Masking for COVID-19 and other respiratory viral infections: implications of the available evidence.

The use of face masks has been widely promoted and at times mandated to prevent coronavirus disease 2019 (COVID-19). The 2023 publication of an updated Cochrane review on mask effectiveness for respiratory viruses as well as the unfolding epidemiology of COVID-19 underscore the need for an unbiased assessment of the current scientific evidence. It appears that the widespread promotion, adoption, and mandating of masking for COVID-19 were based not primarily on the strength of evidence for effectiveness but more on the imperative of decision-makers to act in the face of a novel public health emergency, with seemingly few good alternatives. Randomized clinical trials of masking for prevention of COVID-19 and other respiratory viruses have so far shown no evidence of benefit (with the possible exception of continuous use of N95 respirators by hospital workers). Observational studies provide lower-quality evidence and do not convincingly demonstrate benefit from masking or mask mandates. Unless robust new evidence emerges showing the effectiveness of masks in reducing infection or transmission risks in either trials or real-world conditions, mandates are not warranted for future epidemics of respiratory viral infections.

Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986-2020.

BACKGROUND: Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya. METHODS: HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters. RESULTS: Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016-20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011-15), but dropped to 6.5% (2016-20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000-08], indicating propagation over 12 years. CONCLUSIONS: Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya.

Impact of coronavirus disease 2019-related clinic closures on HIV incidence in young adult MSM and transgender women in Kenya.

INTRODUCTION: Little is known about the impact that the COVID-19 pandemic had on risk of HIV acquisition in sub-Saharan Africa. We assessed the impact of COVID-19-related clinic closures on HIV incidence in a cohort of gay, bisexual, and other men who have sex with men (MSM) and transgender women in Kenya. METHODS: MSM and transgender women enrolled in a prospective, multicentre cohort study were followed quarterly for HIV testing, behaviour assessments, and risk. We estimated the HIV incidence rate and its 95% credible intervals (CrI) among participants who were HIV-negative before COVID-19-related clinic closure, comparing incidence rate and risk factors associated with HIV acquisition before vs. after clinic reopening, using a Bayesian Poisson model with weakly informative priors. RESULTS: A total of 690 (87%) participants returned for follow-up after clinic reopening (total person-years 664.3 during clinic closure and 1013.3 after clinic reopening). HIV incidence rate declined from 2.05/100 person-years (95% CrI = 1.22-3.26, n  = 14) during clinic closures to 0.96/100 person-years (95% CrI = 0.41-2.07, n  = 10) after clinic reopening (IRR = 0.47, 95% CrI = 0.20-1.01). The proportion of participants reporting hazardous alcohol use and several sexual risk behaviours was higher during clinic closures than after clinic reopening. In multivariable analysis adjusting for study site and participant characteristics, HIV incidence was lower after clinic reopening (IRR 0.57, 95% CrI = 0.23-1.33). Independent risk factors for HIV acquisition included receptive anal intercourse (IRR 1.94, 95% CrI = 0.88-4.80) and perceived risk of HIV (IRR 3.03, 95% CRI = 1.40-6.24). CONCLUSION: HIV incidence during COVID-19-related clinic closures was moderately increased and reduced after COVID-19 restrictions were eased. Ensuring access to services for key populations is important during public health emergencies.

The Pain Anxiety Symptom Scale: Initial Development and Evaluation of 4 and 8 Item Short Forms.

Elevated levels of anxiety in relation to chronic pain have been consistently associated with greater distress and disability. Thus, accurate measurement of pain-related anxiety is an important requirement in modern pain services. The Pain Anxiety Symptom Scale (PASS) was introduced over 30 years ago, with a shortened 20-item version introduced 10 years later. Both versions of the PASS were derived using Principal Components Analysis, an established method of measure development with roots in classical test theory. Item Response Theory (IRT) is a complementary approach to measure development that can reduce the number of items needed and maximize item utility with minimal loss of statistical and clinical information. The present study used IRT to shorten the 20-item PASS (PASS-20) in a large sample of people with chronic pain (N = 2,669). Two shortened versions were evaluated, 1 composed of the single best-performing item from each of its 4 subscales (PASS-4) and the other with the 2 best-performing items from each subscale (PASS-8). Several supplementary analyses were performed, including comparative item convergence evaluations based on sample characteristics (ie, female or male sex; clinical or online sample), factor invariance testing, and criterion validity evaluation of the 4, 8, and 20-item versions of the PASS in hierarchical regression models predicting pain-related distress and interference. Overall, both shortened PASS versions performed adequately across these supplemental tests, although the PASS-4 had more consistent item convergence between samples, stronger evidence for factor invariance, and accounted for 83% of the variance accounted for by the PASS-20% and 92% of the variance accounted for by the PASS-8 in criterion variables. Consequently, the PASS-4 is recommended for use in situations where a briefer evaluation of pain-related anxiety is appropriate. PERSPECTIVE: The Pain Anxiety Symptom Scale (PASS) is an established measure of pain-related fear. This study derived 4 and 8-item versions of the PASS using IRT. Both versions showed strong psychometric properties, stability of factor structure, and relation to important aspects of pain-related functioning.

