Considerations for the Identification and Conveyance of Clinical Pathology Findings in Preclinical Toxicity Studies: Results From the 9th ESTP International Expert Workshop.

The European Society of Toxicologic Pathology (ESTP) organized a panel of 24 international experts from many fields of toxicologic clinical pathology (e.g., industry, academia, and regulatory) that came together in 2021 to align the use of terminology to convey the importance of clinical pathology findings in preclinical toxicity studies. An additional goal consisted of how to identify important findings in standard and nonstandard clinical pathology associated endpoints. This manuscript summarizes the information and opinions discussed and shared at the ninth ESTP International Expert Workshop, April 5 to 6, 2022. In addition to terminology usage, the workshop considered topics related to the identification and conveyance of the importance of test item-related findings. These topics included sources of variability, comparators, statistics, reporting, correlations to other study data, nonstandard biomarkers, indirect/secondary findings, and an overall weight-of-evidence approach.

Exploring Comprehension Strategies of Modular Process Models: A Combined Eye-Tracking and Concurrent Think-Aloud Study.

The study of complex process models often encounters challenges in terms of comprehensibility. This paper explores using modularization as a strategy to mitigate such challenges, notably the reduction in complexity. Previous research has delved into the comprehensibility of modularized process models, yet an unresolved question about the cognitive factors at play during their comprehension still needs to be answered. Addressing the latter, the paper presents findings from an innovative study combining eye-tracking and concurrent think-aloud techniques involving 25 participants. The study aimed to comprehend how individuals comprehend process models when presented in three different modular formats: flattened process models, models with grouped elements, and models with subprocesses. The results shed light on varying comprehension strategies employed by participants when navigating through these modularized process models. The paper concludes by suggesting avenues for future research guided by these insights.

Modeling health and well-being measures using ZIP code spatial neighborhood patterns.

Individual-level assessment of health and well-being permits analysis of community well-being and health risk evaluations across several dimensions of health. It also enables comparison and rankings of reported health and well-being for large geographical areas such as states, metropolitan areas, and counties. However, there is large variation in reported well-being within such large spatial units underscoring the importance of analyzing well-being at more granular levels, such as ZIP codes. In this paper, we address this problem by modeling well-being data to generate ZIP code tabulation area (ZCTA)-level rankings through spatially informed statistical modeling. We build regression models for individual-level overall well-being index and scores from five subscales (Physical, Financial, Social, Community, Purpose) using individual-level demographic characteristics as predictors while including a ZCTA-level spatial effect. The ZCTA neighborhood information is incorporated by using a graph Laplacian matrix; this enables estimation of the effect of a ZCTA on well-being using individual-level data from that ZCTA as well as by borrowing information from neighboring ZCTAs. We deploy our model on well-being data for the U.S. states of Massachusetts and Georgia. We find that our model can capture the effects of demographic features while also offering spatial effect estimates for all ZCTAs, including ones with no observations, under certain conditions. These spatial effect estimates provide community health and well-being rankings of ZCTAs, and our method can be deployed more generally to model other outcomes that are spatially dependent as well as data from other states or groups of states.

A Fall Prevention Feasibility Trial for People With HIV and Alcohol Use.

Alcohol contributes to higher fall risk in people living with HIV (PLWH), yet fall prevention trials for PWH with alcohol use are lacking. To assess the feasibility of conducting a randomized controlled trial of a 10-week online fall prevention intervention tailored for PLWH with alcohol use. The intervention consisted of weekly virtual group discussions, individual phone check-ins, and home exercises. Of those eligible, 53.5% (23/43) enrolled (12 to the intervention and 11 to control). Mean age was 58 years; 82.6% had a past 6-month fall; 65.2% had alcohol use disorder; and 95.7% completed postintervention assessments. The intervention was highly rated (Client Satisfaction Questionnaire-8 score M = 30.4, SD = 1.6) with a wide range of group and individual phone session attendance. Preliminary analyses suggest the intervention may reduce the odds of falling and alcohol use frequency. Findings support the feasibility of a larger randomized trial. ClinicalTrials.gov Identifier: NCT04804579.

