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Background: Tuberculosis (TB) remains a major plague of humanity. People with TB (PWTB) are commonly anemic. Here, we assessed whether the severity of anemia in PWTB prior to anti-TB treatment (ATT) was a risk factor for an unfavorable outcome. Methods: Patients ≥ 18 years old with culture-confirmed drug-susceptible pulmonary TB enrolled between 2015 and 2019 in a multi-center Brazilian cohort were followed for up to 24 months and classified according to anemia severity (mild, moderate, and severe), based on hemoglobin levels. A multinomial logistic regression model was employed to assess whether anemia was associated with unfavorable outcome (death, failure, loss to follow-up, regimen modification or relapse), compared to treatment success (cure or treatment completion). Results: Among 786 participants who met inclusion criteria, 441 (56 %) were anemic at baseline. Patients with moderate/severe anemia were more HIV-seropositive, as well as more symptomatic and had higher frequencies of unfavorable outcomes compared to the other groups. Moderate/severe anemia (adjusted OR [aOR]: 7.80, 95 %CI:1.34–45.4, p = 0.022) was associated with death independent of sex, age, BMI, HIV and glycemic status. Conclusion: Moderate/severe anemia prior to ATT was a significant risk factor for death. Such patients should be closely monitored given the high risk of unfavorable ATT outcomes.

Objectives: More men than women develop and die of tuberculosis (TB). Fewer data exist on sex differences in latent TB infection (LTBI). We assessed for potential sex differences in LTBI acquisition among close TB contacts. Methods: Regional Prospective Observational Research for TB-Brazil is an observational multi-center cohort of individuals with culture-confirmed pulmonary TB and their close contacts. Participants were enrolled from five sites in Brazil from June 2015 - June 2019. Close contacts were followed for 24 months after enrollment, with LTBI defined as a positive interferon-γ release assay (IGRA; QuantiFERON 3rd or 4th generation) at baseline or 6 months. We performed univariate, bivariate, and multivariable logistic regression and propensity-score weighted models to assess odds ratios (OR) and 95% confidence intervals (CI) for LTBI acquisition by birth sex among close contacts. Results: Of 1093, 504 (46%) female close contacts were IGRA positive compared to 295 of 745 (40%) men. The unadjusted OR for IGRA positivity among women vs men was 1.31 (95% CI: 1.08-1.58). Bivariate adjustments yielded ORs in women vs men ranging from 1.19 to 1.33 (P-value range:

Background: A major goal of tuberculosis (TB) epidemiological studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on the determinants of TB treatment outcomes is also important. Methods: We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period. Multivariable regression models adjusted for the study site were performed using second-generation p-values, a novel statistical approach. Associations with unfavorable treatment outcomes were tested for both RePORT-Brazil and SINAN cohorts. Findings: A total of 1,060 culture-confirmed TB patients were enrolled in RePORT-Brazil and 455,873 TB cases were reported to SINAN. Second-generation p-value analyses revealed that the cohorts were strikingly similar with regard to sex, age, use of antiretroviral therapy and positive initial smear sputum microscopy. However, diabetes, HIV infection, and smoking were more frequently documented in RePORT-Brazil. Illicit drug use, the presence of diabetes, and history of prior TB were associated with unfavorable TB treatment outcomes; illicit drug use was associated with such outcomes in both cohorts. Conclusions: There were important similarities in demographic characteristics and determinants of clinical outcomes between the RePORT-Brazil cohort and the Brazilian National registry of TB cases.

ABSTRACT The interferon gamma release assay (IGRA) has emerged as a useful tool for identifying latent tuberculosis infection (LTBI). This assay can be performed through testing platforms such as the QuantiFERON-TB Gold Plus (QFT-Plus) assay. This in vitro test has been incorporated into several guidelines worldwide and has recently been considered by the World Health Organization (WHO) for the diagnosis of LTBI. The possibility of systematically implementing IGRAs such as the QFT-Plus assay in centers that perform LTBI screening has been accelerated by the decreased availability of the tuberculin skin test (TST) in several countries. Nevertheless, the process to implement IGRA testing in routine clinical care has many gaps. The study utilized the expertise acquired by the laboratory teams of the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil consortium during study protocol implementation of LTBI screening of tuberculosis (TB) close contacts. RePORT-Brazil includes clinical research sites from Brazilian cities and is the largest multicenter cohort of TB close contacts in the country to date. Operational and logistical challenges faced during IGRA implementation in all study laboratories are described, as well as the solutions that were developed and led to the successful establishment of IGRA testing in RePORT-Brazil. The descriptions of the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with large TB burdens, such as Brazil. IMPORTANCE The IGRA has emerged as a useful tool for identifying persons with LTBI. Although the implementation of IGRAs is of utmost importance, to our knowledge there is scarce information on the identification of logistical and technical challenges for systematic screening for LTBI on a large scale. Thus, the descriptions of the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with large TB burdens, such as Brazil.

Some retrospective studies have found that HIV-infected women have a higher mortality risk than men after adjusting for baseline characteristics, while others have not. Anemia is a known predictor of HIV-related mortality. We assessed whether anemia contributed to the sex difference in mortality in our cohort.We conducted a retrospective cohort study among HIV-infected persons in care at the Comprehensive Care Center (Nashville, TN) between 1998 and 2009. Cox proportional hazards models compared time from first clinic visit to death and AIDS-defining events (ADE), adjusted for baseline characteristics with and without baseline hemoglobin.Of 3,633 persons, 879 (24%) were women. Women had lower median baseline hemoglobin compared to men: 12.4 g/dL (inter-quartile range (IQR) 11.3-13.4) vs. 14.4 (IQR 13.1-15.5), respectively (P

