised control trials of an online psychological pain management program. Physical intervention exposure (category: None, 1-3, 4+ sessions) was assessed at baseline, post-treatment and at 3-month follow-up. Primary outcomes included depression, anxiety, pain intensity and pain-related disability. Generalised estimating equation models were used to compare treatment outcomes between those with different physical intervention frequencies and period of exposure. We assessed whether changes in primary outcomes differed (moderated) depending on the period and category of physical intervention exposure. RESULTS: N = 1,074 patients completed the baseline questionnaire across both RCTs, of whom 470 (44%) reported physical intervention use at baseline, 383 (38%) at post-treatment and 363 (42%) at 3-month follow-up. On average, there were moderate-large reductions from baseline to post-treatment with respect to all outcomes (Cohen's d = 0.36-0.82). In all outcomes, the interaction of time by physical intervention exposure was statistically non-significant. CONCLUSION: A substantial proportion of patients who participated in a psychologically informed pain management program were establishing, continuing, or stopping additional physical interventions. The frequency and period of exposure to physical interventions did not appear moderate treatment outcomes.

Factors Associated With Placebo Treatment Response in Functional Dyspepsia Clinical Trials.

INTRODUCTION: Controlling for potential placebo effects is an important aspect of gaining an accurate estimate of how much the therapy alone changes patient symptoms or other end points. When the placebo effect is large, this can lead to only a small fraction of changes seen in the active therapy group being attributed to the therapy itself. This problem has been well studied in some disorders of brain-gut interaction but not in functional dyspepsia where placebo response rates of 40% and higher have been reported. Understanding risk factors for placebo response might lead to changes in trial design that could reduce the magnitude of the problem. This study sought to identify risk factors for the placebo effect in a functional dyspepsia clinical trial with a longer-term aim of suggesting trial design changes that might minimize the problem. METHODS: A secondary analysis of the clinical trial data was undertaken using 2 arms deemed to involve placebo therapy. Potential predictors were drawn from a wide range of patient characteristics including psychological, clinical, and physiological features. RESULTS: Predictors of a stronger placebo effect on the gastrointestinal symptom rating scale included higher functional dyspepsia symptom burden at baseline ( b = -0.101), coexisting irritable bowel syndrome ( b = -0.436), and higher scores on the Nepean Dyspepsia Index eat/drink domain (-0.005). Baseline symptom burden and coexisting irritable bowel syndrome were found to be independent placebo predictors, explaining 13% of the variance in change in gastrointestinal symptom rating scale. Anxiety, childhood sexual abuse, sleep amount, and frequent abdominal pain were also found to be predictors of change in individual symptom scores. DISCUSSION: The findings of this study yield actionable insights into trial methodology that may help to reduce the magnitude of the placebo effect in future functional dyspepsia treatment trials.

Upper GI endoscopy in subjects with positive fecal occult blood test undergoing colonoscopy: systematic review and meta-analysis.

BACKGROUND AND AIMS: The role of gastroscopy to investigate the upper GI (UGI) tract in subjects with a positive fecal occult blood test (FOBT+) result is controversial. We conducted a systematic review and meta-analysis, which aimed to determine the prevalence of UGI lesions in FOBT+ subjects. METHODS: Databases were searched until March 31, 2022 for studies reporting UGI lesions in FOBT+ subjects undergoing colonoscopy and gastroscopy. Pooled prevalence rates of UGI cancers and clinically significant lesions (CSLs; lesions potentially explaining occult blood loss), odds ratio (OR), and 95% confidence intervals (CIs) were calculated. RESULTS: We included 21 studies with 6993 FOBT+ subjects. Pooled prevalence of UGI cancers was .8% (95% CI, .4-1.6) and UGI CSLs was 30.4% (95% CI, 20.7-42.2), and that of colonic cancers and CSLs was 3.3% (95% CI, 1.8-6.0) and 31.9% (95% CI, 23.9-41.1), respectively. There was no significant difference in the prevalence of UGI CSL and UGI cancers in FOBT+ subjects with/without colonic pathology (ORs of 1.2 [95% CI, .9-1.6; P = .137] and 1.6 [95% CI, .5-5.5; P = .460]). Anemia in FOBT+ subjects was associated with UGI cancers (OR, 6.3; 95% CI, 1.3-31.5; P = .025) and UGI CSLs (OR, 4.3; 95% CI, 2.2-8.4; P = .0001). GI symptoms were not associated with UGI CSLs (OR, 1.3; 95% CI, .6-2.8; P = .511). CONCLUSIONS: There is an appreciable prevalence of UGI cancers and other CSLs in FOBT+ subjects. Anemia but not symptoms or colonic pathology are linked to UGI lesions. Although the data suggest that same-day gastroscopy in FOBT+ subjects undergoing colonoscopy yields approximately 25% more malignancies as colonoscopy alone, prospective data are required to determine the cost-efficacy of dual endoscopy as a standard of care for all FOBT+ subjects.