Can datasets from long-term biomonitoring programs detect climate change effects on stream benthos?

We analyzed datasets from a long-term monitoring program of stream ecosystems in British Columbia, Canada, to determine whether or not it could detect climate change effects. In the Fraser River Basin (monitoring timespan 1994-2019), there was a marked (∼50%) increase in alpha diversity in reference streams, while BC North Coast (2004-2021) streams showed a modest trend of decreasing diversity and Columbia River Basin (2003-2018) and Vancouver Island (2001-2019) streams showed modestly increasing diversity. In all four regions, diversity across all sites in a specific period was primarily a function of sampling effort during this period rather than a temporal trend. Across all the regions, only three of 21 groups of faunally similar sites defined by Reference Condition Approach predictive modeling showed a suggestion of a directional change in community structure over time. Only 1 of 15 reference sites that were repeatedly sampled over several years showed a pattern that may indicate a response to changing climate. Three, not mutually exclusive, reasons why we did not see a clear effect of climate change on BC stream ecosystems were: 1) Little or no effect of climate change relative to other, potentially interacting biotic and abiotic factors, 2) The timespan of monitoring was too short to detect cumulative effects of climate change, and, most importantly, 3) The sampling design and protocol were unable to detect climate change effects. To better detect and characterize the effects of climate change on streams in monitoring programs, we recommend annual re-sampling of a few reference sites and detailed analysis of the natural and human environment of the sites along with better characterization of the benthic community (e.g. with eDNA) at all monitored sites.

A chair-stand time of greater than 15 seconds is associated with an increased risk of death and hospitalization in cirrhosis.

Background: Frailty is a clinical state of increased vulnerability and is common in patients with cirrhosis. The liver frailty index (LFI) is a validated tool to evaluate frailty in cirrhosis, comprising of grip strength, chair stands, and balance tests. The chair-stand test is an easy to conduct frailty subcomponent that does not require specialized equipment and may be valuable to predict adverse clinical outcomes in cirrhosis. The objective of this study was to determine if the chair-stand test is an independent predictor of mortality and hospitalization in cirrhosis. Methods: A retrospective review of 787 patients with cirrhosis was conducted. Chair-stand times were collected at baseline in person and divided into three groups: <10 seconds (n = 276), 10-15 seconds (n = 290), and >15 seconds (n = 221). Fine-Gray proportional hazards regression models were used to evaluate the association between chair-stand times and the outcomes of mortality and non-elective hospitalization. Results: The hazard of mortality (HR 3.21, 95% CI 2.16%-4.78%, p <0.001) and non-elective hospitalization (HR 2.24, 95% CI 1.73%-2.91%, p <0.001) was increased in group 3 in comparison to group 1. A chair-stand test time >15 seconds had increased all-cause mortality (HR 2.78, 95% CI 2.01%-3.83%, p <0.001) and non-elective hospitalizations (HR 1.84, 95% CI 1.48%-2.29%, p <0.001) compared to <15 seconds. Conclusions: A chair-stand test time of >15 seconds is independently associated with mortality and non-elective hospitalizations. This test holds promise as a rapid prognostication tool in cirrhosis. Future work will include external validation and virtual assessment in this population.

Diagnosis of esophageal varices by liver stiffness and serum biomarkers in virus-related compensated advanced chronic liver disease.