This article outlines the anatomic and physiologic basis for gastric conduit ischemia and the range of its possible manifestations, from superficial mucosal ischemia to gross conduit necrosis. Methods by which these complications are suspected and ultimately diagnosed are discussed, focusing on clinical and laboratory signs as the harbingers and the use of imaging and endoscopy for confirmation. From there, management options are detailed based on the Esophagectomy Complications Consensus Group classification of esophageal leak and gastric necrosis. Finally, the short- and long-term implications of these complications are reviewed., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Genetic polymorphisms have been associated with risk of antituberculosis treatment toxicity. We characterized associations with adverse events and treatment failure/recurrence among adults treated for tuberculosis in Brazil., Methods: Participants were followed in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil. We included persons with culture-confirmed drug-susceptible pulmonary tuberculosis who started treatment between 2015 and 2019, and who were eligible for pharmacogenetics. Treatment included 2 months of isoniazid, rifampin or rifabutin, pyrazinamide, and ethambutol, then 4 months of isoniazid and rifampin or rifabutin, with 24-month follow-up. Analyses included 43 polymorphisms in 20 genes related to antituberculosis drug hepatotoxicity or pharmacokinetics. Whole exome sequencing was done in a case-control toxicity subset., Results: Among 903 participants in multivariable genetic association analyses, NAT2 slow acetylator status was associated with increased risk of treatment-related grade 2 or greater adverse events, including hepatotoxicity. Treatment failure/recurrence was more likely among NAT2 rapid acetylators, but not statistically significant at the 5% level. A GSTM1 polymorphism (rs412543) was associated with increased risk of treatment-related adverse events, including hepatotoxicity. SLCO1B1 polymorphisms were associated with increased risk of treatment-related hepatoxicity and treatment failure/recurrence. Polymorphisms in NR1/2 were associated with decreased risk of adverse events and increased risk of failure/recurrence. In whole exome sequencing, hepatotoxicity was associated with a polymorphism in VTI1A, and the genes METTL17 and PRSS57, but none achieved genome-wide significance., Conclusion: In a clinical cohort representing three regions of Brazil, NAT2 acetylator status was associated with risk for treatment-related adverse events. Additional significant polymorphisms merit investigation in larger study populations, particularly regarding risk of treatment failure/recurrence., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mood disorders, including unipolar and bipolar depression, contribute significantly to the global burden of disease. Psychological therapy is considered a gold standard non-pharmacological treatment for managing these conditions; however, a growing body of evidence also supports the use of lifestyle therapies for these conditions. Despite some clinical guidelines endorsing the application of lifestyle therapies as a first-line treatment for individuals with mood disorders, there is limited evidence that this recommendation has been widely adopted into routine practice. A key obstacle is the insufficient evidence on whether lifestyle therapies match the clinical and cost effectiveness of psychological therapy, particularly for treating those with moderate to severe symptoms. The HARMON-E Trial seeks to address this gap by conducting a non-inferiority trial evaluating whether a multi-component lifestyle therapy program is non-inferior to psychological therapy on clinical and cost-effectiveness outcomes over 8-weeks for adults with major depressive disorder and bipolar affective disorder., Methods: This trial uses an individually randomised group treatment design with computer generated block randomisation (1:1). Three hundred and seventy-eight adults with clinical depression or bipolar affective disorder, a recent major depressive episode, and moderate-to-severe depressive symptoms are randomised to receive either lifestyle therapy or psychological therapy (adjunctive to any existing treatments, including pharmacotherapies). Both therapy programs are delivered remotely, via a secure online video conferencing platform. The programs comprise an individual session and six subsequent group-based sessions over 8-weeks. All program aspects (e.g. session duration, time of day, and communications between participants and facilitators) are matched except for the content and program facilitators. Lifestyle therapy is provided by a dietitian and exercise physiologist focusing on four pillars of lifestyle (diet, physical activity, sleep, and substance use), and the psychological therapy program is provided by two psychologists using a cognitive behavioural therapy approach. Data collection occurs at baseline, 8-weeks, 16-weeks, and 6 months with research assistants blinded to allocation. The primary outcome is depressive symptoms at 8 weeks, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) (minimal clinically important difference = 1.6). A pre-specified within-trial economic evaluation will also be conducted., Discussion: Should lifestyle therapy be found to be as clinically and cost effective as psychological therapy for managing mood disorders, this approach has potential to be considered as an adjunctive treatment for those with moderate to severe depressive symptoms., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12622001026718, registered 22nd July 2022., Protocol Version:  4.14, 26/06/2024., (© 2024. The Author(s).)

The impact of childhood abuse on the presentation of bipolar disorder could be further elucidated by comparing the networks of affective symptoms among individuals with and with no history of childhood abuse. Data from 476 participants in the Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study were used to fit several regularised Gaussian Graphical Models. Differences in the presentation of depressive and manic symptoms were uncovered: only among participants with a history of childhood abuse, inadequacy and pessimism were central symptoms in the network of depressive symptoms, while racing thoughts was an important symptom in the network of manic symptoms. Following network theory, focusing treatments at the symptom-level and on central symptoms - like inadequacy, pessimism, and racing thoughts - could be an effective approach for managing affective symptoms among the sizeable proportion of people with bipolar disorder who have experienced childhood abuse. This study contributes a thorough investigation of the networks of affective symptoms among participants with and with no history of childhood abuse, albeit limited by the use of a binary, self-report measure of childhood abuse, thereby emphasising the importance of assessing for childhood abuse and taking needed steps towards identifying novel targets for treating bipolar disorder., Competing Interests: Declaration of competing interest ALW has received grant/research support from Deakin University and the Rotary Club of Geelong. MT has received grant/research support from Deakin University. OMD has received grant/research support from the Brain and Behavior Foundation, Simons Autism Foundation, Stanley Medical Research Institute, Deakin University, Lilly, NHMRC, and Australasian Society for Bipolar and Depressive Disorders (ASBDD)/Servier. OMD has also received in kind support from BioMedica Nutracuticals, NutritionCare and Bioceuticals. MB has received grant/research support from MRFF, NHMRC, Congressionally Directed Medical Research Programs (CDMRP) USA, AEDRTC Australian Eating Disorders Research and Translation Centre, Patient-Centered Outcomes Research Institute (PCORI), Baszucki Brain Research Fund, Danmarks Frie Forskningsfond. Psykiatrisk Center Kobenhavn, Stanley Medical Research Institute, Victorian Government Department of Jobs, Precincts and Regions, Wellcome Trust, Victorian Medical Research Acceleration Fund, Controversias Psiquiatria Barcelona, CRE, Victorian COVID-19 Research Fund, Consultancies: Lundbeck, Sandoz, Servier, Medisquire, HealthEd, ANZJP, EPA, Janssen, Medplan, RANZCP, Abbott India, ASCP, International Society of Bipolar Disorder, Precision Psychiatry, Penn State College of Medicine, Shanghai Mental Health Centre in the past 3 years – all unrelated to this work. LGS has received grant/research support from PCORI, NIH, HRSA, Tiny Blue Dot Foundation, and AFSP. She has also received support as a member of the Miliken Institute's Scientific Advisory Board as well as royalties form New Harbinger for her two, published books on bipolar disorder. MT was an employee of Lilly (1997 to 2008) and has received honoraria from or consulted for Abbott, Abbvie, AstraZeneca, Alkermes, Atai, Biohaven Pharmaceuticals, Squibb, Rapport Neurosciences, Lilly, Johnson & Johnson, Otsuka, Merck, Sunovion, Intra-Cellular Therapies, NeuroRX, Roche, Elan, Lundbeck, Teva, Minerva, Neurocrine Biosciences, NoemaPharma, Pfizer; his spouse was a full time employee at Lilly (1998–2013). MGM has received grant/research support from Janseen Pharmaceuticals. RCS has received grant/research support from the National Institutes of Mental Health, the Patient Centered Outcomes Research Institute, AbbVie Inc, Alto Pharmaceuticals, Boehringer Ingelheim, Denovo Biopharma, Gate Neuroscience, InMune Bio, Intra-cellular Therapies, Johnson & Johnson Innovative Medicine, LivaNova PLC, Navitor Pharmaceuticals, Neumora, Neurocrine Biosciences, Neurorx, Novartis AG, Otsuka Pharmaceuticals, Sumitomo Pharma America, and Supernus Pharmaceuticals. RCS has also consulted for Boehringer Ingelheim, Denovo Biopharma, Equulus Therapeutics, Evecxia Therapeutics LLC, Johnson & Johnson Innovative Medicine, Neurorx, Novartis AG, Otsuka Pharmaceuticals, Seelos Therapeutics, Inc., Sumitomo Pharma America, and Supernus Pharmaceuticals and has received royalties from Springer-Nature Group and Wolters-Kluwer NV. MJO has received grant/research support from Otsuka and is a consultant to Neurocrine, Inc., both unrelated to this work. In the last 10 years, DVI has served as a consultant for Alkermes, Allergan, Angelini, Autobahn, Axsome, Biogen, Boehringer Ingelheim, the Centers for Psychiatric Excellence, Clexio, Delix, Jazz, Lundbeck, Neumora, Otsuka, Precision Neuroscience, Relmada, Sage Therapeutics, and Sunovion. He has received grant/research support (paid to his institutions) from Alkermes, AstraZeneca, Brainsway, LiteCure, NeoSync, Otsuka, Roche, and Shire. SLM has been a consultant to or member of the scientific advisory boards of Axsome, Idorsia, Kallyope, Levo, Neurocrine, Novo Nordisk, Otsuka, Sunovion, and Takeda. She has been a principal or co-investigator on studies sponsored by Neurocrine, Novo Nordisk, Otsuka, and Sunovion. She is also an inventor on United States Patent No 6323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patent's assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent. AT has received travel/grant support from NHMRC, AMP Foundation, Stroke Foundation, Hunter Medical Research Institute, Helen Macpherson Smith Trust, Schizophrenia Fellowship NSW, SMHR, ISAD, the University of Newcastle, and Deakin University. AAN is a consultant for Alkermes, Clexio, Ginger/Headspace Health, Janssen, Merck, Neuronetics, NeuroRx, Otsuka, Protagenics, SAGE, Sunovion, Unravel Bioscience, received honoraria from Belvior, EISAI, Psychiatric Annals Slack Publications, Wiley Depression and Anxiety, received royalties from Guilford Publications, Up-to-Date Wolters Kluwer Health, has been a scientific advisory board member for Altimate, Flow, Milken Center for Strategic Philanthropy, Myriad, and adjudication committee member for Novartis., (Copyright © 2024. Published by Elsevier B.V.)