Flatus Incontinence and Fecal Incontinence: A Case-Control Study.

BACKGROUND: Incontinence to gas can be a troublesome symptom impacting quality of life for patients even in the absence of fecal incontinence. Whether isolated flatus incontinence represents part of the spectrum of true fecal incontinence or a separate condition with a different pathophysiology remains unclear. OBJECTIVE: This study aimed to evaluate the clinical features and anorectal physiology in women presenting with severe isolated flatus incontinence compared to women with fecal incontinence and healthy asymptomatic women. DESIGN: This was a retrospective case-control study of prospectively collected data. SETTINGS: Data from participants were obtained from a single tertiary Neurogastroenterology Unit in Sydney, Australia. PATIENTS: Data from 34 patients with severe isolated flatus incontinence, 127 women with fecal incontinence' and 44 healthy women were analyzed. MAIN OUTCOME MEASURES: The primary outcomes were clinical (including demographic, obstetric, and symptom variables) and physiological differences across the 3 groups. RESULTS: Patients with flatus incontinence were significantly younger (mean 39 versus 63 years; p = 0.0001), had a shorter history of experiencing their symptoms ( p = 0.0001), and had harder stool form than patients with fecal incontinence ( p = 0.02). Those with flatus incontinence had an adverse obstetric history and impaired anorectal physiology (motor and sensory, specifically rectal hypersensitivity) but to a lesser extent than patients with fecal incontinence. LIMITATIONS: This study was limited by its retrospective design and modest sample size. CONCLUSIONS: Anorectal physiology was impaired in patients with flatus incontinence compared to healthy controls, but to a lesser extent than in those with fecal incontinence, raising the possibility that flatus incontinence could be a precursor to fecal incontinence. As clinical and physiological findings are different from healthy controls (including the presence of visceral hypersensitivity), isolated flatus incontinence should be considered a distinct clinical entity (like other functional GI disorders), or possibly part of an incontinence spectrum rather than purely a normal phenomenon. See Video Abstract at http://links.lww.com/DCR/B946 . INCONTINENCIA DE FLATOS E INCONTINENCIA FECAL UN ESTUDIO DE CASOS Y CONTROLES: ANTECEDENTES:La incontinencia de gases puede ser un síntoma molesto que afecta la calidad de vida de los pacientes incluso en ausencia de incontinencia fecal. Aún no está claro si la incontinencia de flatos aislada representa parte del espectro de la incontinencia fecal verdadera o una condición separada con una fisiopatología poco clara.OBJETIVO:Evaluar las características clínicas y la fisiología anorrectal en mujeres que presentan incontinencia grave aislada de flatos, en comparación con la incontinencia fecal y mujeres sanas asintomáticas.DISEÑO:Este fue un estudio retrospectivo de casos y controles de datos recolectados prospectivamente.AJUSTE:Los datos de los participantes se obtuvieron de una sola Unidad de Neurogastroenterología terciaria en Sydney, Australia.PACIENTES:Se analizaron los datos de 34 pacientes con incontinencia grave aislada de flatos, junto con 127 mujeres con incontinencia fecal y 44 mujeres sanas.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron clínicos (incluidas las variables demográficas, obstétricas y de síntomas), así como las diferencias fisiológicas entre los tres grupos.RESULTADOS:Los pacientes con incontinencia de flatos eran significativamente más jóvenes (media de 39 años frente a 63 años, p = 0,0001), tenían un historial más corto de experimentar sus síntomas (p = 0,0001) y tenían heces más duras que los pacientes con incontinencia fecal (p = 0,02). Aquellos con incontinencia de flatos tenían antecedentes obstétricos adversos y fisiología anorrectal alterada (motora y sensorial, específicamente hipersensibilidad rectal); aunque en menor medida que las pacientes con incontinencia fecal.LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo y tamaño de muestra modesto.CONCLUSIONES:La fisiología anorrectal se vio afectada en las pacientes con incontinencia de flatos en comparación con las controles sanos, pero en menor medida que en aquellas con incontinencia fecal, lo que plantea la posibilidad de que la incontinencia de flatos pueda ser un precursor de la incontinencia fecal. Dado que los hallazgos clínicos y fisiológicos son diferentes a los de los controles sanos (incluida la presencia de hipersensibilidad visceral), la incontinencia de flatos aislada debe considerarse como una entidad clínica distinta (al igual que otros trastornos gastrointestinales funcionales), o posiblemente como parte de un espectro de incontinencia en lugar de un trastorno puramente a un fenómeno normal. Consulte Video Resumen en http://links.lww.com/DCR/B946 . (Traducción-Dr Yolanda Colorado ).