Background: Individuals infected with hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency (HIV) viruses can experience compensated advanced chronic liver disease (cACLD) leading to esophageal varices (EV). In patients at low risk of esophageal varices needing treatment (EVNT), non-invasive criteria based on liver stiffness measurement (LSM) with platelets, or fibrosis biomarkers, may avoid unnecessary screening esophagogastroduodenoscopies (EGD). These approaches have not been compared among people infected with HIV, HBV, and HCV patients. Methods: Patients with a diagnosis of cACLD (LSM ≥10 kPa) and EGD availability were included from two cohorts. Baveno VI and expanded Baveno VI criteria (based on LSM and platelets), fibrosis biomarkers Fibrosis-4 Index (FIB-4), AST-to-Platelets Ratio Index (APRI), AST-to-ALT ratio (AAR), and RESIST criteria (based on platelets and albumin) were applied to determine the proportion of spared EGD and of missed EVNT. Results: Three hundred fifty three patients (30.6% with HIV, 25.3% monoinfected with HBV, and 44.1% with HCV) were included. The prevalence of EVNT was 8.2%. Both Baveno VI and expanded Baveno VI criteria performed well in patients with virus-related cACLD, by sparing 26.1% and 51.6% EGD, respectively, while missing <2% EVNT. The proportion of spared EGD were 48.2%, 58%, and 24.3% by FIB-4 (<2.78), APRI (<1.1), and AAR (<0.75), respectively, while missing <3% EVNT. RESIST criteria spared 47.8% EGD while missing 1.9% EVNT. Conclusions: Non-invasive criteria based on LSM can spare unnecessary EGD in virus-related cACLD. Simple fibrosis biomarkers can ameliorate resource utilization for EVNT screening in low resource settings.

Antimicrobial and Adjuvant Potencies of Di-n-alkyl Substituted Diazalariat Ethers.

Lariat ethers are macrocyclic polyethers-crown ethers-to which sidearms are appended. 4,13-Diaza-18-crown-6 having twin alkyl chains at the nitrogens show biological activity. They exhibit antibiotic activity, but when co-administered at with an FDA-approved antibiotic, the latter's potency is often strongly enhanced. Potency enhancements and resistance reversals have been documented in vitro for a range of Gram-negative and Gram-positive bacteria with a variety of antimicrobials. Strains of E. coli and Staphylococcus aureus having resistance to a range of drugs have been studied and the potency enhancements (checkerboards) are reported here. Drugs included in the present study are ampicillin, cefepime, chlortetracycline, ciprofloxacin, doxycycline, kanamycin, minocycline, norfloxacin, oxycycline, penicillin G, and tetracycline. Enhancements of norfloxacin potency against S. aureus 1199B of up to 128-fold were observed. The properties of these lariat ethers have been studied to determine solubility, their membrane penetration, cytotoxicity and mammalian cell survival, and their effect on bacterial efflux pumps. It is shown that in some cases, the lariat ethers have complex antimicrobials with considerable selectivity. Based on these observations, including 1:1 complexation between lariat ethers and antimicrobials and the cytotoxicity of the MeI salts showing a separation index of 32-fold, they hold significant potential for further development.

Design of a syringe extension device (Chloe SED®) for low-resource settings in sub-Saharan Africa: a circular economy approach.

Underfunded healthcare infrastructures in low-resource settings in sub-Saharan Africa have resulted in a lack of medical devices crucial to provide healthcare for all. A representative example of this scenario is medical devices to administer paracervical blocks during gynaecological procedures. Devices needed for this procedure are usually unavailable or expensive. Without these devices, providing paracervical blocks for women in need is impossible resulting in compromising the quality of care for women requiring gynaecological procedures such as loop electrosurgical excision, treatment of miscarriage, or incomplete abortion. In that perspective, interventions that can be integrated into the healthcare system in low-resource settings to provide women needing paracervical blocks remain urgent. Based on a context-specific approach while leveraging circular economy design principles, this research catalogues the development of a new medical device called Chloe SED® that can be used to support the provision of paracervical blocks. Chloe SED®, priced at US$ 1.5 per device when produced in polypropylene, US$ 10 in polyetheretherketone, and US$ 15 in aluminium, is attached to any 10-cc syringe in low-resource settings to provide paracervical blocks. The device is designed for durability, repairability, maintainability, upgradeability, and recyclability to address environmental sustainability issues in the healthcare domain. Achieving the design of Chloe SED® from a context-specific and circular economy approach revealed correlations between the material choice to manufacture the device, the device's initial cost, product durability and reuse cycle, reprocessing method and cost, and environmental impact. These correlations can be seen as interconnected conflicting or divergent trade-offs that need to be continually assessed to deliver a medical device that provides healthcare for all with limited environmental impact. The study findings are intended to be seen as efforts to make available medical devices to support women's access to reproductive health services.