Background: Therapeutic drug ranges (TDR) for standard anti-tuberculosis (TB) treatment have been determined based on expected drug levels at least 2 hours after taking the dose. In this study we constructed TDR for TB drug levels based on minimizing drug toxicity and maximizing treatment effectiveness., Methods: Participants were followed prospectively in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil observational cohort study. We focused on participants with culture-confirmed drug-susceptible pulmonary TB who underwent standard TB therapy. TDR were estimated for each TB drug separately: isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA). TDR were defined as drug concentrations that were both safe and effective: safety was defined as the probability of having an ADR of at most 5%, while effectiveness was defined as a probability of at least 95% of not having either TB treatment failure or recurrence., Results: There were 765 plasma samples from 448 patients; 110 (24.6%) were people with HIV, 9 (2.0%) had a grade 3 or higher ADR, and 15 (3.3%) had treatment failure/recurrence. Higher drug concentrations of INH, RIF and EMB were associated with increased odds of having ADR. High concentrations of INH suggested protection against treatment failure/recurrence. Estimated therapeutic drug range for INH (2.3-8.2 µg/ml) and for RIF (0.5-7.5 µg/ml) differed from the currently recommended drug ranges (3-5 µg/ml and 8-24 µg/ml, respectively). Estimates for PZA and EMB were similar to the currently recommended values., Conclusions: Our estimated upper end TDR were higher for INH and lower for RIF compared to currently recommended ranges.

Background: We conducted the first non-inferiority, randomised controlled trial to determine whether lifestyle therapy is non-inferior to psychotherapy with respect to mental health outcomes and costs when delivered via online videoconferencing., Methods: An individually randomised, group treatment design with computer-generated block randomisation was used. Between May 2021-April 2022, 182 adults with a Distress Questionnaire-5 score = ≥8 (indicative depression) were recruited from a tertiary mental health service in regional Victoria, Australia and surrounds. Participants were assigned to six 90-min sessions over 8-weeks using group-based, online videoconferencing comprising: (1) lifestyle therapy (targeting nutrition, physical activity) with a dietitian and exercise physiologist (n = 91) or (2) psychotherapy (Cognitive Behavioural Therapy) with psychologists (n = 91). The primary outcome was Patient Health Questionnaire-9 (PHQ-9) depression at 8-weeks (non-inferiority margin ≤2) using Generalised Estimating Equations (GEE). Cost-minimisation analysis estimated the mean difference in total costs from health sector and societal perspectives. Outcomes were assessed by blinded research assistants using Computer Assisted Telephone Interviews. Results are presented per-protocol (PP) and Intention to Treat (ITT) using beta coefficients with 95% Confidence Intervals (CIs)., Findings: The sample was 80% women (mean: 45-years [SD:13.4], mean PHQ-9:10.5 [SD:5.7]. An average 4.2 of 6 sessions were completed, with complete data for n = 132. Over 8-weeks, depression reduced in both arms (PP: Lifestyle (n = 70) mean difference:-3.97, 95% CIs:-5.10, -2.84; and Psychotherapy (n = 62): mean difference:-3.74, 95% CIs:-5.12, -2.37; ITT: Lifestyle (n = 91) mean difference:-4.42, 95% CIs: -4.59, -4.25; Psychotherapy (n = 91) mean difference:-3.82, 95% CIs:-4.05, -3.69) with evidence of non-inferiority (PP GEE β:-0.59; 95% CIs:-1.87, 0.70, n = 132; ITT GEE β:-0.49, 95% CIs:-1.73, 0.75, n = 182). Three serious adverse events were recorded. While lifestyle therapy was delivered at lower cost, there were no differences in total costs (health sector adjusted mean difference: PP AUD$156 [95% CIs -$182, $611, ITT AUD$190 [95% CIs -$155, $651] ]; societal adjusted mean difference: PP AUD$350 [95% CIs:-$222, $1152] ITT AUD$ 408 [95% CIs -$139, $1157]., Interpretation: Remote-delivered lifestyle therapy was non-inferior to psychotherapy with respect to clinical and cost outcomes. If replicated in a fully powered RCT, this approach could increase access to allied health professionals who, with adequate training and guidelines, can deliver mental healthcare at comparable cost to psychologists., Funding: This trial was funded by the Australian Medical Research Future Fund (GA133346) under its Covid-19 Mental Health Research Grant Scheme., Competing Interests: This trial was funded by the National Health and Medical Research Council’s (NHMRC) Medical Research Future Fund–COVID-19 Mental Health Research Australian Government Department of Health (GA133346). AO is supported by a NHMRC Emerging Leader 2 Fellowship (2009295). FNJ is supported by an NHMRC Investigator Grant (#1194982). FNJ has received fellowship funding support from the National Health and Medical Research Council (#1194982) and payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Malaysian Society of Gastroenterology and Hepatology, JNPN Congress, American Nutrition Association, Personalised Nutrition Summit, and American Academy of Craniofacial Pain, is a Scientific Advisory Board member of Dauten Family Centre for Bipolar Treatment Innovation (unpaid) and Zoe Nutrition (unpaid), has written two books for commercial publication on the topic of nutritional psychiatry and gut health, and is the principal investigator for the MicroFit Study. She is Director of the Food & Mood Centre, Deakin University, which has received research funding support from Be Fit Food, Bega Dairy and Drinks, and the a2 Milk Company and philanthropic research funding support from the Waterloo Foundation, Wilson Foundation, the JTM Foundation, the Serp Hills Foundation, the Roberts Family Foundation, and the Fernwood Foundation. SR is supported by an NHMRC Investigator Grant (2017506). MB is supported by a NHMRC Senior Principal Research Fellowship and Leadership 3 Investigator grant (1156072 and 2017131). MTey is supported by a NHMRC Emerging Leadership Fellowship (APP1195335). JS is supported by core funding to the Australian Centre for Behavioural Research in Diabetes provided by the collaboration between Diabetes Victoria and Deakin University. VV is supported by the Rural Health Multidisciplinary Training program. SMah has received funding from Education in Nutrition to provide a professional development presentation and Red Island Olive Oil for social media promotion. MMor has received research grants related to antimicrobial stewardship, discharge medication, consulting fees from Primary Health Networks of Gold Coast and Western Australia related to Primary Sense software. Australian Health Policy Collaboration, RACGP, Australian Department of Health and Aged Care (DoHAC), conference support from RACGP various as chair of Expert Committee for Quality Care, participation in DSMBs for Primary Sense and DoHAC and is a member of Arthritis Australia and Bond University Boards. The contents of the published material are solely the responsibility of the individual authors and do not reflect the views of the funding bodies. The authors have no interests to declare., (© 2024 The Authors.)

