Diverse bacterial species contribute to antibiotic-associated diarrhoea and gastrointestinal damage

Objectives: Antibiotic-associated diarrhoea (AAD) caused by C. difficile is one of the most common nosocomial infections, however, little is known about infections related to antimicrobial use for pathogens other than C. difficile. We therefore aimed to provide insight into other bacterial causes of AAD, and how infection with these pathogens causes damage in the dysbiotic gut. Methods: Clinical isolates from C. difficile-negative AAD patients were whole genome sequenced for in silico analysis of potential virulence factors and antimicrobial resistance determinants. A mouse model of infection was developed to assess the capacity of these isolates to cause gastrointestinal damage, which was analysed by studying specific markers in the gastrointestinal mucosa of infected mice. Results: Several bacterial pathogens were isolated from patients with C. difficile-negative AAD. Each isolate showed the potential for virulence based on encoded virulence factors, as well as most showing antimicrobial resistance in vitro. Isolates of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were tested in the mouse model of infection, inducing damage primarily in the small intestine, affecting adherens junction integrity, cellular polarity, and cellular proliferation. Conclusions: Several pathogens of clinical importance other than C. difficile are able to cause gastrointestinal infection following antimicrobial-mediated dysbiosis. The virulence potential and multidrug resistance identified in these isolates illuminates the importance of further diagnostic screening in cases of C. difficile-negative AAD

Water quality modelling of the Mekong River basin: climate change and socioeconomics drive flow and nutrient flux changes to the Mekong Delta

The Mekong delta is recognised as one of the world's most vulnerable mega-deltas, being subject to a range of environmental pressures including sea level rise, increasing population, and changes in flows and nutrients from its upland catchment. With changing climate and socioeconomics there is a need to assess how the Mekong catchment will be affected in terms of the delivery of water and nutrients into the delta system. Here we apply the Integrated Catchment model (INCA) to the whole Mekong River Basin to simulate flow and water quality, including nitrate, ammonia, total phosphorus and soluble reactive phosphorus. The impacts of climate change on all these variables have been assessed across 24 river reaches ranging from the Himalayas down to the delta in Vietnam. We used the UK Met Office PRECIS regionally coupled climate model to downscale precipitation and temperature to the Mekong catchment. This was accomplished using the Global Circulation Model GFDL-CM to provide the boundary conditions under two carbon control strategies, namely representative concentration pathways (RCP) 4.5 and a RCP 8.5 scenario. The RCP 4.5 scenario represents the carbon strategy required to meet the Paris Accord, which aims to limit peak global temperatures to below a 2 °C rise whilst seeking to pursue options that limit temperature rise to 1.5 °C. The RCP 8.5 scenario is associated with a larger 3–4 °C rise. In addition, we also constructed a range of socio-economic scenarios to investigate the potential impacts of changing population, atmospheric pollution, economic growth and land use change up to the 2050s. Results of INCA simulations indicate increases in mean flows of up to 24%, with flood flows in the monsoon period increasing by up to 27%, but with increasing periods of drought up to 2050. A shift in the timing of the monsoon is also simulated, with a 4 week advance in the onset of monsoon flows on average. Decreases in nitrogen and phosphorus concentrations occur primarily due to flow dilution, but fluxes of these nutrients also increase by 5%, which reflects the changing flow, land use change and population changes

Alcohol Use Disorder and Recent Alcohol Use and HIV Viral Non-Suppression Among People Engaged in HIV Care in an Urban Clinic, 2014–2018

We estimated joint associations between having history of alcohol use disorder (AUD) (based on prior ICD-9/ICD-10 codes) and recent self-reported alcohol use and viral non-suppression (≥ 1 viral load measurement > 20 copies/mL in the same calendar year as alcohol consumption was reported) among patients on ART enrolled in routine care, 2014–2018, in an urban specialty clinic. Among 1690 patients, 26% had an AUD, 21% reported high-risk alcohol use, and 39% had viral non-suppression. Relative to person-years in which people without AUD reported not drinking, prevalence of viral non-suppression was higher in person-years when people with AUD reported drinking at any level; prevalence of viral non-suppression was not significantly higher in person-years when people with AUD reported not drinking or person-years when people without AUD reported drinking at any level. No level of alcohol use may be “safe” for people with a prior AUD with regard to maintaining viral suppression

Longitudinal analysis of alcohol use and intimate partner violence perpetration among men with HIV in northern Vietnam