Transgender women in Kenya experience greater stigma, depressive symptoms, alcohol and drug use and risky sexual practices than cis-gendered men who have sex with men.

BACKGROUND: Worldwide, sexual and gender minority individuals have disproportionate burden of HIV. There are limited quantitative data from sub-Saharan Africa on the intersection of risks experienced by transgender women (TGW) in comparison to cis-men who have sex with men (MSM). This analysis addresses this gap by comparing reported stigma, psychosocial measures of health, and sexual risk practices between TGW and cis-MSM in Kenya. METHODS: We analyzed data from the baseline visit of an ongoing prospective cohort study taking place in three diverse metropolitan areas. Eligible participants were HIV-negative, assigned male at birth, ages 18-29 years, and reported anal intercourse in the past 3 months with a man or TGW. Data collected by audio computer assisted self-interview included sociodemographic measures, and sexual practices occurring in the past 3 months. Multivariable regressions assessed differences between TGW and cis-MSM in selected sexual practices, depressive symptoms, alcohol and drug use, and stigma. RESULTS: From September, 2019, through May, 2021, 838 participants were enrolled: 108 (12.9%) TGW and 730 (87.1%) cis-MSM. Adjusting for sociodemographic variables, TGW were more likely than cis-MSM to report: receptive anal intercourse (RAI; adjusted prevalence ratio [aPR] = 1.59, 95% CI: 1.32 - 1.92), engaging in group sex (aPR = 1.15, 95% CI: 1.04 - 1.27), 4 or more male sex partners (aPR = 3.31, 95% CI: 2.52 - 4.35), and 3 or more paying male sex partners (aPR = 1.58, 95% CI: 1.04 - 2.39). TGW were also more likely to report moderate to severe depressive symptoms (aPR = 1.42, 95% CI: 1.01 - 1.55), and had similar alcohol and drug abuse scores as cis-MSM. In sensitivity analysis, similar to TGW, male-identifying individuals taking feminizing gender affirming therapy had an increased likelihood of reporting RAI and group sex, and greater numbers of male sex partners and paying male sex partners relative to cis-MSM. CONCLUSIONS: Across three metropolitan areas in Kenya, TGW were more likely to report depressive symptoms and increased sexual risk taking. We identified a need for research that better characterizes the range of gender identities. Our analysis affirms the need for programmatic gender-affirming interventions specific to transgender populations in Kenya and elsewhere in Africa.

Challenges with PrEP Uptake and Adherence Among Gay, Bisexual, and Other Men Who Have Sex with Men in Kisumu, Kenya.

Data on challenges with pre-exposure prophylaxis (PrEP) uptake and adherence among Kenyan gay, bisexual, and other men who have sex with men (GBMSM) are limited. In this mixed-methods sequential explanatory design study, our quantitative phase followed 157 at-risk, HIV-negative GBMSM who accepted PrEP and enrolled in a cohort with 12-month follow-up. Stored dried blood spots collected at two intervals were batch tested for tenofovir diphosphate (TFV-DP) concentrations at study end. Despite high self-reported adherence, only 14.6% of individuals had protective TFV-DP levels at any visit. Protective TFV-DP levels were positively associated with injection drug use and a self-assessed moderate risk of acquiring HIV, and negatively associated with time since enrolment. In our subsequent qualitative phase, an intensive workshop was conducted with the GBMSM community to identify barriers and facilitators to PrEP uptake and adherence. These data revealed numerous challenges with traditional PrEP programs that must be addressed through community collaborations.

RESUMEN: La evidencia respecto a desafíos existentes con aceptación y adherencia de la profilaxis previa a la exposición (PrEP) de VIH, entre los hombres homosexuales, bisexuales y otros hombres que tienen sexo con hombres (GBMSM) en Kenia es limitada. Condujimos un estudio de métodos mixtos y diseño explicativo secuencial. En la fase cuantitativa seguimos a 157 GBMSM VIH-negativos en riesgo que aceptaron PrEP y se inscribieron en una cohorte con un seguimiento de 12 meses. Analizamos, por lotes y al final del estudio, gotas de sangre seca recolectada a dos intervalos de tiempo y previamente almacenada, para determinar las concentraciones de difosfato de tenofovir (TFV-DP). A pesar de la alta adherencia autoinformada, solo el 14,6% de las personas tenían niveles protectores de TFV-DP en alguna visita. Los niveles protectores de TFV-DP se asociaron positivamente con el uso de drogas inyectables y un riesgo moderado autoevaluado de contraer el VIH, y negativamente con el tiempo transcurrido desde la inscripción. En la fase cualitativa posterior, conversamos con GBMSM de la comunidad para identificar las barreras y los facilitadores para la concientización, aceptación, adherencia y retención a PrEP. Estos datos revelaron numerosos desafíos con los programas tradicionales de PrEP que deben abordarse mediante colaboraciones comunitarias.