Objective: We sought to determine the association of hormonal contraception (HC) and cardiometabolic outcomes among women with human immunodeficiency virus (HIV). Methods: We included women with HIV aged 18-45 years in clinical care in the Southeastern United States between 1998 and 2018. Oral and injectable HC use was captured from medication records. Our outcomes included incident cardiovascular/thrombotic disease (CVD) (atherosclerosis, hypertension, cerebrovascular disease, thrombosis, and heart failure) and incident metabolic disorders (diabetes, dyslipidemia, obesity, and non-alcoholic steatohepatitis). We excluded women with prevalent conditions. We used multivariable marginal structural models to examine time-varying current and cumulative HC use and cardiometabolic outcomes in separate analyses, adjusting for age, race, smoking, time-varying comorbidities, CD4 cell count, HIV RNA, and antiretroviral use. Women with HC exposure were compared with women without HC exposure. Results: Among the 710 women included, 201 women (28%) used HC. CVD analyses included 603 women without prevalent CVD and 93 incident events; metabolic analyses included 365 women without prevalent metabolic disease and 150 incident events. Current and cumulative oral HC use was associated with increased odds of CVD, though this was not statistically significant (adjusted odds ratio [aOR] = 2.08, [95% confidence interval (CI): 0.80-5.43] and aOR = 1.24 [95% CI: 0.96-1.60] per year of use, respectively). Oral HC was not associated with risk of incident metabolic disorders. Depot medroxyprogesterone acetate (DMPA) was not associated with risk of incident CVD. Current and cumulative DMPA use was significantly associated with decreased odds of incident metabolic disorders (aOR = 0.48 [95% CI: 0.23, 1.00] and aOR = 0.65 [95% CI: 0.42-1.00] per year of use, respectively). Conclusion: Our results suggest that cardiovascular risk should be considered when selecting contraception for women with HIV.

Human Immunodeficiency Virus (HIV)-positive individuals lost to follow-up from particular clinics may not be lost to care (LTC). After linking Vanderbilt's Comprehensive Care Clinic cohort to Tennessee's statewide HIV surveillance database, LTC decreased from 48.4% to 35.0% at 10 years. Routine surveillance linkage by domestic HIV clinics would improve LTC and retention measure accuracy., Competing Interests: Potential conflicts of interest. P. F. R. received honoraria from Gilead & Janssen Pharmaceuticals in 2021. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this observational study, we assessed the extent to which a community-created pilot intervention, providing trauma-informed care for persons with HIV (PWH), affected HIV care retention and viral suppression among PWH attending an HIV Services Organization in the Southern US. PWH with trauma exposure and/or trauma symptoms (N = 166) were offered a screening and referral to treatment (SBIRT) session. Per self-selection, 30 opted-out, 29 received SBIRT-Only, 25 received SBIRT-only but reported receiving other behavioral health care elsewhere, and 82 participated in the Safety and Stabilization (S&S) Intervention. Estimates from multivariable logistic regression analyses indicated S&S Intervention participants had increased retention in HIV care (adjusted odds ratio [aOR] 5.46, 95% CI 1.70-17.50) and viral suppression (aOR 17.74, 95% CI 1.83-172), compared to opt-out participants. Some evidence suggested that PTSD symptoms decreased for intervention participants. A randomized controlled trial is needed to confirm findings., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Critical Path Institute convened the Support Flexible Approaches to PRO Data Collection project as part of the eCOA: Getting Better Together Initiative which was instigated to identify and address common challenges and drive positive change with eCOA implementation in clinical trials. The project aimed to identify clinical trial stakeholders' concerns related to electronic PRO (ePRO) implementation and propose areas of improvement via simplification and flexibility . One workstream focused on patient-/site-centric approaches for simplification and surveyed representatives of clinical sites and site monitors for their perspectives. A semi-structured questionnaire was developed and distributed via snowball sampling to site professionals and clinical research associates (CRAs) that had ePRO experience who had been identified via representative groups or sponsor-led site networks. Responses were received from various site roles across a range of global regions; the largest contribution was from the United States. Topics raised included helpdesk capabilities, technical concerns, device types, and user interfaces among others and are discussed further in this paper. The feedback derived from the questionnaire provided the basis for concrete ideas that sponsors should consider incorporating into protocol design for participant visits, technology use, devices, and methods of back-up data collection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Populations with common physical diseases - such as cardiovascular diseases, cancer and neurodegenerative disorders - experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associated with worse outcomes, reduced adherence to treatment, increased mortality, and greater health care utilization and costs. Comorbidity can also result in a range of clinical challenges, such as a more complicated therapeutic alliance, issues pertaining to adaptive health behaviors, drug-drug interactions and adverse events induced by medications used for physical and mental disorders. Potential explanations for the high prevalence of the above comorbidity involve shared genetic and biological pathways. These latter include inflammation, the gut microbiome, mitochondrial function and energy metabolism, hypothalamic-pituitary-adrenal axis dysregulation, and brain structure and function. Furthermore, MDD and physical diseases have in common several antecedents related to social factors (e.g., socioeconomic status), lifestyle variables (e.g., physical activity, diet, sleep), and stressful live events (e.g., childhood trauma). Pharmacotherapies and psychotherapies are effective treatments for comorbid MDD, and the introduction of lifestyle interventions as well as collaborative care models and digital technologies provide promising strategies for improving management. This paper aims to provide a detailed overview of the epidemiology of the comorbidity of MDD and specific physical diseases, including prevalence and bidirectional risk; of shared biological pathways potentially implicated in the pathogenesis of MDD and common physical diseases; of socio-environmental factors that serve as both shared risk and protective factors; and of management of MDD and physical diseases, including prevention and treatment. We conclude with future directions and emerging research related to optimal care of people with comorbid MDD and physical diseases., (© 2023 World Psychiatric Association.)