Development and Validation of a Patient-Reported Experience Measure for Gastrointestinal Endoscopy: The Comprehensive Endoscopy Satisfaction Tool (CEST).

GOALS: We aimed to develop and validate a patient-reported experience measure for gastrointestinal (GI) endoscopy, the Comprehensive Endoscopy Satisfaction Tool that captures relevant domains that influence the patient's experience and identify factors that shape satisfaction. BACKGROUND: Patient-reported experience measures are used to capture specific quality aspects of health care services. GI endoscopic services are high-volume services, and there is a lack of specific, validated instruments to capture various domains that shape the patients' experience with routine clinical endoscopic services. STUDY: After an environmental scan and structured literature review, focus groups with patients were conducted to identify relevant factors influencing the patient experience with GI endoscopic services. After an initial validation in 101 patients undergoing routine GI endoscopies, the instrument was tested in 7800 patients. In addition, the influence of sociodemographic factors on global satisfaction was explored. RESULTS: The final version included 26 specific items plus 4 global ratings for preprocedure, experience on day of procedure, postprocedure care, and infrastructure. In addition, a global rating of the overall experience was included. Patient satisfaction was significantly higher in older patients (P<0.001) but not influenced by gender, nationality, marital status, education, or employment status. Interestingly, during periods of coronavirus disease-19-related service interruptions, the Net Promoter Score was significantly reduced (P<0.0001) providing evidence for the responsiveness of the instrument. CONCLUSIONS: The Comprehensive Endoscopy Satisfaction Tool is a valid measure for the patient experience with the various components of endoscopic services, allows for the identification of domains that impact on the patient experience and is a practical tool to compare patient satisfaction over time and across facilities.

Outcomes Associated With Rural Emergency Department Provider-to-Provider Telehealth for Sepsis Care: A Multicenter Cohort Study.

