BACKGROUND: Microbial factors are likely to be involved in the recurrence of Crohn's disease (CD) after bowel resection. We investigated the luminal microbiota before and longitudinally after surgery, in relation to disease recurrence, using 16S metagenomic techniques. METHODS: In the prospective Post-Operative Crohn's Endoscopic Recurrence (POCER) study, fecal samples were obtained before surgery and 6, 12, and 18 months after surgery from 130 CD patients. Endoscopy was undertaken to detect disease recurrence, defined as Rutgeerts score ≥i2, at 6 months in two-thirds of patients and all patients at 18 months after surgery. The V2 region of the 16S rRNA gene was sequenced using Illumina MiSeq. Cluster analysis was performed at family level, assessing microbiome community differences between patients with and without recurrence. RESULTS: Six microbial cluster groups were identified. The cluster associated with maintenance of remission was enriched for the Lachnospiraceae family [adjusted OR 0.47 (0.27-0.82), P = .007]. The OTU diversity of Lachnospiraceae within this cluster was significantly greater than in all other clusters. The cluster enriched for Enterobacteriaceae was associated with an increased risk of disease recurrence [adjusted OR 6.35 (1.24-32.44), P = .026]. OTU diversity of Enterobacteriaceae within this cluster was significantly greater than in other clusters. CONCLUSIONS: Luminal bacterial communities are associated with protection from, and the occurrence of, Crohn's disease recurrence after surgery. Recurrence may relate to a higher abundance of facultatively anaerobic pathobionts from the Enterobacteriaceae family. The ecologic change of depleted Lachnospiraceae, a genus of butyrate-producing bacteria, may permit expansion of Enterobacteriaceae through luminal environmental perturbation.

Background: Factors beyond the Psoriasis Area and Severity Index (PASI) contribute to disease severity in psoriasis and potentially affect treatment responses.Objective: This subset analysis of data from two phase 3 clinical studies assessed baseline parameters in patients with different degrees of psoriasis severity in order to determine treatment responses to ixekizumab and safety outcomes.Methods: This study used integrated data from the UNCOVER-2 and -3 trials involving 2709 patients with chronic plaque psoriasis to assess the efficacy and safety of ixekizumab in three subgroups of patients, defined by PASI > 15 (group 1), PASI > 15 and history of ≥3 non-biologic systemic therapies (group 2), or PASI = 12-15 (group 3).Results: In groups 1 and 2, additional baseline features were identified that could influence treatment responses, including age at disease onset, Dermatology Life Quality Index, and work productivity. Irrespective of subgroup, ixekizumab demonstrated high PASI responses at weeks 12 and 60, which were evident as early as week 2. Adverse events did not differ across subgroups.Conclusion: Our data support the efficacy, early onset of action, and maintained response of ixekizumab as observed in previous trials, and highlight the complexity of comprehensively defining disease severity in psoriasis.

INTRODUCTION: This study sought to determine change in chronic condition risk factors in a remote Indigenous community following a 3-year period of community-led health promotion initiatives. METHODS: Data were compared between two cross-sectional surveys of Indigenous Australian community residents before and after health promotion activities, and longitudinal analysis of participants present at both surveys using multilevel mixed-effects regression. RESULTS: At baseline, 294 (53% women; mean age 35 years) participated and 218 attended the second survey (56% women, mean age 40 years), and 87 attended both. Body composition, blood pressure and urinary albumin-to-creatinine ratio remained stable between baseline and follow-up. After adjusting for age and sex, haemoglobin A1c significantly increased (from 57 to 63 mmol/mol (7.5% to 8.1%), p=0.021) for those with diabetes. Increases were also observed for total cholesterol (from 4.4 to 4.6 mmol/L, p=0.006) and triglycerides (from 1.5 to 1.6 mmol/L, p=0.019), and high-density lipoprotein cholesterol levels improved (from 0.98 to 1.02 mmol/L, p=0.018). Self-reported smoking prevalence was high but stable between baseline (57%) and follow-up (56%). Similar results were observed in the longitudinal analysis to the cross-sectional survey comparison. CONCLUSION: Community-led health promotion initiatives may have had some benefits on chronic condition risk factors, including stabilisation of body composition, in this remote Indigenous community. Given that less favourable trends were observed for diabetes and total cholesterol over a short time period and smoking prevalence remained high, policy initiatives that address social and economic disadvantage are needed alongside community-led health promotion initiatives.