Background: Local anaesthetic thoracoscopy (LAT) can be a vital procedure for diagnosis of unexplained pleural effusions. Traditionally, poudrage for pleurodesis and insertion of a large bore drain necessitated admission. There has been a shift towards performing LAT as a day case procedure with indwelling pleural catheter (IPC) insertion. This was advocated during the COVID pandemic by the British Thoracic Society (BTS). To determine the feasibility of such pathways, continuous evaluations are required., Methods: All day case LAT procedures with IPC insertion, performed in theatre, were identified at two large district general hospitals (Northumbria HealthCare in the North East of England and Victoria Hospital, NHS Fife, in Scotland). Rapid pleurodesis with talc was not performed due to local staffing problems. All patients had their LAT in theatre under conscious sedation with a rigid scope. Demographics, clinical, radiological and histopathological characteristics and outcomes were collected., Results: 79 patients underwent day case LAT. The lung did not deflate, meaning biopsies were not enabled, in four of the patients. The mean age was 72 years (standard deviation 13). Fifty-five patients were male and twenty-four were female. The main diagnoses were lung cancers, mesotheliomas and fibrinous pleuritis with an overall diagnostic sensitivity of 93%. Other diagnoses were breast, tonsillar, unknown primary cancers and lymphomas. Seventy-three IPCs were simultaneously placed and, due to normal macroscopic appearances in two patients, two large bore drains were placed and removed within one hour of LAT termination. Sixty-six (88%) patients were discharged on the same day. Seven patients required admission: one for treatment of surgical emphysema, four because they lived alone, one for pain control and one for control of a cardiac arrythmia. Within 30 days, there were five IPC site infections with two resultant empyemas (9%), with no associated mortality. Two patients developed pneumonia requiring admission and one patient required admission for pain management. The median number of days for which the IPCs remained in situ was 78.5 days (IQR 95). The median length of stay (LoS) was 0 days (IQR 0). No patients required further interventions for pleural fluid management., Conclusions: Day case LAT with IPC insertion is feasible with this current set up, with a median stay of 0 days, and should be widely adopted. The health economics of preventing admission are considerable, as our previous analysis showed a median length of stay of 3.96 days, although we are not comparing matched cohorts.

Background: Successful tuberculosis (TB) treatment is necessary for disease control. The World Health Organization (WHO) has a target TB treatment success rate of ≥90%. We assessed whether the different types of unfavorable TB treatment outcome had different predictors., Methods: Using data from Regional Prospective Observational Research for Tuberculosis-Brazil, we evaluated biological and behavioral factors associated with each component of unsuccessful TB outcomes, recently updated by WHO (death, loss to follow-up [LTFU], and treatment failure). We included culture-confirmed, drug-susceptible, pulmonary TB participants receiving standard treatment in 2015-2019. Multinomial logistic regression models with inverse probability weighting were used to evaluate the distinct determinants of each unsuccessful outcome., Results: Of 915 participants included, 727 (79%) were successfully treated, 118 (13%) were LTFU, 44 (5%) had treatment failure, and 26 (3%) died. LTFU was associated with current drug-use (adjusted odds ratio [aOR] = 5.3; 95% confidence interval [CI], 3.0-9.4), current tobacco use (aOR = 2.9; 95% CI, 1.7-4.9), and being a person with HIV (PWH) (aOR = 2.0; 95% CI, 1.1-3.5). Treatment failure was associated with PWH (aOR = 2.7; 95% CI, 1.2-6.2) and having diabetes (aOR = 2.2; 95% CI, 1.1-4.4). Death was associated with anemia (aOR = 5.3; 95% CI, 1.4-19.7), diabetes (aOR = 3.1; 95% CI, 1.4-6.7), and PWH (aOR = 3.9; 95% CI, 1.3-11.4). Direct observed therapy was protective for treatment failure (aOR = 0.5; 95% CI, .3-.9) and death (aOR = 0.5; 95% CI, .2-1.0)., Conclusions: The treatment success rate was below the WHO target. Behavioral factors were most associated with LTFU, whereas clinical comorbidities were correlated with treatment failure and death. Because determinants of unsuccessful outcomes are distinct, different intervention strategies may be needed to improve TB outcomes., Competing Interests: Potential conflicts of interest. The authors do not have an association that might pose a conflict of interest. V. C. R. reports grants or contracts outside of the submitted work from TB Alliance for Drug Development (NC-008), Impacto da COVID-19 Nas Manifestações Clínicas, Diagnóstico, Desfecho Do Tratamento e Resposta Imune para Tuberculose Pulmonar (440933/2020-0 to CNPq account (not to self), Associative BRICS Research in COVID-19 and Tuberculosis (ABRICOT) (G-202105-67821 to Fiotec), RePORT International Data Harmonization (R-202108-68053 to Fiotec), Transcriptional Signature of TB in advanced HIV (DAA3-18-64313 to Fiotec), Predictors of Resistance Emergence Evaluation in Multidrug-resistant Tuberculosis patients on Treatment – PREEMPT (R01AI134430), Caribbean, Central, and South America network for HIV Epidemiology (CCASAnet) (U01AI069923 to Fiotec), and immunogenetic predictors of active and incipient TB in HIV-negative and -positive close TB contacts (R01AI147765 to Fiotec); consulting fees paid to self from ONU-OMS Country review for HIV response Myanmar; payment or honoraria paid to self from GLAXOSMITHKLINE BRASIL LTDA, Qiagen (Infecto Rio Conference), and virology education (Infecto Rio Conference); payment directly to the conference for registration for ViiV 18 European AIDS conference; and payment directly to self from NIH Data Safety Monitoring Board., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To explore symptoms and disease impacts of Crohn's disease and to develop a new patient-reported outcomes (PRO) measure according to industry best practices., Methods: A conceptual model of relevant symptoms experienced by patients with Crohn's disease was developed following a literature review. Three rounds of combined qualitative semi-structured concept elicitation and cognitive debriefing interviews with 36 patients (≥ 16 years) with Crohn's disease and 4 clinicians were conducted to further explore the most commonly reported and most bothersome symptoms to patients. Interview results were used to update the conceptual model as well as items and response options included in The Crohn's Disease Diary, a new PRO measure., Results: All patients (N = 36) reported abdominal pain, loose or liquid bowel movements, and high or increased frequency of bowel movements, with most reporting these symptoms spontaneously (100%, 92%, and 75%, respectively). All patients reported bowel movement urgency, but 61% reported this symptom only when probed. Most also reported that symptoms impacted activities of daily living, work/school, and emotional, social, and physical functioning (overall, 78%-100%; spontaneously, 79% - 92%). Data regarding core symptoms of Crohn's disease from clinician concept elicitation interviews supported patient data. The 17-item Crohn's Disease Diary assesses core symptoms and impacts of Crohn's disease over 24 h, and extraintestinal manifestations over 7 days. The content validity of the diary was confirmed during cognitive debriefing interviews., Conclusion: The Crohn's Disease Diary is a new PRO measure for the assessment of Crohn's disease symptoms and impacts, developed according to industry best practices., (© 2022. The Author(s).)