URCHOICE: Preferences for Pre-Exposure Prophylaxis (PrEP) Options for HIV Prevention Among Kenyan men who have sex with men and Transgender Women in Nairobi, Kisumu and the Coast.

HIV prevention method preferences were evaluated among Kenyan men who have sex with men (MSM) and transgender women (TW) from three sites: Kisumu, Nairobi and the Coast. Information sessions detailing the attributes, duration of protection, route of administration and probable visibility were attended by 464 HIV negative participants, of whom 423 (median age: 24 years) agreed to be interviewed. Across pairwise comparisons daily PrEP was by far the least preferred (1%); quarterly injections (26%) and monthly pills (23%) were most preferred, followed by yearly implant (19%) and condoms (12%). When participants were "forced" to choose their most preferred PrEP option, only 10 (2.4%) chose the daily pill; more (37.1%) chose the quarterly injection than the monthly pill (34.8%) and the yearly implant (25.8%). TW preferred the yearly implant over the quarterly injection. To achieve the rates of PrEP uptake and adherence necessary for protecting large proportions of vulnerable MSM and TW, a variety of long-acting products should be developed and made accessible to appeal to a diversity of preferences.

Geographic and socioeconomic access disparities to Phase 3 clinical trials in ophthalmology in the United States.

BACKGROUND/OBJECTIVE: To identify geographic and socioeconomic variables associated with residential proximity to Phase 3 ophthalmology clinical trial sites. METHODS: The geographic location of clinical trial sites for Phase 3 clinical trials in ophthalmology was identified using ClinicalTrials.gov. Driving time from each United States (US) census tract centroid to nearest clinical trial site was calculated using real traffic patterns. Travel data were crosslinked to census-tract level public datasets from United States Census Bureau American Community Survey (ACS). Cross-sectional multivariable regression was used to identify associations between census-tract sociodemographic factors and driving time (>60 min) from each census tract centroid to the nearest clinical trial site. RESULTS: There were 2330 unique clinical trial sites and 71,897 census tracts. Shortest median time was to retina sites [33.7 min (18.7, 70.1 min)]. Longest median time was to neuro-ophthalmology sites [119.8 min (48.7, 240.4 min)]. Driving >60 min was associated with rural tracts [adjusted odds ratio (aOR) 7.60; 95% CI (5.66-10.20), p < 0.0001]; Midwest [aOR 1.84(1.15-2.96), p = 0.01], South [aOR 2.57 (1.38-4.79), p < 0.01], and West [aOR 2.52 (1.52-4.17), p < 0.001] v. Northeast; and tracts with higher visual impairment [aOR 1.07 (1.03-1.10), p < 0.001)]; higher poverty levels [4th v.1st Quartile of population below poverty, aOR 2.26 (1.72-2.98), p < 0.0001]; and lower education levels [high school v. Bachelor's degree or higher aOR 1.02 (1.00-1.03), p = 0.0072]. CONCLUSIONS: There are significant geographic and socioeconomic disparities in access to ophthalmology clinical trial sites for rural, non-Northeastern, poorer, and lower education level census tracts, and for census tracts with higher levels of self-reported visual impairment.

Clinical Outcomes and Quantitative HBV Surface Antigen Levels in Diverse Chronic Hepatitis B Patients in Canada: A Retrospective Real-World Study of CHB in Canada (REVEAL-CANADA).