STUDY OBJECTIVE: To test the hypothesis that provider-to-provider tele-emergency department care is associated with more 28-day hospital-free days and improved Surviving Sepsis Campaign (SSC) guideline adherence in rural emergency departments (EDs). METHODS: Multicenter (n=23), propensity-matched, cohort study using medical records of patients with sepsis from rural hospitals in an established, on-demand, rural video tele-ED network in the upper Midwest between August 2016 and June 2019. The primary outcome was 28-day hospital-free days, with secondary outcomes of 28-day inhospital mortality and SSC guideline adherence. RESULTS: A total of 1,191 patients were included in the analysis, with tele-ED used for 326 (27%). Tele-ED cases were more likely to be transferred to another hospital (88% versus 8%, difference 79%, 95% confidence interval [CI] 75% to 83%). After matching and regression adjustment, tele-ED cases did not have more 28-day hospital-free days (difference 0.07 days more for tele-ED, 95% CI -0.04 to 0.17) or 28-day inhospital mortality (adjusted odds ratio [aOR] 0.51, 95% CI 0.16 to 1.60). Adherence with both the SSC 3-hour bundle (aOR 0.59, 95% CI 0.28 to 1.22) and complete bundle (aOR 0.45, 95% CI 0.02 to 11.60) were similar. An a priori-defined subgroup of patients treated by advanced practice providers suggested that the mortality was lower in the cohort with tele-ED use (aOR 0.11, 95% CI 0.02 to 0.73) despite no significant difference in complete SSC bundle adherence (aOR 2.88, 95% CI 0.52 to 15.86). CONCLUSION: Rural emergency department patients treated with provider-to-provider tele-ED care in a mature network appear to have similar clinical outcomes to those treated without.

Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment.

BACKGROUND: Gestational exposure to polychlorinated biphenyls (PCBs) has been associated with elevated risk for neurodevelopmental disorders. Placental epigenetics may serve as a potential mechanism of risk or marker of altered placental function. Prior studies have associated differential placental DNA methylation with maternal PCB exposure or with increased risk of autism spectrum disorder (ASD). However, sequencing-based placental methylomes have not previously been tested for simultaneous associations with maternal PCB levels and child neurodevelopmental outcomes. OBJECTIVES: We aimed to identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes in the high-risk ASD MARBLES cohort. METHODS: We measured 209 PCB congeners in 104 maternal serum samples collected at delivery. We identified networks of DNA methylation from 147 placenta samples using the Comethyl R package, which performs weighted gene correlation network analysis for whole genome bisulfite sequencing data. We tested placental DNA methylation modules for association with maternal serum PCB levels, child neurodevelopment, and other participant traits. RESULTS: PCBs 153 + 168, 170, 180 + 193, and 187 were detected in over 50% of maternal serum samples and were highly correlated with one another. Consistent with previous findings, maternal age was the strongest predictor of serum PCB levels, alongside year of sample collection, pre-pregnancy BMI, and polyunsaturated fatty acid levels. Twenty seven modules of placental DNA methylation were identified, including five which significantly correlated with one or more PCBs, and four which correlated with child neurodevelopment. Two modules associated with maternal PCB levels as well as child neurodevelopment, and mapped to CSMD1 and AUTS2, genes previously implicated in ASD and identified as differentially methylated regions in mouse brain and placenta following gestational PCB exposure. CONCLUSIONS: Placental DNA co-methylation modules were associated with maternal PCBs and child neurodevelopment. Methylation of CSMD1 and AUTS2 could be markers of altered placental function and/or ASD risk following maternal PCB exposure.

Telehealth in remote Australia: a supplementary tool or an alternative model of care replacing face-to-face consultations?