Background: Since the availability of antiretroviral therapy, mortality rates among people with HIV (PWH) have decreased; however, this does not quantify premature deaths among PWH, and disparities persist., Methods: We examined all-cause and premature mortality among PWH receiving care at the Vanderbilt Comprehensive Care Clinic from January 1998 to December 2018. Mortality rates were compared by demographic and clinical factors, and adjusted incidence rate ratios (aIRRs) were calculated using multivariable Poisson regression. For individuals who died, age-adjusted years of potential life lost (aYPLL) per total person-years living with HIV were calculated from US sex-specific life tables, and sex and race differences were examined using multivariable linear regression., Results: Among 6531 individuals (51% non-Hispanic [NH] White race, 40% NH Black race, 21% cis-gender women, 78% cis-gender men) included, 956 (14.6%) died. In adjusted analysis, PWH alive in the most recent calendar era (2014-2018) had decreased risk of mortality compared with those in the earliest calendar era (1998-2003; aIRR, 0.22; 95% CI, 0.17-0.29), and women had increased risk of death compared with men (aIRR, 1.31; 95% CI, 1.12-1.54). Of those who died, Black women had the highest aYPLL (aIRR, 592.5; 95% CI, 588.4-596.6), followed by Black men (aIRR, 470.7; 95% CI, 468.4-472.9), White women (aIRR, 411.5; 95% CI, 405.6-417.4), then White men (aIRR, 308.6; 95% CI, 308.0-309.2). In adjusted models, higher YPLL remained associated with NH Black race and cis-gender women, regardless of HIV risk factor., Conclusions: Despite marked improvement over time, sex disparities in mortality as well as sex and race disparities in YPLL remained among PWH in this cohort., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Approximately 1.1 million people living with HIV live in the United States, and the incidence is highest in Southeastern United States. Electronic patient portal prevalence is increasing and can improve engagement in primary medical care. Retention in care and viral suppression-measures of engagement in HIV care-are associated with decreased HIV transmission, morbidity, and mortality., Objective: We aimed to determine if patient portal access among people living with HIV was associated with retention and viral suppression., Methods: We conducted an observational cohort study among people living with HIV in care at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee) from 2011-2016. Individual access was defined as patient portal account registration at any point in the year prior. Retention was defined as ≥2 kept appointments or HIV lab measurements ≥3 months apart within a 12-month period. Viral suppression was defined as the last viral load in the calendar year <200 copies/mL. We calculated adjusted prevalence ratios (aPRs) and 95% CIs using modified Poisson regression with generalized estimating equations to estimate the association of portal access with retention and viral suppression., Results: We included 4237 people living with HIV contributing 16,951 person-years of follow-up (median 5, IQR 3-5 person-years). The median age was 43 (IQR 33-50) years. Of the 4237 people living with HIV, 78.1% (n=4237) were male, 40.8% (n=1727) were Black non-Hispanic, and 56.5% (n=2395) had access. Access was independently associated with retention (aPR 1.13, 95% CI 1.10-1.17) and viral suppression (aPR 1.18, 95% CI 1.14-1.22)., Conclusions: In this population, patient portal access was associated with retention and viral suppression. Future prospective studies should assess the impact of increasing portal access among people living with HIV on these HIV outcomes., (©Cassandra Oliver Schember, Sarah E Scott, Cathy A Jenkins, Peter F Rebeiro, Megan Turner, Sally S Furukawa, Carmen Bofill, Zhou Yan, Gretchen P Jackson, April C Pettit. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 25.07.2022.)

Background: There is increasing recognition of the substantial burden of mental health disorders at an individual and population level, including consequent demand on mental health services. Lifestyle-based mental healthcare offers an additional approach to existing services with potential to help alleviate system burden. Despite the latest Royal Australian New Zealand College of Psychiatrists guidelines recommending that lifestyle is a 'first-line', 'non-negotiable' treatment for mood disorders, few such programs exist within clinical practice. Additionally, there are limited data to determine whether lifestyle approaches are equivalent to established treatments. Using an individually randomised group treatment design, we aim to address this gap by evaluating an integrated lifestyle program (CALM) compared to an established therapy (psychotherapy), both delivered via telehealth. It is hypothesised that the CALM program will not be inferior to psychotherapy with respect to depressive symptoms at 8 weeks., Methods: The study is being conducted in partnership with Barwon Health's Mental Health, Drugs & Alcohol Service (Geelong, Victoria), from which 184 participants from its service and surrounding regions are being recruited. Eligible participants with elevated psychological distress are being randomised to CALM or psychotherapy. Each takes a trans-diagnostic approach, and comprises four weekly (weeks 1-4) and two fortnightly (weeks 6 and 8) 90-min, group-based sessions delivered via Zoom (digital video conferencing platform). CALM focuses on enhancing knowledge, behavioural skills and support for improving dietary and physical activity behaviours, delivered by an Accredited Exercise Physiologist and Accredited Practising Dietitian. Psychotherapy uses cognitive behavioural therapy (CBT) delivered by a Psychologist or Clinical Psychologist, and Provisional Psychologist. Data collection occurs at baseline and 8 weeks. The primary outcome is depressive symptoms (assessed via the Patient Health Questionnaire-9) at 8 weeks. Societal and healthcare costs will be estimated to determine the cost-effectiveness of the CALM program. A process evaluation will determine its reach, adoption, implementation and maintenance., Discussion: If the CALM program is non-inferior to psychotherapy, this study will provide the first evidence to support lifestyle-based mental healthcare as an additional care model to support individuals experiencing psychological distress., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12621000387820 , Registered 8 April 2021., (© 2022. The Author(s).)

