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

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

Development and validation of an electronic health records-based opioid use disorder algorithm by expert clinical adjudication among patients with prescribed opioids

Background: In the US, over 200 lives are lost from opioid overdoses each day. Accurate and prompt diagnosis of opioid use disorders (OUD) may help prevent overdose deaths. However, international classification of disease (ICD) codes for OUD are known to underestimate prevalence, and their specificity and sensitivity are unknown. We developed and validated algorithms to identify OUD in electronic health records (EHR) and examined the validity of OUD ICD codes. Methods: Through four iterations, we developed EHR-based OUD identification algorithms among patients who were prescribed opioids from 2014 to 2017. The algorithms and OUD ICD codes were validated against 169 independent “gold standard” EHR chart reviews conducted by an expert adjudication panel across four healthcare systems. After using 2014–2020 EHR for validating iteration 1, the experts were advised to use 2014–2017 EHR thereafter. Results: Of the 169 EHR charts, 81 (48%) were reviewed by more than one expert and exhibited 85% expert agreement. The experts identified 54 OUD cases. The experts endorsed all 11 OUD criteria from the Diagnostic and Statistical Manual of Mental Disorders-5, including craving (72%), tolerance (65%), withdrawal (56%), and recurrent use in physically hazardous conditions (50%). The OUD ICD codes had 10% sensitivity and 99% specificity, underscoring large underestimation. In comparison our algorithm identified OUD with 23% sensitivity and 98% specificity. Conclusions and relevance: This is the first study to estimate the validity of OUD ICD codes and develop validated EHR-based OUD identification algorithms. This work will inform future research on early intervention and prevention of OUD

RNAi targeting of rootworm Troponin I transcripts confers root protection in maize

Western corn rootworm, Diabrotica virgifera virgifera, is the major agronomically important pest of maize in the US Corn Belt. To augment the repertoire of the available dsRNA-based traits that control rootworm, we explored a potentially haplolethal gene target, wings up A (wupA), which encodes Troponin I. Troponin I, a component of the Troponin-Tropomyosin complex, is an inhibitory protein involved in muscle contraction. In situ hybridization showed that feeding on wupA-targeted dsRNAs caused systemic transcript knockdown in D. v. virgifera larvae. The knockdown of wupA transcript, and by extension Troponin I protein, led to deterioration of the striated banding pattern in larval body muscle and decreased muscle integrity. Additionally, the loss of function of the circular muscles surrounding the alimentary system led to significant accumulation of food material in the hind gut, which is consistent with a loss of peristaltic motion of the alimentary canal. In this study, we demonstrate that wupA dsRNA is lethal in D. v. virgifera larvae when fed via artificial diet, with growth inhibition of up to 50% within two days of application. Further, wupA hairpins can be stably expressed and detected in maize. Maize expressing wupA hairpins exhibit robust root protection in greenhouse bioassays, with several maize transgene integration events showing root protection equivalent to commercial insecticidal protein-expressing maize

HIT-COVID, a global database tracking public health interventions to COVID-19

The COVID-19 pandemic has sparked unprecedented public health and social measures (PHSM) by national and local governments, including border restrictions, school closures, mandatory facemask use and stay at home orders. Quantifying the effectiveness of these interventions in reducing disease transmission is key to rational policy making in response to the current and future pandemics. In order to estimate the effectiveness of these interventions, detailed descriptions of their timelines, scale and scope are needed. The Health Intervention Tracking for COVID-19 (HIT-COVID) is a curated and standardized global database that catalogues the implementation and relaxation of COVID-19 related PHSM. With a team of over 200 volunteer contributors, we assembled policy timelines for a range of key PHSM aimed at reducing COVID-19 risk for the national and first administrative levels (e.g. provinces and states) globally, including details such as the degree of implementation and targeted populations. We continue to maintain and adapt this database to the changing COVID-19 landscape so it can serve as a resource for researchers and policymakers alike

Computational Drug Repurposing: Current Trends

Biomedical discovery has been reshaped upon the exploding digitization of data which can be retrieved from a number of sources, ranging from clinical pharmacology to cheminformatics-driven databases. Now, supercomputing platforms and publicly available resources such as biological, physicochemical, and clinical data, can all be integrated to construct a detailed map of signaling pathways and drug mechanisms of action in relation to drug candidates. Recent advancements in computer-aided data mining have facilitated analyses of 'big data' approaches and the discovery of new indications for pre-existing drugs has been accelerated. Linking gene-phenotype associations to predict novel drug-disease signatures or incorporating molecular structure information of drugs and protein targets with other kinds of data derived from systems biology provide great potential to accelerate drug discovery and improve the success of drug repurposing attempts. In this review, we highlight commonly used computational drug repurposing strategies, including bioinformatics and cheminformatics tools, to integrate large-scale data emerging from the systems biology, and consider both the challenges and opportunities of using this approach. Moreover, we provide successful examples and case studies that combined various in silico drug-repurposing strategies to predict potential novel uses for known therapeutics