Background: Alcohol use is a known risk factor for male-perpetrated intimate partner violence (IPV), although few studies have been conducted globally and among men with HIV (MWH). We estimated the longitudinal effects of alcohol use on IPV perpetration among MWH. Methods: This study is a secondary analysis of randomized controlled trial data among male and female antiretroviral treatment patients with hazardous alcohol use in Thai Nguyen, Vietnam. Analyses were restricted to male participants who were married/cohabitating (N = 313). Alcohol use was assessed as proportion days alcohol abstinent, heavy drinking, and alcohol use disorder (AUD) using the Timeline Followback and Mini International Neuropsychiatric Interview questionnaire. Multilevel modeling was used to estimate the effects of higher versus lower average alcohol use on IPV perpetration (between-person effects) and the effects of time-specific deviations in alcohol use on IPV perpetration (within-person effects). Results: Participants with higher average proportion days alcohol abstinent had decreased odds of IPV perpetration (adjusted Odds Ratio [aOR] = 0.43, p = 0.03) and those with higher average heavy drinking and AUD had increased odds of IPV perpetration (Heavy drinking: aOR = 1.05, p = 0.002; AUD: aOR = 4.74, p < 0.0001). Time-specific increases in proportion days alcohol abstinent were associated with decreased odds of IPV perpetration (aOR = 0.39, p = 0.02) and time-specific increases in AUD were associated with increased odds of IPV perpetration (aOR = 2.95, p = 0.001). Within-person effects for heavy drinking were non-significant. Conclusions: Alcohol use is associated with IPV perpetration among Vietnamese men with HIV. In this context, AUD and frequent drinking are stronger correlates of IPV perpetration as compared to heavy drinking

Effects of Two Alcohol Reduction Interventions on Depression and Anxiety Symptoms of ART Clients in Vietnam

Little is known about the potential mental health impacts of cognitive behavioral therapy and motivational interviewing interventions that focus on alcohol reduction among people with HIV (PWH). Our study aimed to assess the impact of two evidence-based alcohol reduction interventions on depression and anxiety symptoms of antiretroviral therapy (ART) clients with hazardous alcohol use. We conducted a secondary data analysis of data from a three-arm randomized controlled trial among ART clients in Thai Nguyen, Vietnam that evaluated the impacts of two alcohol reduction interventions in Vietnam. ART clients 18 years old or more with hazardous alcohol use (based on the Alcohol Use Disorders Identification Test-Consumption) were enrolled and randomized into one of three arms: Combined intervention, Brief intervention, and Standard of care (SOC). Symptoms of depression, measured with the Patient Health Questionnaire-9, and anxiety, measured with the Generalized Anxiety Disorder-7 scale, were assessed at baseline and 3, 6, and 12 months post-intervention. Generalized estimating equations were used to evaluate the effects of the interventions on depression and anxiety symptoms. The prevalence of depression and anxiety symptoms at baseline was 25.1% and 16.1%, respectively. Decreases in depression and anxiety symptoms were observed in all three arms from baseline to 12-month follow-up. There were no significant differences in depression and anxiety symptoms among participants receiving either intervention, relative to the SOC. Interventions with a dual focus on alcohol and mental health are needed to achieve more pronounced and sustainable improvements in depression and anxiety symptoms for PWH with hazardous alcohol use

The longitudinal association between depression, anxiety symptoms and HIV outcomes, and the modifying effect of alcohol dependence among ART clients with hazardous alcohol use in Vietnam

Introduction: Mental health disorders may negatively impact HIV outcomes, such as viral suppression (VS) and antiretroviral (ART) adherence among people with HIV (PWH) with hazardous alcohol use. This study evaluates the longitudinal association between depression, anxiety symptoms, VS and complete ART adherence among ART clients with hazardous alcohol use in Vietnam; and examines alcohol dependence as a modifier in this association. Methods: This was a secondary data analysis of a trial for hazardous drinking ART clients in Thai Nguyen, Vietnam. From March 2016 to May 2018, 440 ART clients with an Alcohol Use Disorders Identification Test-Concise (AUDIT-C) score ≥4 for men and ≥3 for women were enrolled. Individuals were randomized to either a combined intervention, a brief intervention or a standard of care. Data on sociodemographics, depression, anxiety symptoms, alcohol use, VS and ART adherence were collected at baseline, three, six, and twelve months. Generalized estimating equation models controlling for intervention exposure were used to estimate time-lagged associations. Risk ratios were estimated using Poisson regression with robust variance estimation. Results: The mean age of participants was 40.2. The majority was male (96.8%), had at least some secondary school education (85.0%) and had a history of injection drug use (80.9%). No overall effect of depression and anxiety symptoms on VS was observed. When stratified by time, increased anxiety symptoms at six months were associated with VS at 12 months (adjusted risk ratio (aRR) = 1.09; 95% CI 1.02 to 1.17). An increase in depression or anxiety symptoms was associated with a decreased probability of complete ART adherence (depression symptoms: aRR = 0.95; 95% CI: 0.91 to 0.99; anxiety symptoms: aRR = 0.93; 85% CI: 0.88 to 0.99). The negative effects of anxiety symptoms on ART adherence were stronger among participants with alcohol dependence, compared to those without. Conclusions: Depression and anxiety symptoms had no overall effect on VS, although they were associated with a lower probability of complete ART adherence. Interventions focusing on mental healthcare for PWH with hazardous alcohol use are needed, and integration of mental healthcare and alcohol reduction should be implemented in HIV primary care settings

Alcohol Use Patterns and Subsequent Sexual Behaviors Among Women, Men who have Sex with Men and Men who have Sex with Women Engaged in Routine HIV Care in the United States