BACKGROUND: Hepatitis B surface antigen (HBsAg) loss is associated with improved clinical outcomes for individuals with chronic hepatitis B (CHB); however, the effects of varying HBsAg levels on clinical outcomes in diverse cohorts are understudied. METHODS: In this cross-sectional, multicentre, retrospective study, the data on adult subjects enrolled in the Canadian HBV Network with CHB seen from 1 January 2012 to 30 January 2021 with the treatment and virologic data within 1 year of HBsAg testing were analyzed. Patients were tested for HBsAg using qualitative (for HBsAg-negative samples) and/or commercial quantitative assays. Fibrosis or hepatic necroinflammation was determined by the liver stiffness measurement (LSM). The baseline data were summarized using descriptive statistics and compared by using univariable/multivariable analyses. RESULTS: This study included 844 CHB patients, with a median age of 49.6 years (IQR 40.1-60.5), and 37% were female. In total, 751 patients (78.6%) had known ethnicity data, and 76.7% self-reported as Asian, 11.4% as Black, 6.8% as White, and 4.8% as other. Among the 844 patients, 237 (28.0%) were HBsAg (-) (1000 IU/mL. Overall, 80% (682) had known HBeAg status at the last follow-up, and the majority (87.0%) were HBeAg-negative. In addition, 54% (461/844) had prior antiviral therapy, 19.7% of which (16.3, 23.7, n = 91) were HBsAg (-). The treated patients had a lower risk of cirrhosis (16.46, 95% CI 1.89-143.39, p = 0.01) or HCC (8.23, 95% CI 1.01-67.39, p = 0.05) than the untreated patients. A lower proportion of the HBsAg-loss group had cirrhosis (5.7% vs. 10.9%, p = 0.021) and HCC (0.9% vs. 6.2%, p = 0.001). CONCLUSION: In this retrospective, ethnically diverse cohort study, CHB patients who received antiviral therapy and/or had HBsAg loss were less likely to develop cirrhosis and HCC, confirming the results of the studies in less diverse cohorts. No association was found between the qHBsAg level and fibrosis determined with LSM. Individuals who achieved HBsAg loss had low-level qHBsAg within 1 year of seroclearance.

A randomized controlled trial of a multicomponent online stress reduction intervention in inflammatory bowel disease.

Background: Psychological stress negatively impacts inflammatory bowel disease (IBD) outcomes. Patients have prioritized access to online interventions; yet, the data on these have been limited by mixed in-person/online interventions, low adherence, and non-randomized controlled trial (RCT) design. Objectives: We assessed the efficacy of and adherence to a 12-week online multicomponent stress reduction intervention in IBD. Design: This is a RCT. Methods: Adult participants on stable IBD medical therapy with elevated stress levels from four centers were randomized to intervention or control groups. Intervention participants received a 12-week online program including a weekly yoga, breathwork and meditation video (target 2-3 times/week), a weekly cognitive behavioral therapy/positive psychology informed video activity, and weekly 10-min check-ins by a study team member. Control participants received weekly motivational messages by email. All patients received standard of care IBD therapy. The primary outcome was Cohen's Perceived Stress Scale (PSS). Secondary outcomes evaluated mental health, resilience, health-related quality of life (HRQoL), symptom indices, acceptability, adherence, and inflammatory biomarkers. Analysis of covariance was used to determine between-group differences. Results: Of 150 screened patients, 101 were randomized to the intervention (n = 49) and control (n = 52) groups (mean age: 42.5 ± 14.1 years; M:F 1:3, 48% with ulcerative colitis and 52% with Crohn's disease). The between-group PSS improved by 22.4% (95% confidence interval, 10.5-34.3, p < 0.001). Significant improvements were seen in mental health, resilience, and HRQoL measures, with a median satisfaction score of 89/100 at the end of the 12 weeks. In the 44/49 patients who completed the intervention, 91% achieved program adherence targets. Conclusion: This 12-week online intervention improved perceived stress, mental health, and HRQoL, but did not impact IBD symptom indices or inflammatory biomarkers. The program was readily adopted and adhered to by participants with high retention rates. After iterative refinement based on participant feedback, future studies will evaluate the impact of a longer/more intense intervention on disease course. Registration: ClinicalTrials.gov Identifier NCT03831750. Plain Language Summary: An online stress reduction intervention in inflammatory bowel disease patients improves stress, mental health, and quality of life People with inflammatory bowel disease (IBD) have high levels of stress, anxiety, and depression. Although IBD patients have expressed the need for online mental wellness interventions, the existing data to support these interventions in IBD are limited. In this trial, 101 IBD patients had the chance to participate in a 12-week online stress reduction intervention. In those patients randomly selected to participate in the online intervention, each week they received the following: a 20- to 30-min yoga, breathwork, and meditation video that they were asked to do 2-3 times a week, a 10- to 20-min mental wellness activity they were asked to do once during the week, and a 10-min telephone check-in with a study team member. Participants who were not selected to use the online intervention received a weekly motivational message by email. In all, 90 of the 101 participants (89%) completed the study with the mean age of participants being 43 years and the majority being females (75%). Ninety-one percent of participants who completed the intervention met the program target of doing the yoga, breathwork, and meditation video at least 2 times per week. Significant improvements were seen in perceived stress (by 22.4%), depression (by 29.5%), anxiety (by 23.7%), resilience (by 10.6%), and quality of life (by 8.9%). No changes were seen in IBD severity or in blood markers of inflammation. In conclusion, this study demonstrates evidence that a 12-week online stress reduction intervention had low dropout rates, high adherence and beneficial effects on stress, mental health, and quality of life measures. Continued feedback will be sought from study participants and our IBD patient partners to refine the intervention and assess the impact in future studies of patients with active IBD, as well as the impact of a longer/more intense intervention.