BACKGROUND: The advent of direct-acting antivirals (DAAs) and point-of-care (POC) testing platforms for hepatitis C allow for the decentralization of care to primary care settings. In many countries, access to DAAs is generally limited to tertiary hospitals, with limited published research documenting decentralized models of care in low-and middle-income settings. OBJECTIVE: This study aims to assess the feasibility, acceptability, effectiveness, and cost-effectiveness of decentralized community-based POC testing and DAA therapy for hepatitis C among people who inject drugs and the general population in Yangon, Myanmar. METHODS: Rapid diagnostic tests for anti-hepatitis C antibodies were carried out on-site and, if reactive, were followed by POC GeneXpert hepatitis C RNA polymerase chain reaction tests. External laboratory blood tests to exclude other major health issues were undertaken. Results were given to participants at their next appointment, with the participants commencing DAA therapy that day if a specialist review was not required. Standard clinical data were collected, and the participants completed behavioral questionnaires. The primary outcome measures are the proportion of participants receiving GeneXpert hepatitis C RNA test, the proportion of participants commencing DAA therapy, the proportion of participants completing DAA therapy, and the proportion of participants achieving sustained virological response 12 weeks after completing DAA therapy. RESULTS: Recruitment was completed on September 30, 2019. Monitoring visits and treatment outcome visits are scheduled to continue until June 2020. CONCLUSIONS: This feasibility study in Myanmar contributes to the evidence gap for community-based hepatitis C care in low- and middle-income settings. Evidence from this study will inform the scale-up of hepatitis C treatment programs in Myanmar and globally.

BACKGROUND: The importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Rates of cardiovascular disease are much higher in people with both diabetes and kidney dysfunction than in those with only one of these conditions. By the time these people are identified in current clinical practice, proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease, in turn providing targeted intervention to improve patient outcomes. OBJECTIVE: This study aims to identify potential biomarkers in people with diabetes and chronic kidney disease (CKD) associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers will be explored, including DNA methylation profiles in blood lymphocytes, the metabolomic profile of blood-derived plasma and urine, and the gut microbiome. METHODS: The cross-sectional study recruited 121 people with diabetes and varying stages (stages 1-5) of chronic kidney disease. Single-point data collection included blood, urine, and fecal samples in addition to clinical data such as anthropometric measurements and biochemical parameters. Additional information obtained from medical records included patient demographics, medical comorbidities, and medications. RESULTS: Data collection commenced in January 2018 and was completed in June 2018. At the time of submission, 121 patients had been recruited, and 119 samples remained after quality control. There were 83 participants in the early diabetes-associated CKD group with a mean estimated glomerular filtration rate (eGFR) of 61.2 mL/min/1.73 m2 (early CKD group consisting of stage 1, 2, and 3a CKD), and 36 participants in the late diabetic CKD group with a mean eGFR of 23.9 mL/min/1.73 m2 (late CKD group, consisting of stage 3b, 4, and 5), P<.001. We have successfully obtained DNA for methylation and microbiome analyses using the biospecimens collected via this protocol and are currently analyzing these results together with the metabolome of this cohort of individuals with diabetic CKD. CONCLUSIONS: Recent advances have improved our understanding of the epigenome, metabolomics, and the influence of the gut microbiome on the incidence of diseases such as cancers, particularly those related to environmental exposures. However, there is a paucity of literature surrounding these influencers in renal disease. This study will provide insight into the fundamental understanding of the pathophysiology of CKD in individuals with diabetes, especially in novel areas such as epigenetics, metabolomics, and the kidney-gut axis. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16277.

To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.0 ± 1.6 years). Relative to controls, in men, at the distal radius, cases had smaller cortical cross sectional area (CSA) (p = 0.012), higher porosity of the outer transitional zone (OTZ) (p = 0.006), inner transitional zone (ITZ) (p = 0.043) and the compact-appearing cortex (CC) (p = 0.023) while trabecular vBMD was lower (p = 0.002). At the distal tibia, cases also had a smaller cortical CSA (p = 0.008). Cortical porosity was not higher, but trabecular vBMD was lower (p = 0.001). Relative to controls, in women, cases had higher distal radial porosity of the OTZ (p = 0.028), ITZ (p = 0.030) not CC (p = 0.054). Trabecular vBMD was lower (p = 0.041). Distal tibial porosity was higher in the OTZ (p = 0.035), ITZ (p = 0.009), not CC. Stress fractures are associated with compromised cortical and trabecular microstructure.

Case-control studies of breast cancer have consistently shown that pathogenic variants in CHEK2 are associated with about a 3-fold increased risk of breast cancer. Information about the recurrent protein-truncating variant CHEK2 c.1100delC dominates this estimate. There have been no formal estimates of age-specific cumulative risk of breast cancer for all CHEK2 pathogenic (including likely pathogenic) variants combined. We conducted a population-based case-control-family study of pathogenic CHEK2 variants (26 families, 1071 relatives) and estimated the age-specific cumulative risk of breast cancer using segregation analysis. The estimated hazard ratio for carriers of pathogenic CHEK2 variants (combined) was 4.9 (95% CI 2.5-9.5) relative to non-carriers. The HR for carriers of the CHEK2 c.1100delC variant was estimated to be 3.5 (95% CI 1.02-11.6) and the HR for carriers of all other CHEK2 variants combined was estimated to be 5.7 (95% CI 2.5-12.9). The age-specific cumulative risk of breast cancer was estimated to be 18% (95% CI 11-30%) and 33% (95% CI 21-48%) to age 60 and 80 years, respectively. These findings provide important information for the clinical management of breast cancer risk for women carrying pathogenic variants in CHEK2.