A fall prevention feasibility trial for people with HIV and alcohol useAlcohol contributes to higher fall risk in people living with HIV (PLWH), yet fall prevention studies for PLWH with alcohol use are lacking. We conducted a 10-week online fall prevention intervention for PLWH (n = 23) with recent alcohol use to assess if the intervention was feasible and acceptable for PLWH. The intervention consisted of weekly virtual group discussions and individual phone check-ins with an occupational therapist and a customized home exercise program. The mean age was 58 years. Almost all fell in the past 6 months (82.6%), had impaired physical functioning (91.3%), and had alcohol use disorder (65.2%). Participants reported high intervention satisfaction. Preliminary analyses suggest that the intervention may reduce the odds of falling and alcohol use frequency. Findings support the feasibility of an online fall prevention intervention study for PLWH.

Pilot RCT comparing low-dose naltrexone, gabapentin and placebo to reduce pain among people with HIV with alcohol problems.

BACKGROUND: To estimate the effects on pain of two medications (low-dose naltrexone and gabapentin) compared to placebo among people with HIV (PWH) with heavy alcohol use and chronic pain. METHODS: We conducted a pilot, randomized, double-blinded, 3-arm study of PWH with chronic pain and past-year heavy alcohol use in 2021. Participants were recruited in St. Petersburg, Russia, and randomized to receive daily low-dose naltrexone (4.5mg), gabapentin (up to 1800mg), or placebo. The two primary outcomes were change in self-reported pain severity and pain interference measured with the Brief Pain Inventory from baseline to 8 weeks. RESULTS: Participants (N = 45, 15 in each arm) had the following baseline characteristics: 64% male; age 41 years (SD±7); mean 2 (SD±4) heavy drinking days in the past month and mean pain severity and interference were 3.2 (SD±1) and 3.0 (SD±2), respectively. Pain severity decreased for all three arms. Mean differences in change in pain severity for gabapentin vs. placebo, and naltrexone vs. placebo were -0.27 (95% confidence interval [CI] -1.76, 1.23; p = 0.73) and 0.88 (95% CI -0.7, 2.46; p = 0.55), respectively. Pain interference decreased for all three arms. Mean differences in change in pain interference for gabapentin vs. placebo, and naltrexone vs. placebo was 0.16 (95% CI -1.38, 1.71; p = 0.83) and 0.40 (95% CI -1.18, 1.99; p = 0.83), respectively. CONCLUSION: Neither gabapentin nor low-dose naltrexone appeared to improve pain more than placebo among PWH with chronic pain and past-year heavy alcohol use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT4052139).

Self-medication of pain and discomfort with alcohol and other substances by people with HIV infection and substance use disorder: preliminary findings from a secondary analysis.

There is a limited literature regarding factors associated with self-medication of pain and discomfort using alcohol, non-prescription substances or overuse of prescription medications among people living with Human Immunodeficiency Virus (HIV). This cross-sectional analysis used data from the Boston ARCH Cohort among participants with HIV infection and a history of alcohol or other substance use. Among 248 participants, 37% were female, 50% Black, 25% Latinx; 36% reported fair to poor health and 89% had CD4 cell counts >200/mm3. Half reported self-medication and of those, 8.8% reported doing so only with alcohol, 48.8% only with other substances and 42.4% with both alcohol and other substances. Those reporting self-medication were significantly (p < .05) younger (mean 47 vs 50 years), less employed (11% vs 21%), and less likely to have HIV viral suppression (60% vs. 80%). Depression, anxiety, and HIV symptoms were associated with significantly greater odds of self-medicating, as were substance dependence, recent injection substance use, heavy alcohol use, cocaine use, opioid use, sedative use, and cannabis use. Self-medication, highly prevalent and associated with worse mental health symptoms, greater substance use, and lesser HIV disease control, should be explored by HIV clinicians caring for people who use substances.