Clinical characterization of patients with primary biliary cholangitis: A report from multiple Canadian centres.

Background: Primary biliary cholangitis (PBC) is a rare, chronic autoimmune, cholestatic liver disease affecting approximately 318 per million Canadians. There is limited information regarding the characterization of this patient population in Canada. Consequently, we aim to describe a cohort of PBC patients managed across liver centres serving this type of population. Methods: A cross-sectional examination of 1,125 PBC patient charts at 15 liver centres across Canada was conducted between January 2016 and September 2017. Results: Data from 1,125 eligible patients were collected from 7 Canadian provinces. The patient population was largely female (90.2%), had a median overall age of 61.3 years, and a median overall time since diagnosis of 6.4 years. Of the patients included in the study, 89% were on ursodeoxycholic acid (UDCA) therapy at a median dose of 14.0 mg/kg/day and 4.4% were previously treated with UDCA, whereas 6.6% were never treated with UDCA. Of the patients with available data (n = 1067), 289 (27.1%) presented with alkaline phosphatase (ALP) levels ≥200 IU/L and/or total bilirubin levels ≥21 µmol/L. Assessment of UDCA treatment response revealed that 26.6% and 38.3% of patients were inadequate responders according to the Toronto and Paris-II criteria, respectively. Mortality occurred in 1.2% (14) of patients, with liver-related adverse outcomes being more commonly observed in patients who discontinued UDCA compared to those who are currently on treatment (36.3% and 19.6%, respectively). Conclusion: This study showed that Canadian PBC patients present with demographics and features commonly reported in the literature for this disease. Over one third of PBC patients had inadequate response to UDCA treatment or were not currently being treated with UDCA. Consequently, there is a significant unmet therapeutic need in this Canadian PBC population.

The Assessment of Driving Fitness Using an On-Road Evaluation in Patients With Cirrhosis.

INTRODUCTION: The association between cirrhosis and driving performance is of particular clinical relevance because of the life-threatening safety issues both for the driver with cirrhosis and the general public. Study aims were to assess (i) driving competency through the use of an in-office computerized battery and on-road driving assessment (DriveABLE) and (ii) the association between minimal hepatic encephalopathy (MHE), in-office paper-pencil tools, and additional measures (e.g., frailty, depression, cognitive testing) with unsafe driving. METHODS: Patients were prospectively recruited from 2 tertiary care liver clinics. In-office tests and in-office and on-road assessments of driving competence were completed. The χ 2 test and 1-way analysis of variance were used to analyze differences among those with and without MHE. Logistic regression was used to evaluate predictors of an indeterminate/fail result on the in-office computerized driving assessment battery (DriveABLE Cognitive Assessment Tool [DCAT]). RESULTS: Eighty patients participated with a mean age of 57 years, 70% male, 75% Child-Pugh B/C, and 36% with a history of overt hepatic encephalopathy. Thirty percent met MHE criteria on both the psychometric hepatic encephalopathy score and the Stroop app tests. Only 2 patients (3%) were categorized as "unfit to drive" in the on-road driving test, one with MHE and the other without. Fifty-eight percent of the patients were scored as indeterminate/fail on the DCAT. This corresponded to a higher mean number of on-road driving errors (5.3 [SD 2.1] vs 4.2 [SD 1.6] in those who passed the DCAT, P = 0.01). Older age (odds ratio 1.3; confidence interval 1.1, 1.5; P = 0.001) and MHE by Stroop/psychometric hepatic encephalopathy score (odds ratio 11.0; confidence interval 2.3, 51.8; P = 0.002) were independently predictive of worse performance on the DCAT. DISCUSSION: Worse performance in in-office testing was associated with worse scores on a computerized driving assessment battery and more on-road driving errors, but in-office tools were insufficient to predict on-road driving failures. A diagnosis of MHE should not be used alone to restrict driving in patients with cirrhosis. At-risk patients require on-road driving tests under the supervision of driving regulatory agencies. Future studies should continue to refine and evaluate in-office or at-home testing to predict driving performance.