BACKGROUND: The COVID-19 pandemic increased the use of telehealth consultations by telephone and video around the world. While telehealth can improve access to primary health care, there are significant gaps in our understanding about how, when and to what extent telehealth should be used. This paper explores the perspectives of health care staff on the key elements relating to the effective use of telehealth for patients living in remote Australia. METHODS: Between February 2020 and October 2021, interviews and discussion groups were conducted with 248 clinic staff from 20 different remote communities across northern Australia. Interview coding followed an inductive approach. Thematic analysis was used to group codes into common themes. RESULTS: Reduced need to travel for telehealth consultations was perceived to benefit both health providers and patients. Telehealth functioned best when there was a pre-established relationship between the patient and the health care provider and with patients who had good knowledge of their personal health, spoke English and had access to and familiarity with digital technology. On the other hand, telehealth was thought to be resource intensive, increasing remote clinic staff workload as most patients needed clinic staff to facilitate the telehealth session and complete background administrative work to support the consultation and an interpreter for translation services. Clinic staff universally emphasised that telehealth is a useful supplementary tool, and not a stand-alone service model replacing face-to-face interactions. CONCLUSION: Telehealth has the potential to improve access to healthcare in remote areas if complemented with adequate face-to-face services. Careful workforce planning is required while introducing telehealth into clinics that already face high staff shortages. Digital infrastructure with reliable internet connections with sufficient speed and latency need to be available at affordable prices in remote communities to make full use of telehealth consultations. Training and employment of local Aboriginal staff as digital navigators could ensure a culturally safe clinical environment for telehealth consultations and promote the effective use of telehealth services among community members.

Duodenal Eosinophils and Mast Cells in Functional Dyspepsia: A Systematic Review and Meta-Analysis of Case-Control Studies.

BACKGROUND & AIMS: This study explored the link between duodenal eosinophils and mast cells in patients with functional dyspepsia (FD). METHODS: MEDLINE (PubMed) and Embase electronic databases were searched until June 2021 for case-control studies reporting duodenal eosinophils and mast cells in FD. Pooled standardized mean difference (SMD), odds ratio, and 95% CIs of duodenal eosinophils and mast cells in FD patients and controls were calculated, using a random-effects model. RESULTS: Twenty-two case-control studies with 1108 FD patients and 893 controls were identified. Duodenal eosinophils (SMD, 1.29; 95% CI, 0.85-1.73; P = .0001) and mast cells (SMD, 2.11; 95% CI, 1.14-3.07; P = .0001) were increased in FD patients compared with controls. Substantial heterogeneity was found (I2 = 93.61, P = .0001; and I2 = 96.69, P = .0001, respectively) and visual inspection of funnel plots confirmed publication bias. Degranulation of duodenal eosinophils was significantly higher in FD patients compared with controls (odds ratio, 3.78; 95% CI, 6.76-4.48; P = .0001), without statistically significant heterogeneity. We conducted a sensitivity analysis for duodenal eosinophils, by including only high-quality studies, and the results remained unchanged (SMD, 1.73; 95% CI, 1.06-2.40; P = .0001), with substantial heterogeneity. Postinfectious FD patients had increased duodenal eosinophils compared with controls (SMD, 3.91; 95% CI, 1.32-6.51; P = .001) and FD patients without any history of infection (SMD, 1.42; 95% CI, 0.88-1.96; P = .001). Helicobacter pylori-negative FD patients had significantly higher duodenal eosinophils compared with controls (SMD, 3.98; 95% CI, 2.13-5.84; P = .0001), with substantial heterogeneity. No significant difference in duodenal eosinophils was seen according to FD subtypes. CONCLUSIONS: This meta-analysis suggests a link between duodenal microinflammation and FD. However, the quality of evidence is very low, largely owing to the unexplained heterogeneity and serious risk of publication bias in all comparative analyses. Thus, causality remains uncertain and further studies are required.

Effects of Adult Medicaid Dental Benefits Elimination on Child Dental Care Use.

OBJECTIVE: The objective of this study was to examine the effect of adult dental benefit cuts on child dental use in Washington state Medicaid and determine if cuts affect child demographic subgroups differentially. RESEARCH DESIGN: The study used an interrupted time-series methodology to measure differences in child dental use after adult dental benefit elimination and reinstatement. Monthly data came from Washington state Medicaid enrollee and dental claim files from January 2008 to December 2015. SUBJECTS: Medicaid-enrolled children with at least one Medicaid-enrolled adult in the same household were the intervention group, and Medicaid-enrolled children without a Medicaid-enrolled adult in the same household were the control group. MEASURES: The outcome was the monthly proportion of Medicaid-enrolled children with a dental examination per 10,000 Medicaid-enrolled children. RESULTS: After adult dental benefits elimination, dental examinations among children with Medicaid-enrolled adults in the same household gradually decreased, corresponding to 65 fewer dental examinations per 10,000 children per year (5.4 fewer dental examinations per 10,000 children per month; 95% confidence interval: -7.7, -3.1; P =0.006). Adult dental benefits had no effect on dental examination for children without a Medicaid-enrolled adult in the same household. Dental examinations for children with a Medicaid-enrolled adult in the same household continued to gradually decrease after adult benefits reinstatement. Children younger than age 6 were the most adversely impacted by changes to adult Medicaid dental benefits. CONCLUSION: Policymakers should consider the spillover effects and ethical considerations of eliminating adult Medicaid dental benefits on children's access to dental care.