Alcohol Consumption and Illicit Drug Use: Associations With Fall, Fracture, and Acute Health Care Utilization Among People With HIV Infection.

BACKGROUND: Given alcohol and/or other drug (AOD) use occurs among people with HIV (PWH), we examined its association with falls and fall-related outcomes and whether frailty moderates the association. SETTING: Northeastern US city. METHODS: We analyzed an observational cohort of PWH with current or past AOD use. Alcohol measures were any past 14-day heavy use, average alcohol/day, and days with heavy use. Drug use measures were past 30-day illicit use of cocaine, opioids, and sedatives. Repeated cross-sectional associations were estimated with separate multivariable generalized estimating equation regression models for each fall-related outcome. RESULTS: Among PWH (n = 251; mean age 52 [SD = 10]), 35% reported heavy alcohol use, 24% cocaine, 16% illicit opioids, 13% illicit sedatives, and 35% any fall; 27% were frail. Heavy alcohol use was associated with a fall (AOR = 1.49, 95% CI: 1.08 to 2.07), multiple falls (AOR = 1.55 95% CI: 1.10 to 2.19), and fall/fracture-related emergency department visit or hospitalization (AOR = 1.81, 95% CI: 1.10 to 2.97). Higher average alcohol/day and more heavy drinking days were associated with multiple falls. Illicit sedative use was associated with a fall, multiple falls, and emergency department visit/hospitalization and opioid use with fracture. Frailty moderated the association of heavy alcohol use and a fall (AOR = 2.26, 95% CI: 1.28 to 4.01 in those frail) but not in those not frail. CONCLUSION: The effect of AOD use on falls and fall-related outcomes was most pronounced with alcohol, particularly among frail PWH. Heavy alcohol, illicit sedative, and illicit opioid use are high-priority targets for preventing falls and fall-related consequences for PWH.

Understanding Medication Nonadherence in Crohn's Disease Patients: A Qualitative Evaluation.

BACKGROUND: Immune-modifying medications are widely available and recognized as valuable by most gastroenterologists. However, approximately 40% of patients with Crohn's disease (CD) do not comply with regimens using these medications, resulting in complications, hospitalization, and surgeries. We sought to identify factors that motivate adherence or nonadherence with medication recommendations for CD. METHODS: We conducted qualitative interviews with patients living with CD who were identified as adherent or nonadherent to immune-modifying medication recommendations by their treating gastroenterologist. Semistructured interview guides were developed based on an established framework for understanding health behaviors. We conducted content analysis of the resulting qualitative data using an inductive-deductive approach to identify emergent themes that influence medication decision-making. RESULTS: Twenty-five patients with CD completed interviews for this study. Interviews were independently coded and analyzed for thematic content. Two broad domains emerged comprising (1) themes reflected in the Theoretical Domains Framework and (2) novel themes specific to medication decision-making in CD. Adherent patients conveyed a sense of trust in science and healthcare provider expertise, while nonadherent patients were more likely to express beliefs in their ability to self-manage CD, concern about risks associated with medication, and a general ambivalence to treatment. CONCLUSIONS: There are clear cognitive, behavioral, and relational factors that guide patients' medication-related decision-making. Several of the factors share features of other behavioral change and decision-making processes, while others are specific to the experience of patients with CD. A fuller understanding of these factors is essential to developing effective behavioral interventions to improve adherence to evidence-based treatment recommendations.

This study identified the determinants of medication adherence in a sample of patients receiving treatment for Crohn's disease. A total of 13 determinants across 2 domains were identified as contributing to patient decisions regarding the use of immune-modifying medications.

Transgenic ferret models define pulmonary ionocyte diversity and function.

Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans1,2, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-CreERT2::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-CreERT2::CFTRL/L). By comparing these models with cystic fibrosis ferrets3,4, we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity-leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, FOXI1-KO and FOXI1-CreERT2::CFTRL/L ferrets. These processes are regulated by CFTR-dependent ionocyte transport of Cl- and HCO3-. Single-cell transcriptomics and in vivo lineage tracing revealed three subtypes of pulmonary ionocytes and a FOXI1-lineage common rare cell progenitor for ionocytes, tuft cells and neuroendocrine cells during airway development. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of cystic fibrosis airway disease. These studies provide a road map for using conditional genetics in the first non-rodent mammal to address gene function, cell biology and disease processes that have greater evolutionary conservation between humans and ferrets.

Video Intervention and Goals-of-Care Documentation in Hospitalized Older Adults: The VIDEO-PCE Randomized Clinical Trial.

Importance: Despite the benefits of goals-of-care (GOC) communication, many hospitalized individuals never communicate their goals or preferences to clinicians. Objective: To assess whether a GOC video intervention delivered by palliative care educators (PCEs) increased the rate of GOC documentation. Design, Setting, and Participants: This pragmatic, stepped-wedge cluster randomized clinical trial included patients aged 65 years or older admitted to 1 of 14 units at 2 urban hospitals in New York and Boston from July 1, 2021, to October 31, 2022. Intervention: The intervention involved PCEs (social workers and nurses trained in GOC communication) facilitating GOC conversations with patients and/or their decision-makers using a library of brief, certified video decision aids available in 29 languages. Patients in the control period received usual care. Main Outcome and Measures: The primary outcome was GOC documentation, which included any documentation of a goals conversation, limitation of life-sustaining treatment, palliative care, hospice, or time-limited trials and was obtained by natural language processing. Results: A total of 10 802 patients (mean [SD] age, 78 [8] years; 51.6% male) were admitted to 1 of 14 hospital units. Goals-of-care documentation during the intervention phase occurred among 3744 of 6023 patients (62.2%) compared with 2396 of 4779 patients (50.1%) in the usual care phase (P < .001). Proportions of documented GOC discussions for Black or African American individuals (865 of 1376 [62.9%] vs 596 of 1125 [53.0%]), Hispanic or Latino individuals (311 of 548 [56.8%] vs 218 of 451 [48.3%]), non-English speakers (586 of 1059 [55.3%] vs 405 of 863 [46.9%]), and people living with Alzheimer disease and related dementias (520 of 681 [76.4%] vs 355 of 570 [62.3%]) were greater during the intervention phase compared with the usual care phase. Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of older adults, a GOC video intervention delivered by PCEs resulted in higher rates of GOC documentation compared with usual care, including among Black or African American individuals, Hispanic or Latino individuals, non-English speakers, and people living with Alzheimer disease and related dementias. The findings suggest that this form of patient-centered care delivery may be a beneficial decision support tool. Trial Registration: ClinicalTrials.gov Identifier: NCT04857060.

Association between resilience promotion factors during childhood and risk of drug use disorder during adulthood.

Few studies have been conducted on the relationship between "outside-residing" resilience characteristics and the risk of developing drug use disorder later in life. These characteristics include responsive and caring parenting, household routines involving regular family meals and bedtime routines, social support from peers, participation in organized activities, and religious service attendance. We quantified the association between these resilience promotion factors during childhood and the risk of developing criteria for drug use disorder during adulthood using data from a retrospective cohort study of 618 adults born in Massachusetts during 1969-1983, including those with adverse childhood experiences (ACEs). Self-administered questionnaires gathered information on criteria for drug use disorder, ACEs, and family and community resilience promotion factors. Compared to individuals with "low" numbers of resilience promotion factors, 30% (95% CI: 0.5-0.9) and 50% reductions (95% CI: 0.4-0.8) in the risk of developing one or more criteria for drug use disorder were observed among those with "moderate" and "high" numbers of resilience factors, respectively (p value for trend=0.003). Overall, family factors were associated with greater risk reductions than comparable numbers of community factors. Among individuals with ACEs, a "high" number of family factors but not community factors were associated with a reduction in risk (RR:0.6, 95% CI:0.4-1.0 for family factors, RR:1.0, 95% CI:0.5-1.8 for community factors). These results suggest that the risk of developing criteria for drug use disorder decreases in a dose-response fashion according to the number of "outside-residing" resilience promotion factors during childhood, and that family factors are associated with greater risk reductions than community factors, particularly among individuals with ACEs. Coordinated prevention efforts at the family and community level are recommended to reduce the risk of this important societal problem.