Background: Women with human immunodeficiency virus (WWH) have low rates of hormonal or long-acting contraceptive use. Few studies have described contraception use among WWH over time., Methods: We examined contraception (including all forms of hormonal contraception, intrauterine devices, and bilateral tubal ligations) use among cisgender women aged 18-45 years in care at Vanderbilt's human immunodeficiency virus (HIV) clinic in Nashville, Tennessee, from 1998 through 2018. Weighted annual prevalence estimates of contraception use were described. Cox proportional hazards models examined factors associated with incident contraception use and pregnancy., Results: Of the 737 women included, median age at clinic entry was 31 years; average follow-up was 4.1 years. At clinic entry, 47 (6%) women were on contraception and 164 (22%) were pregnant. The median annual percentage of time on any contraception use among nonpregnant women was 31.7% and remained stable throughout the study period. Younger age was associated with increased risk of pregnancy and contraceptive use. Psychiatric comorbidity decreased likelihood of contraception (adjusted hazard ratio [aHR], 0.52 [95% CI {confidence interval}, .29-.93]) and increased likelihood of pregnancy (aHR, 1.77 [95% CI, .97-3.25]). While not associated with contraceptive use, more recent year of clinic entry was associated with higher pregnancy risk. Race, substance use, CD4 cell count, HIV RNA, smoking, and antiretroviral therapy were not associated with contraception use nor pregnancy., Conclusions: Most WWH did not use contraception at baseline nor during follow-up. Likelihood of pregnancy increased with recent clinic entry while contraception use remained stable over time. Continued efforts to ensure access to effective contraception options are needed in HIV clinics., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Unwanted weight gain affects some people living with human immunodeficiency virus (HIV) who are prescribed integrase strand transfer inhibitors (INSTIs). Mechanisms and risk factors are incompletely understood., Methods: We utilized 2 cohorts to study pharmacogenetics of weight gain following switch from efavirenz- to INSTI-based regimens. In an observational cohort, we studied weight gain at 48 weeks following switch from efavirenz- to INSTI-based regimens among patients who had been virologically suppressed for at least 2 years at a clinic in the United States. Associations were characterized with CYP2B6 and UGT1A1 genotypes that affect efavirenz and INSTI metabolism, respectively. In a clinical trials cohort, we studied weight gain at 48 weeks among treatment-naive participants who were randomized to receive efavirenz-containing regimens in AIDS Clinical Trials Group studies A5095, A5142, and A5202 and did not receive INSTIs., Results: In the observational cohort (n = 61), CYP2B6 slow metabolizers had greater weight gain after switch (P = .01). This was seen following switch to elvitegravir or raltegravir, but not dolutegravir. UGT1A1 genotype was not associated with weight gain. In the clinical trials cohort (n = 462), CYP2B6 slow metabolizers had lesser weight gain at week 48 among participants receiving efavirenz with tenofovir disoproxil fumarate (P = .001), but not those receiving efavirenz with abacavir (P = .65). Findings were consistent when stratified by race/ethnicity and by sex., Conclusions: Among patients who switched from efavirenz- to INSTI-based therapy, CYP2B6 genotype was associated with weight gain, possibly reflecting withdrawal of the inhibitory effect of higher efavirenz concentrations on weight gain. The difference by concomitant nucleoside analogue is unexplained., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to determine whether adjuvant chemotherapy (AC) provides a survival benefit in patients with nonmetastatic poorly differentiated colorectal neuroendocrine carcinomas (CRNECs) following resection., Background: There is little evidence to support the association between use of AC and improved overall survival (OS) in patients with CRNECs., Methods: Patients with resected non-metastatic CRNECs were identified in the National Cancer Database (2004-2014). Inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare OS of patients in different treatment groups., Results: A total of 806 patients diagnosed between 2004 and 2014 met the study entry criteria. Of these, 394 patients (48.9%) received AC. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC versus observation [57.4 (interquartile range, IQR, 14.8-153.8) vs 38.2 (IQR, 10.4-125.4) months; P = 0.007]. In IPTW-adjusted Cox proportional hazards regression analysis, AC was associated with a significant OS benefit [hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.64-0.84; P < 0.001]. The results were consistent across subgroups stratified by pathologic T stage, pathologic N stage, and surgical margin status. Subgroup analysis according to tumor location demonstrated improved OS in the adjuvant therapy cohort among patients with left-sided neuroendocrine carcinomas (HR, 0.55; 95% CI, 0.44-0.68), but not in those with right-sided disease (HR, 0.89; 95% CI, 0.74-1.07)., Conclusions: Patients with nonmetastatic CRNECs may derive survival benefit from AC. These findings support current guidelines recommending AC in patients with poorly differentiated neuroendocrine carcinomas in the colon and rectum. Efforts in education and adherence to national guidelines for NECs are needed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People living with HIV (PLWH) experience high rates of mood disorders (major depression and bipolar affective disorder) which in the general population have been associated with noncommunicable disease (NCD) risk. We examined whether prevalent mood disorders are associated with incident NCDs and multimorbidity (accumulation of ≥2 NCDs) in PLWH., Setting: Adult HIV clinic cohort in Nashville, Tennessee, between 1998 and 2015., Methods: PLWH with ≥1 year of follow-up in the clinic were assessed for cardiovascular disease, metabolic syndrome (any 3 of hypertension, hyperlipidemia, diabetes, or obesity), chronic kidney and liver disease, non-AIDS-defining cancers, and dementia. Only mood disorders documented during the first year of care were included. Cumulative incidence and adjusted subhazard ratios (aSHRs) were calculated for risk of NCDs and multimorbidity with death as a competing risk. Multivariable Cox models estimated mortality risk after multimorbidity., Results: Of 4140 adults, 24% had a mood disorder diagnosed in the first year of care, 51% had ≥1 NCD at baseline, and there were 2588 incident NCDs during the study period. Mood disorders were associated with increased risk of first NCD (aSHR = 1.29, 95% confidence interval: 1.06 to 1.57), incident multimorbidity (aSHR ranging from 1.04 to 1.42), and metabolic syndrome (aSHR = 1.29, 95% confidence interval: 1.02 to 1.64). Mood disorders were not conclusively associated with mortality risk after multimorbidity., Conclusions: PLWH with mood disorders were at increased risk of incident NCDs and multimorbidity, particularly metabolic syndrome. Focused prevention and treatment of NCDs may reduce the burden of multimorbidity in this high-risk group.

Cannabis use is prevalent among HIV-positive persons, but evidence regarding the impact of cannabis in HIV-positive persons is limited. We conducted a retrospective cohort study of HIV-positive adults initiating their first antiretroviral therapy (ART) regimen. A dedicated intake form assessed self-reported cannabis use in the preceding 7 days at each visit. The relationships between time-varying cannabis use and body mass index (BMI), CD4+ T-cell count, and HIV-1 RNA levels were assessed using random effects models adjusted for age, sex, race, and other reported substance use. 4290 patient-visits from 2008 to 2011 were available from 1010 patients. Overall, there were no statistically significant differences in CD4+ T-cell count and BMI across multiple adjusted models using different measures of cannabis use (ever use during the study period, any use, and number of times used in the preceding 7 days). Cannabis use by all three measures was associated with greater odds of having a detectable viral load at a given visit than no reported use (OR 2.02, 1.72, and 1.08, respectively; all adjusted p < 0.05). Self-reported cannabis use was not associated with changes in BMI or CD4+ T-cell count in ART-naïve HIV-positive persons starting treatment. However, reported cannabis use by multiple categories was associated with having a detectable HIV-1 RNA during the study period. Associations between cannabis use, adherence, and HIV-related outcomes merit further study.

Background: Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)-based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens., Methods: Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)-, and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals., Results: Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/μL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant., Conclusions: Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

HIV and hepatitis C virus (HCV) coinfection is associated with poor health outcomes. This study was designed to assess risk factors for and mortality with coinfection before direct-acting antiviral treatment availability in a state with an evolving opioid epidemic. HCV infection was determined from review of the medical record at two clinics serving the majority of people living with HIV (PLWH) in care in Middle Tennessee from 2004 to 2013. Association of potential risk factors with HCV-positivity was assessed using logistic regression. Association of HCV-positivity with mortality was assessed with a Cox proportional hazards model, adjusting for selected covariates. A total of 3,501 patients were included: 24% female; 51% men who have sex with men; 47% white; 44% African American/black; median age of 38 at their first visit; median most recent CD4 count 502 cells/μL (301-716); and HIV viral load 47 copies/mL (39-605); followed for a median of 3.0 (1-5) years. Prevalence of HCV was 13%. Those with a history of injection drug use (IDU) demonstrated the highest odds of HCV-positivity [odds ratio 12.94; 95% confidence interval (CI) 9.39-17.83]. There were 305 deaths; median age at death was 47 years (40-53). HCV coinfection was associated with greater mortality (hazard ratio 1.61; 95% CI 1.20-2.17; p  < .001). Among PLWH, HCV coinfection was associated with IDU and an independent predictor of mortality. These results affirm the importance of HCV coinfection and inform interventions targeting the continuum of HCV care, uptake of HCV treatment, and the impact of drug use in this population.