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. We aimed to investigate the effect of maternal and postnatal high LA (HLA) diet on plasma FA composition, plasma and hepatic lipids and genes involved in lipid metabolism in the liver of adult offspring. Female rats were fed with low LA (LLA; 1.44% LA) or HLA (6.21% LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), fed either LLA or HLA diets and sacrificed at PN180. Postnatal HLA diet decreased circulating total n-3 PUFA and alpha-linolenic acid (ALA), while increased total n-6 PUFA, LA and arachidonic acid (AA) in both male and female offspring. Maternal HLA diet increased circulating leptin in female offspring, but not in males. Maternal HLA diet decreased circulating adiponectin in males. Postnatal HLA diet significantly decreased aspartate transaminase (AST) in females and downregulated total cholesterol, HDL-cholesterol and triglycerides in the plasma of males. Maternal HLA diet downregulated the hepatic mRNA expression of Hmgcr in both male and female offspring and decreased the hepatic mRNA expression of Cpt1a and Acox1 in females. Both maternal and postnatal HLA diet decreased hepatic mRNA expression of Cyp27a1 in females. Postnatal diet significantly altered circulating fatty acid concentrations, with sex-specific differences in genes that control lipid metabolism in the adult offspring following exposure to high LA diet in utero.

BACKGROUND: Shared decision making (SDM) is becoming an important part of ulcerative colitis (UC) management because of the increasing complexity of available treatment choices and their trade-offs. The use of decision aids (DA) may be effective in increasing patients' participation in UC management but their uptake has been limited due to high attrition rates and lack of a participatory approach to their design and implementation. OBJECTIVE: The primary aim of this study is to explore the perspectives of Australian patients and their clinicians regarding the feasibility and acceptability of myAID, a web-based DA, in informing treatment decisions in UC. The secondary aim is to use the findings of this pilot study to inform the design of a cluster randomized clinical trial (CRCT) to assess the efficacy of the DA compared with usual care. METHODS: myAID, a DA was designed and developed using a participatory approach by a multidisciplinary team of clinicians, patients, and nonmedical volunteers. A qualitative pilot study to evaluate the DA, involving patients with UC facing new treatment decisions and inflammatory bowel disease clinicians, was undertaken. RESULTS: A total of 11 patients with UC and 15 clinicians provided feedback on myAID. Themes explored included the following: Acceptability and usability of myAID-myAID was found to be acceptable by the majority of clinicians as a tool to facilitate SDM, uptake was thought to vary depending on clinicians' approaches to patient education and practice, potential to overcome time restrictions associated with outpatient clinics was identified, presentation of unbiased information enabling patients to digest information at their own pace was noted, and potential to provoke anxiety among patients with a new diagnosis or mild disease was raised; Perceived role and usefulness of myAID-discordance was observed between patients who prioritized voicing preferences and clinicians who prioritized treatment adherence, and myAID facilitated early discussion of medical versus surgical treatment options; Target population and timing of use-greatest benefit was perceived at the time of initiating or changing treatment and following commencement of immunosuppressive therapy; and Potential concerns and areas for improvement-some perceived that use of myAID may precipitate anxiety by increasing decisional conflict and impact the therapeutic relationship between patient and the clinician and may increase resource requirements. CONCLUSIONS: These preliminary findings suggest that patients and clinicians consider myAID as a feasible and acceptable tool to facilitate SDM for UC management. These pilot data have informed a participatory approach to the design of a CRCT, which will evaluate the clinical efficacy of myAID compared with usual care. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12617001246370; http://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617001246370.

BACKGROUND: Emerging evidence suggests that people with arthritis are reporting increased physical pain and psychological distress during the COVID-19 pandemic. At the same time, Twitter's daily usage has surged by 23% throughout the pandemic period, presenting a unique opportunity to assess the content and sentiment of tweets. Individuals with arthritis use Twitter to communicate with peers, and to receive up-to-date information from health professionals and services about novel therapies and management techniques. OBJECTIVE: The aim of this research was to identify proxy topics of importance for individuals with arthritis during the COVID-19 pandemic, and to explore the emotional context of tweets by people with arthritis during the early phase of the pandemic. METHODS: From March 20 to April 20, 2020, publicly available tweets posted in English and with hashtag combinations related to arthritis and COVID-19 were extracted retrospectively from Twitter. Content analysis was used to identify common themes within tweets, and sentiment analysis was used to examine positive and negative emotions in themes to understand the COVID-19 experiences of people with arthritis. RESULTS: In total, 149 tweets were analyzed. The majority of tweeters were female and were from the United States. Tweeters reported a range of arthritis conditions, including rheumatoid arthritis, systemic lupus erythematosus, and psoriatic arthritis. Seven themes were identified: health care experiences, personal stories, links to relevant blogs, discussion of arthritis-related symptoms, advice sharing, messages of positivity, and stay-at-home messaging. Sentiment analysis demonstrated marked anxiety around medication shortages, increased physical symptom burden, and strong desire for trustworthy information and emotional connection. CONCLUSIONS: Tweets by people with arthritis highlight the multitude of concurrent concerns during the COVID-19 pandemic. Understanding these concerns, which include heightened physical and psychological symptoms in the context of treatment misinformation, may assist clinicians to provide person-centered care during this time of great health uncertainty.