Exploring the usability of an internet-based intervention and its providing eHealth platform in an eye-tracking study.

The proliferation of online eHealth has made it much easier for users to access healthcare services and interventions from the comfort of their own homes. This study looks at how well one such platform-eSano-performs in terms of user experience when delivering mindfulness interventions. In order to assess usability and user experience, several tools such as eye-tracking technology, think-aloud sessions, a system usability scale questionnaire, an application questionnaire, and post-experiment interviews were employed. Participants were evaluated while they accessed the first module of the mindfulness intervention provided by eSano to measure their interaction with the app, and their level of engagement, and to obtain feedback on both the intervention and its overall usability. The results revealed that although users generally rated their experience with the app positively in terms of overall satisfaction, according to data collected through the system usability scale questionnaire, participants rated the first module of the mindfulness intervention as below average. Additionally, eye-tracking data showed that some users skipped long text blocks in favor of answering questions quickly while others spent more than half their time reading them. Henceforth, recommendations were put forward to improve both the usability and persuasiveness of the app-such as incorporating shorter text blocks and more engaging interactive elements-in order to raise adherence rates. Overall findings from this study provide valuable insights into how users interact with the eSano's participant app which can be used as guidelines for the future development of more effective and user-friendly platforms. Moreover, considering these potential improvements will help foster more positive experiences that promote regular engagement with these types of apps; taking into account emotional states and needs that vary across different age groups and abilities. Supplementary Information: The online version contains supplementary material available at 10.1007/s12652-023-04635-4.

Effectiveness of an Immersive Telemedicine Platform for Delivering Diabetes Medical Group Visits for African American, Black and Hispanic, or Latina Women With Uncontrolled Diabetes: The Women in Control 2.0 Noninferiority Randomized Clinical Trial.

BACKGROUND: Medically underserved people with type 2 diabetes mellitus face limited access to group-based diabetes care, placing them at risk for poor disease control and complications. Immersive technology and telemedicine solutions could bridge this gap. OBJECTIVE: The purpose of this study was to compare the effectiveness of diabetes medical group visits (DMGVs) delivered in an immersive telemedicine platform versus an in-person (IP) setting and establish the noninferiority of the technology-enabled approach for changes in hemoglobin A1c (HbA1c) and physical activity (measured in metabolic equivalent of task [MET]) at 6 months. METHODS: This study is a noninferiority randomized controlled trial conducted from February 2017 to December 2019 at an urban safety net health system and community health center. We enrolled adult women (aged ≥18 years) who self-reported African American or Black race or Hispanic or Latina ethnicity and had type 2 diabetes mellitus and HbA1c ≥8%. Participants attended 8 weekly DMGVs, which included diabetes self-management education, peer support, and clinician counseling using a culturally adapted curriculum in English or Spanish. In-person participants convened in clinical settings, while virtual world (VW) participants met remotely via an avatar-driven, 3D VW linked to video teleconferencing. Follow-up occurred 6 months post enrollment. Primary outcomes were mean changes in HbA1c and physical activity at 6 months, with noninferiority margins of 0.7% and 12 MET-hours, respectively. Secondary outcomes included changes in diabetes distress and depressive symptoms. RESULTS: Of 309 female participants (mean age 55, SD 10.6 years; n=195, 63% African American or Black; n=105, 34% Hispanic or Latina; n=151 IP; and n=158 in VW), 207 (67%) met per-protocol criteria. In the intention-to-treat analysis, we confirmed noninferiority for primary outcomes. We found similar improvements in mean HbA1c by group at 6 months (IP: -0.8%, SD 1.9%; VW: -0.5%, SD 1.8%; mean difference 0.3, 97.5% CI -∞ to 0.3; P<.001). However, there were no detectable improvements in physical activity (IP: -6.5, SD 43.6; VW: -9.6, SD 44.8 MET-hours; mean difference -3.1, 97.5% CI -6.9 to ∞; P=.02). The proportion of participants with significant diabetes distress and depressive symptoms at 6 months decreased in both groups. CONCLUSIONS: In this noninferiority randomized controlled trial, immersive telemedicine was a noninferior platform for delivering diabetes care, eliciting comparable glycemic control improvement, and enhancing patient engagement, compared to IP DMGVs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02726425; https://clinicaltrials.gov/ct2/show/NCT02726425.