The Chronic Conditions Course: A Randomised Controlled Trial of an Internet-Delivered Transdiagnostic Psychological Intervention for People with Chronic Health Conditions.

INTRODUCTION: Psychological adjustment to chronic health conditions is important, as poor adjustment predicts a range of adverse medical and psychosocial outcomes. Psychological treatments demonstrate efficacy for people with chronic health conditions, but existing research takes a disorder-specific approach and they are predominately delivered in face-to-face contexts. The internet and remotely delivered treatments have the potential to overcome barriers to accessing traditional face-to-face treatment. OBJECTIVE: The current study examined the efficacy and acceptability of an internet-delivered transdiagnostic psychological intervention to promote adjustment to illness, based on cognitive behaviour therapy principles. METHODS: In a two-arm randomised controlled trial, participants (n = 676) were randomly allocated to the 8-week intervention or a waitlist control. Treatment included five core lessons, homework tasks, additional resources, and weekly contact with a psychologist. Primary outcomes included depression, anxiety, and disability, assessed at pre-treatment, post-treatment, 3-month follow-up, and 12-month follow-up. RESULTS: The treatment group reported significantly greater improvements in depression (between-groups d = 0.47), anxiety (d = 0.32), and disability (d = 0.17) at post-treatment (all ps <0.001). Improvements were sustained over the 3-month and 12-month follow-ups. High treatment completion rates (69%) and levels of satisfaction (86%) were reported by participants in treatment. The intervention required a mean clinician time of 56.70 min per participant. CONCLUSIONS: The findings provide preliminary and tentative support for the potential of internet-delivered transdiagnostic interventions to promote adjustment to chronic health conditions. Further research using robust control groups, and exploring the generalisability of findings, is needed before firm conclusions can be drawn.

Links between celiac disease and small intestinal bacterial overgrowth: A systematic review and meta-analysis.

BACKGROUND AND AIM: Symptoms of small intestinal bacterial overgrowth (SIBO) and celiac disease (CeD) often overlap, and studies suggest a link between SIBO and CeD. We thus conducted a systematic review and meta-analysis to compare SIBO prevalence in CeD patients and controls and assessed effects of antimicrobial therapy on gastrointestinal symptoms in SIBO positive CeD patients. METHODS: Electronic databases were searched until February 2022 for studies reporting SIBO prevalence in CeD. Prevalence rates, odds ratio (OR), and 95% confidence intervals (CI) of SIBO in CeD and controls were calculated. RESULTS: We included 14 studies, with 742 CeD patients and 178 controls. The pooled prevalence of SIBO in CeD was 18.3% (95% CI: 11.4-28.1), with substantial heterogeneity. Including case-control studies with healthy controls, SIBO prevalence in CeD patients was significantly increased (OR 5.1, 95% CI: 2.1-12.4, P = 0.0001), with minimal heterogeneity. Utilizing breath tests, SIBO prevalence in CeD patients was 20.8% (95% CI: 11.9-33.7), almost two-fold higher compared with culture-based methods at 12.6% (95% CI: 5.1-28.0), with substantial heterogeneity in both analyses. SIBO prevalence in CeD patients nonresponsive to a gluten free diet (GFD) was not statistically higher as compared with those responsive to GFD (OR 1.5, 95% CI: 0.4-5.0, P = 0.511). Antibiotic therapy of SIBO positive CeD patients resulted in improvement in gastrointestinal symptoms in 95.6% (95% CI: 78.0-99.9) and normalization of breath tests. CONCLUSIONS: This study suggests a link between SIBO and CeD. While SIBO could explain nonresponse to a GFD in CeD, SIBO prevalence is not statistically higher in CeD patients non-responsive to GFD. The overall quality of the evidence is low, mainly due to substantial "clinical heterogeneity" and the limited sensitivity/specificity of the available diagnostic tests.