Among people with HIV, alcohol use is associated with increased prevalence of sexual transmission behaviors. We examined associations between alcohol use in the prior year and sexual behaviors approximately six months later among 1857 women, 6752 men who have sex with men (MSM) and 2685 men who have sex with women (MSW). Any alcohol use was associated with increased risk of unsafe vaginal sex among women; anal sex and =>2 anal sex partners among MSM; and anal sex, =>2 anal or vaginal sex partners, and unsafe vaginal sex among MSW. In particular, among women >7 alcoholic drinks/week and among MSW =>5 alcoholic drinks/drinking day increased the likelihood of certain subsequent sexual behaviors. For all groups, especially women, the risk of sex under the influence of drugs/alcohol markedly increased with increases in quantity and frequency of alcohol consumption. These different patterns of drinking and sexual behaviors indicate the importance of tailored counseling messages to women, MSM and MSW

Do Symptoms of Depression Interact with Substance Use to Affect HIV Continuum of Care Outcomes?

Few studies examine how depression and substance use interact to affect HIV control. In 14,380 persons with HIV (PWH), we used logistic regression and generalized estimating equations to evaluate how symptoms of depression interact with alcohol, cocaine, opioid, and methamphetamine use to affect subsequent retention in care, maintaining an active prescription for ART, and consistent virologic suppression. Among PWH with no or mild depressive symptoms, heavy alcohol use had no association with virologic suppression (OR 1.00 [0.95–1.06]); among those with moderate or severe symptoms, it was associated with reduced viral suppression (OR 0.80 [0.74–0.87]). We found no interactions with heavy alcohol use on retention in care or maintaining ART prescription or with other substances for any outcome. These results highlight the importance of treating moderate or severe depression in PWH, especially with comorbid heavy alcohol use, and support multifaceted interventions targeting alcohol use and depression

Alcohol consumption upon direct-acting antiviral therapy for hepatitis C among persons with human immunodeficiency virus in the United States

Background: Direct-acting antivirals (DAA) are highly effective against hepatitis C virus (HCV) infection among persons with human immunodeficiency virus (PWH). However, alcohol use post-DAA treatment poses a continued threat to the liver. Whether the focus on liver health alone during HCV treatment can impact alcohol consumption is unclear. Therefore, we examined the change in alcohol use among HCV-coinfected PWH who received DAA therapy by non-addiction medical providers. Methods: In our longitudinal clinical cohort study, we identified HCV-coinfected PWH who received interferon-free DAA therapy between January 2014 and June 2019 in the Centers for AIDS Research Network of Integrated Clinical Systems. The Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) was the alcohol screening instrument. We used mixed-effects logistic regression models to estimate the longitudinal change in alcohol use upon DAA therapy. Results: Among 738 HCV-coinfected PWH, 339 (46 %) reported any alcohol use at the end of HCV treatment, including 113 (15 %) with high-risk use (i.e., AUDIT-C ≥3 for women, ≥4 for men). Concurrently, 280 (38 %) PWH noted active drug use, and 357 (48 %) were currently smoking. We observed no changes in the odds of any alcohol or high-risk alcohol use over time with DAA therapy. Findings were similar in the PWH subgroup with a history of alcohol use before DAA treatment. Conclusions: For PWH with HCV, alcohol use did not change following interferon-free DAA treatment by non-addiction medical providers. Thus, clinicians should consider integrating targeted alcohol use interventions into HCV care to motivate reduced alcohol consumption and safeguard future liver health

Gaia Early Data Release 3: The celestial reference frame (Gaia-CRF3)

Context. Gaia-CRF3 is the celestial reference frame for positions and proper motions in the third release of data from the Gaia mission, Gaia DR3 (and for the early third release, Gaia EDR3, which contains identical astrometric results). The reference frame is defined by the positions and proper motions at epoch 2016.0 for a specific set of extragalactic sources in the (E)DR3 catalogue. Aims. We describe the construction of Gaia-CRF3 and its properties in terms of the distributions in magnitude, colour, and astrometric quality. Methods. Compact extragalactic sources in Gaia DR3 were identified by positional cross-matching with 17 external catalogues of quasi-stellar objects (QSO) and active galactic nuclei (AGN), followed by astrometric filtering designed to remove stellar contaminants. Selecting a clean sample was favoured over including a higher number of extragalactic sources. For the final sample, the random and systematic errors in the proper motions are analysed, as well as the radio-optical offsets in position for sources in the third realisation of the International Celestial Reference Frame (ICRF3). Results. Gaia-CRF3 comprises about 1.6 million QSO-like sources, of which 1.2 million have five-parameter astrometric solutions in Gaia DR3 and 0.4 million have six-parameter solutions. The sources span the magnitude range G = 13-21 with a peak density at 20.6 mag, at which the typical positional uncertainty is about 1 mas. The proper motions show systematic errors on the level of 12 μas yr-1 on angular scales greater than 15 deg. For the 3142 optical counterparts of ICRF3 sources in the S/X frequency bands, the median offset from the radio positions is about 0.5 mas, but it exceeds 4 mas in either coordinate for 127 sources. We outline the future of Gaia-CRF in the next Gaia data releases. Appendices give further details on the external catalogues used, how to extract information about the Gaia-CRF3 sources, potential (Galactic) confusion sources, and the estimation of the spin and orientation of an astrometric solution