Testing the validity and reliability of the Person-Centered Contraceptive Counseling (PCCC) Performance Measure in a Real-World Contraceptive Access Program.

OBJECTIVES: To validate the Person-Centered Contraceptive Counseling (PCCC) patient-reported outcome performance measure and assess for differences by sociodemographic attributes using survey data from a multistate contraceptive access program. STUDY DESIGN: This analysis explored internal reliability and construct validity of the PCCC using survey data from 1413 patients who visited 15 health centers in Washington state and Massachusetts that had partnered with Upstream USA. RESULTS: Multiple psychometric indicators provided evidence of reliability and validity. Significant associations between the highest PCCC rating and conceptually-related survey questions (i.e., experience with bias/coercion and shared decision-making) provided further evidence of construct validity. CONCLUSIONS: Our findings demonstrate that the PCCC is valid and reliable. The results also highlight differences in experience of care by patient-reported race and ethnicity, income level, and language.

Farmers Supporting Farmers: Livestock Auctions as Spaces to Reconstruct Occupational Community and Counter Mental Health Issues.

Social isolation within agricultural communities is prevalent within the United Kingdom (UK). Along with other social and economic determinants, social isolation is considered to be a contributing factor towards the high rates of mental health issues experienced among people working in agriculture. The livestock auction mart is one of the remaining spaces upon which many livestock farmers rely for consistent social interaction and to experience community, both determinants proven to improve physical and mental health. However, the importance of the social contribution of livestock auction marts to farmer wellbeing appears rarely in associated literature. The aims of this study, therefore, were i) to determine levels of isolation experienced by livestock farmers who attend auction marts and ii) to identify the role of the mart as a system of social support, with an emphasis on the informal support system attendees provide for one another. Findings from 90 qualitative interviews demonstrate that the auction mart is an important social site where occupational community and identity can be produced and reproduced for all attending stakeholders, positively impacting upon mental health and wellbeing. The strength of the occupational community among livestock farmers should be considered as a key element among a basket of options approach in the development of support interventions, and as a pathway to negotiating barriers to both help-seeking behaviors and reaching the hard-to-reach.

Impact of alcohol use disorder severity on human immunodeficiency virus (HIV) viral suppression and CD4 count in three international cohorts of people with HIV.