Effectiveness and Safety of Ustekinumab in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Ustekinumab, an interleukin-12 and interleukin-23 antagonist, is licensed for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) after the phase III trial programs demonstrated efficacy over placebo. However, these findings may not be directly transferable to the real-world due to the stringent inclusion criteria of clinical trials. METHODS: We conducted a systematic review and meta-analysis of the safety and effectiveness of ustekinumab in inflammatory bowel disease (IBD). A systematic literature search was conducted via Medline and Embase from inception to April 21, 2020. Observational studies assessing ustekinumab's safety and effectiveness by reporting response, remission and/or adverse events (AE) in either CD or UC were included. Two reviewers independently assessed risk of bias and extracted study data. Random-effects meta-analysis was performed to pool rates of clinical response, remission, and safety data. RESULTS: Following deduplication, 2147 records were identified of which 41 studies (38 CD, 3 UC) comprising 4400 patients were included for quantitative analysis. Pooled clinical remission rates for CD were 34% (95% CI, 26%-42%) following induction and 31% (95% CI, 25%-38%) at one year. For UC, post-induction clinical remission rates were 39% (95% CI, 23%-56%). Serious AEs were reported in 5.6% of patients. Pregnancy outcomes were similar to the general population. One-third of patients with active baseline perianal disease responded or had fistula healing with ustekinumab. CONCLUSIONS: In the most comprehensive systematic review and meta-analysis to date, and the first to include UC, ustekinumab was shown to be effective and safe in the real-world treatment of IBD.

Concomitant Irritable Bowel Syndrome Does Not Influence the Response to Antimicrobial Therapy in Patients with Functional Dyspepsia.

BACKGROUND AND AIMS: Antimicrobial therapy improves symptoms in patients with irritable bowel syndrome (IBS), but the efficacy in functional dyspepsia (FD) is largely unknown. While FD and IBS frequently overlap, it is unknown if concomitant IBS in FD alters the response to antimicrobial therapy in FD. Thus, we aimed to assess and compare the effect of antimicrobial therapy on visceral sensory function and symptom improvement in FD patients with and without IBS. METHODS: Adult patients with FD with or without IBS received rifaximin 550 mg BD for 10 days, followed by a 6-week follow-up period. The total gastrointestinal symptom score as measured by the SAGIS (Structured Assessment of Gastrointestinal Symptoms) questionnaire and subscores (dyspepsia, diarrhea, and constipation), symptom response to a standardized nutrient challenge and normalization of the glucose breath tests were measured. RESULTS: Twenty-one consecutive adult patients with FD and 14/21 with concomitant IBS were recruited. Treatment with rifaximin resulted in a significant (p = 0.017) improvement in the total SAGIS score from 34.7 (± 15.4) at baseline to 26.0 (± 16.8) at 2 weeks and 25.6 (± 17.8) at 6 weeks post-treatment. Similarly, compared to baseline there was a statistically significant improvement in SAGIS subscores for dyspepsia and diarrhea (all p < 0.05) and effects persisted for 6 weeks post-treatment. Similarly, the symptom score (and subscores) following a standardized nutrient challenge improved significantly (p < 0.001) 2 weeks post-treatment. The presence of concomitant IBS did not significantly influence the improvement of symptoms after antibiotic therapy (all p > 0.5). CONCLUSIONS: In FD patients, the response to antimicrobial therapy with rifaximin is not influenced by concomitant IBS symptoms.