Serum IgG4 cut-off of 70 mg/dL is associated with a shorter time to cirrhosis decompensation and liver transplantation in primary sclerosing cholangitis patients.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an immune-mediated biliary disorder of unknown etiology with no effective treatment. The purpose of this study was to better prognosticate the development of cirrhosis, decompensation, and requirement for liver transplantation (LT) in PSC patients based on serum immunoglobulin G4 (IgG4) levels. METHODS: A retrospective chart review was conducted on PSC patients seen at the University of Alberta Hospital between 2002 and 2017. PSC patients were categorized as high IgG4 group (≥70 mg/dL) or normal IgG4 group (<70 mg/dL). Laboratory parameters, clinical characteristics, and outcomes were compared between the groups. RESULTS: One hundred and ten patients were followed over a mean period of 7.3 (SD 5) years. Seventy-two patients (66%) were male, the mean age at diagnosis of PSC was 35 (SD 15) years, and inflammatory bowel disease (IBD) was present in 80 patients (73%). High IgG4 levels were found in 37 patients (34%). PSC patients with high IgG4 had a shorter mean cholangitis-free survival time (5.3 versus 10.4 years, p = 0.02), cirrhosis-free survival time (8.7 versus 13.0 years, p = 0.02), and LT-free survival time (9.3 years versus 18.9 years, p <0.001). IgG4 ≥70 mg/dL was independently associated with liver decompensation and LT-free outcomes. A cut-off IgG4 value of ≥70 mg/dL performed better than a cut-off value of ≥140 mg/dL to predict time to LT (area under the curve [AUC] 0.68, p = 0.03, sensitivity 72%, specificity 78%). CONCLUSIONS: Serum IgG4 ≥70 mg/dL in PSC predicts a shorter time to cirrhosis decompensation and LT.

Longitudinal Changes in the Composition of the Penile Microbiome Are Associated With Circumcision Status, HIV and HSV-2 Status, Sexual Practices, and Female Partner Microbiome Composition.

Background: Penile microbiome composition has been associated with HSV-2 and HIV in men and with bacterial vaginosis (BV) and HSV-2 in female sex partners. This study sought to 1) characterize penile microbiome composition over a 1-year period and 2) identify factors associated with penile microbiome composition over time. Methods: This prospective study of community-recruited heterosexual couples in Kenya measured penile and vaginal microbiomes via 16S ribosomal RNA gene amplicon sequencing at 4 time points over 1 year (1, 6, and 12 months after baseline). We used longitudinal mixed-effects modeling to assess associated demographic, behavioral, and disease factors and changes in community type, meatal taxa with the highest mean relative abundance, and alpha and beta diversity measures. We estimated group-based trajectories to elucidate compositional trends. Results: Among 218 men with 740 observations, men had a median age of 26 years, 11.6% were living with HIV, and 46.1% were HSV-2 seropositive. We identified 7 penile community types that varied with circumcision status, female partner vaginal microbiome community state type (CST), condom use, and penile washing. Across varying analytic approaches, 50%-60% of men had stable penile microbiome compositions. Alpha diversity measures were lower for circumcised men and those who reported condom use; they were stable over time but higher if female partners had diverse CSTs or BV. BV was positively associated with the relative abundance of numerous individual penile taxa. The decreased Bray-Curtis similarity was more common for men with HSV-2, and HSV-2 was also associated with a lower relative abundance of Corynebacterium and Staphylococcus. Conclusions: Over a 1-year period, penile microbiome composition was stable for a substantial proportion of men and was influenced by men's circumcision status, sexual practices, female partner's vaginal CST and BV status, and men's HSV-2 status. In the female genital tract, a diverse CST is often associated with poorer health outcomes. Our results contribute toward understanding whether this framework extends to the penile microbiome and whether diversity and the associated penile microbiome compositions influence susceptibility or resilience to poorer health outcomes in men. Focusing on understanding how these factors influence the penile microbiome may lead to therapeutic avenues for reduced HSV-2 and BV infections in men and their female sex partners.