BACKGROUND: Alcohol use has been linked to worse human immunodeficiency virus (HIV) immunologic/virologic outcomes, yet few studies have explored the effects of alcohol use disorder (AUD). This study assessed whether AUD severity is associated with HIV viral suppression and CD4 count in the three cohorts of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium. METHODS: People with HIV (PWH) in Uganda (n = 301), Russia (n = 400), and Boston (n = 251), selected in-part based on their alcohol use, were included in analyses. Logistic and linear regressions were used to assess the cross-sectional associations between AUD severity (number of DSM-5 diagnostic criteria) and (1) HIV viral suppression, and (2) CD4 count (cells/mm3 ) adjusting for covariates. Analyses were conducted separately by site. RESULTS: The proportion of females was 51% (Uganda), 34% (Russia), and 33% (Boston); mean age (SD) was 40.7 (9.6), 38.6 (6.3), and 52.1 (10.5), respectively. All participants in Uganda and all but 27% in Russia and 5% in Boston were on antiretroviral therapy. In Uganda, 32% met criteria for AUD, 92% in Russia, and 43% in Boston. The mean (SD) number of AUD criteria was 1.6 (2.4) in Uganda, 5.6 (3.3) in Russia, and 2.4 (3.1) in Boston. Most participants had HIV viral suppression (Uganda 92%, Russia 57%, Boston 87%); median (IQR) CD4 count was 673 (506, 866), 351 (201, 542), and 591 (387, 881), respectively. In adjusted models, there were no associations between AUD severity and HIV viral suppression: adjusted odds ratios (AOR) (95%CI) per 1 additional AUD criterion in Uganda was 1.08 (0.87, 1.33); Russia 0.98 (0.92, 1.04); and Boston 0.95 (0.84, 1.08) or CD4 count: mean difference (95%CI) per 1 additional criterion: 5.78 (-7.47, 19.03), -3.23 (-10.91, 4.44), and -8.18 (-24.72, 8.35), respectively. CONCLUSIONS: In three cohorts of PWH, AUD severity was not associated with HIV viral suppression or CD4 count. PWH with AUD in the current era of antiretroviral therapy can achieve virologic control.

Polysubstance Use Patterns Associated With HIV Disease Severity Among Those With Substance Use Disorders: A Latent Class Analysis.

OBJECTIVE: Polysubstance use is common among people with HIV infection (PWH) and with substance use disorder (SUD), but its effects are understudied. We aimed to identify polysubstance use patterns over time and assess their associations with HIV disease severity. METHOD: In 233 PWH with current or past SUD, latent class analysis identified polysubstance use patterns based on the Alcohol Use Disorders Identification Test-Consumption and past-30-day use of cannabis, cocaine, opioids, and tranquilizers at baseline. We categorized changes in use patterns and tested associations between those changes and CD4 count and HIV viral suppression at 12 months in linear and logistic regressions. RESULTS: Three patterns were identified at baseline: 18% did not use any substance (NONE--a priori defined); 63% used mostly cannabis and alcohol (CA); and 19% used opioids along with other drugs, including cocaine, tranquilizers, cannabis, and alcohol (MULTI). At 12 months, 40% moved from a high to a lower substance use class (MULTI to CA, either to NONE) or remained as NONE, 43% were in CA both times and 17% increased (NONE to CA, either to MULTI) or remained as MULTI. The adjusted mean CD4 count (for baseline covariates and baseline CD4 count) was significantly lower among participants increasing or remaining in MULTI (523, 95% CI [448, 598], cells/mm3) compared with those who decreased/abstained throughout (607, 95% CI [552, 663], p = .02). No significant difference was observed for HIV viral suppression. CONCLUSIONS: We identified distinct polysubstance use patterns among PWH with SUD: cannabis/alcohol and opioids with alcohol and other drugs. Changes over time toward fewer substances/no use were associated with lower HIV disease severity based on CD4 count but not based on HIV viral suppression.

Recruitment of sexual minority and heterosexual colorectal cancer survivors through US cancer registries.

PURPOSE: Describe the process, outcomes, and costs of cancer registry recruitment and enrollment of sexual minority and heterosexual non-metastatic colorectal cancer survivors into an observational survivorship study. METHODS: We recruited stage I-III colorectal cancer survivors from four US cancer registries. Potential participants were screened for eligibility, and all eligible sexual minority and every 10th heterosexual survivor was invited to participate in a 45-min telephone interview. RESULTS: We mailed study packets to 17,855 individuals and obtained 6370 screening surveys of presumed eligible individuals. After screening, there were 182 eligible sexual minority and 5568 eligible heterosexual survivors. Of the 719 invited survivors, 127 sexual minority and 353 heterosexual individuals participated in the interview. There were some small differences in personal and neighborhood sociodemographic characteristics for the survivors who screened eligible and completed the interview relative to the registry sample. The per-participant direct costs were about $40, $120, and $1425 in the registry, screened eligible, and interviewed samples, respectively. CONCLUSIONS: Although we did not observe substantial selection biases, the costs of enrolling a representative sample were high. IMPLICATIONS FOR CANCER SURVIVORS: Inclusion of sexual orientation and gender identity as standard demographic questions in cancer registries is needed for reliable and cost-efficient monitoring of population health.

Associations of Country-Specific and Sociodemographic Factors With Self-Reported COVID-19-Related Symptoms: Multivariable Analysis of Data From the CoronaCheck Mobile Health Platform.

BACKGROUND: The COVID-19 symptom-monitoring apps provide direct feedback to users about the suspected risk of infection with SARS-CoV-2 and advice on how to proceed to prevent the spread of the virus. We have developed the CoronaCheck mobile health (mHealth) platform, the first free app that provides easy access to valid information about the risk of infection with SARS-CoV-2 in English and German. Previous studies have suggested that the clinical characteristics of individuals infected with SARS-CoV-2 vary by age, gender, and viral variant; however, potential differences between countries have not been adequately studied. OBJECTIVE: The aim of this study is to describe the characteristics of the users of the CoronaCheck mHealth platform and to determine country-specific and sociodemographic associations of COVID-19-related symptoms and previous contacts with individuals infected with COVID-19. METHODS: Between April 8, 2020, and February 3, 2022, data on sociodemographic characteristics, symptoms, and reports of previous close contacts with individuals infected with COVID-19 were collected from CoronaCheck users in different countries. Multivariable logistic regression analyses were performed to examine whether self-reports of COVID-19-related symptoms and recent contact with a person infected with COVID-19 differed between countries (Germany, India, South Africa), gender identities, age groups, education, and calendar year. RESULTS: Most app users (N=23,179) were from Germany (n=8116, 35.0%), India (n=6622, 28.6%), and South Africa (n=3705, 16.0%). Most data were collected in 2020 (n=19,723, 85.1%). In addition, 64% (n=14,842) of the users were male, 52.1% (n=12,077) were ≥30 years old, and 38.6% (n=8953) had an education level of more than 11 years of schooling. Headache, muscle pain, fever, loss of smell, loss of taste, and previous contacts with individuals infected with COVID-19 were reported more frequently by users in India (adjusted odds ratios [aORs] 1.3-8.3, 95% CI 1.2-9.2) and South Africa (aORs 1.1-2.6, 95% CI 1.0-3.0) than those in Germany. Cough, general weakness, sore throat, and shortness of breath were more frequently reported in India (aORs 1.3-2.6, 95% CI 1.2-2.9) compared to Germany. Gender-diverse users reported symptoms and contacts with confirmed COVID-19 cases more often compared to male users. CONCLUSIONS: Patterns of self-reported COVID-19-related symptoms and awareness of a previous contact with individuals infected with COVID-19 seemed to differ between India, South Africa, and Germany, as well as by gender identity in these countries. Viral symptom-collecting apps, such as the CoronaCheck mHealth platform, may be promising tools for pandemics to support appropriate assessments. Future mHealth research on country-specific differences during a pandemic should aim to recruit representative samples.

(Thio)urea Containing Chiral Ammonium Salt Catalysts.

(Thio)-urea-containing bifunctional quaternary ammonium salts emerged as powerful non-covalently interacting organocatalysts over the course of the last decade. The most commonly employed catalysts in this field are either based on Cinchona alkaloids, α-amino acids, or trans-cyclohexane-1,2-diamine. Our group has been heavily engaged in the design and use of such catalysts, i. e. trans-cyclohexane-1,2-diamine-based ones for around 10 years now, and it is therefore the intention of this short personal account to provide an overview of the, at least in our opinion, most significant and pioneering achievements in this field by looking on catalyst design and asymmetric method development, with a special focus on our own contributions.