Incidence of noncommunicable diseases (NCDs), including cardiovascular disease (CVD), cirrhosis, and non-AIDS-defining cancers (NADCs), have been associated with HIV viremia, CD4 cell counts, and CD4/CD8 ratio in persons living with HIV (PLWH). This study examined the importance of these markers to mortality risk following NCD diagnosis. We examined factors associated with mortality following incident CVD, cirrhosis, or NADCs in a clinical cohort of PLWH between 1998 and 2015. We calculated Kaplan-Meier estimates and used multivariable Cox proportional hazard models. We included 341 patients with NCDs (CVD = 169, cancer = 103, and cirrhosis = 67), of whom 129 died. Median age at NCD diagnosis was 49 years and median proportion of time before NCD with virologic suppression was 64%. Median survival after CVD was longer than for cancer or cirrhosis (11.6 years vs. 4.8 and 3.4 years, respectively; log rank test p  < .001). In multivariable Cox proportional hazard models, higher CD4/CD8 ratio preceding NCD (adjusted hazard ratio [aHR] per 0.1 increase = 0.92 [95% confidence interval 0.85-0.99]) and higher CD4 nadir (aHR per 100 cells/μL = 0.84 [0.72-0.97]) were associated with decreased mortality risk. Neither CD4 cell count before NCD nor HIV viremia was statistically associated with mortality in adjusted models. When restricted to 116 patients with virologic suppression for ≥80% of time before NCD, only CD4 nadir was associated with mortality risk. Low CD4/CD8 ratio and CD4 nadir were associated with increased mortality risk after NCD, suggesting that prior immunosuppression or ongoing immune imbalance remain important for outcomes following serious NCDs.

Background: Although the National Comprehensive Cancer Network (NCCN) guidelines recommend use of lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) > 2 cm, there is limited evidence to support the association between use of LND and overall survival (OS)., Methods: Patients with resected pNETs were identified in the National Cancer Database (2004-2014). The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare OS of patients in different treatment groups., Results: A total of 2664 patients diagnosed met the study entry criteria. Of these, 2132 patients (80.6%) received LND, with a median of nine nodes removed. Positive nodes were identified in 28.0% of patients who underwent LND. IPTW-adjusted Kaplan-Meier analysis showed that median OS was similar between the LND and LND-omitted groups (152.8 vs. 147.3 months; p = 0.61). In IPTW-adjusted Cox proportional hazards regression analysis, LND was not associated with an OS benefit (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.94-1.42; p = 0.18). The results were consistent across subgroups stratified by clinical T and N stages. Among patients with lymph node metastasis, the number of removed nodes (NRN) above the median was not associated with an improved OS (HR 0.82, 95% CI 0.60-1.13; p = 0.22)., Conclusions: LND had no additional therapeutic benefit among patients undergoing resection for pNETs. The present findings should be considered when managing patients with resectable pNETs.

Background: Retroperitoneal sarcomas (RPS) are rare, histologically heterogeneous, and anatomically complex tumors. National Comprehensive Cancer Network guidelines recommend evaluation and management by multidisciplinary teams with experience in sarcoma. Our aim was to determine an appropriate hospital volume threshold for the treatment of RPS., Patients and Methods: Patients undergoing resection of RPS were identified from the National Cancer Data Base (1998-2012). Multivariable modeling with restricted cubic splines was employed to examine the association between hospital volume and survival and identify possible hospital volume threshold., Results: The study included 5,340 patients who underwent surgery at 909 different hospitals. Median annual volume was two cases per year. After adjustment, hospital volume was associated with improved survival (p=0.01), without cutoff. The cohort was then grouped into: Low-volume (≤5 cases/year), intermediate-volume (6-10 cases/year), and high-volume (>10 cases/year). The majority of patients were treated in low-volume hospitals (86%), compared to 9% in intermediate- and 5% in high-volume centers; 44% of patients were treated in hospitals that performed one case per year. Compared to low-volume, high-volume hospitals more often had patients with high-grade and larger tumors. Adjusted 90-day mortality was significantly lower in high- vs. low-volume hospitals (odds ratio(OR)=0.25, p=0.02). With adjustment, treatment in high- vs. low-volume hospitals was associated with lower odds of margin positivity (OR=0.58, p=0.001), and improved overall survival (hazard ratio(HR)=0.61, p=0.002)., Conclusion: Treatment of RPS in high-volume centers is associated with significant reduction in short-term mortality and improved long-term survival. Hospital volume may be a surrogate for the infrastructure and support necessary for the optimal management of these complex malignancies., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Traditional whistleblowing theories have purported that whistleblowers engage in a rational process in determining whether or not to blow the whistle on misconduct. However, stressors inherent to whistleblowing often impede rational thinking and act as a barrier to effective whistleblowing. The negative impact of these stressors on whistleblowing may be made worse depending on who engages in the misconduct: a peer or advisor. In the present study, participants are presented with an ethical scenario where either a peer or advisor engages in misconduct, and positive and the negative consequences of whistleblowing are either directed to the wrongdoer, department, or university. Participant responses to case questions were evaluated for whistleblowing intentions, moral intensity, metacognitive reasoning strategies, and positive and negative, active and passive emotions. Findings indicate that participants were less likely to report the observed misconduct of an advisor compared to a peer. Furthermore, the findings also suggest that when an advisor is the source of misconduct, greater negative affect results. Post-hoc analyses were also conducted examining the differences between those who did and did not intend to blow the whistle under the circumstances of either having to report an advisor or peer. The implications of these findings for understanding the complexities involved in whistleblowing are discussed.

Background: Retention in care (RIC) and viral suppression (VS) are associated with reduced HIV transmission and mortality. Studies addressing postpartum engagement in HIV care have been limited by small sample size, short follow-up, and a lack of data from the Southeast United States., Methods: HIV-positive adult women with ≥1 prenatal visit at the Vanderbilt Obstetrics Comprehensive Care Clinic from 1999 to 2015 were included. Poor RIC was defined as not having ≥2 encounters per year, ≥90 days apart; poor VS was a viral load >200 copies/mL. Modified Poisson regression was used to estimate adjusted relative risks (aRRs) of poor postpartum RIC and VS., Results: Among 248 women over 2070 person-years of follow-up, 37.6% person-years had poor RIC and 50.4% lacked VS. Prenatal substance use was independently associated with poor RIC (aRR, 1.40; 95% confidence interval [CI], 1.08-1.80) and poor VS (aRR, 1.20; 95% CI, 1.04-1.38), and lack of VS at enrollment was associated with poor RIC (aRR, 1.64; 95% CI, 1.15-2.35) and poor VS (aRR, 1.59; 95% CI, 1.30-1.94). Hispanic women were less likely and women with lower educational attainment were more likely to have poor RIC. Women >30 years of age and married women were less likely to have poor VS., Conclusions: In this population of women in prenatal care at an HIV primary medical home in Tennessee, women with prenatal substance use and a lack of VS at enrollment into prenatal care were at greater risk of poor RIC and lack of VS postpartum. Interventions aimed at improving postpartum engagement in HIV care among these high-risk groups are needed.

Retention in care and viral suppression are critical to delaying HIV progression and reducing transmission. Neighborhood socioeconomic context (NSEC) may affect HIV care receipt. We therefore assessed NSEC's impact on retention and viral suppression in a diverse HIV clinical cohort. HIV-positive adults with ≥1 visit at the Vanderbilt Comprehensive Care Clinic and 5-digit ZIP code tabulation area (ZCTA) information between 2008 and 2012 contributed. NSEC z-score indices used neighborhood-level socioeconomic indicators for poverty, education, labor-force participation, proportion of males, median age, and proportion of residents of black race by ZCTA. Retention was defined as ≥2 HIV care visits per calendar year, >90 days apart. Viral suppression was defined as an HIV-1 RNA <200 copies/mL at last measurement per calendar year. Modified Poisson regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI). Among 2272 and 2541 adults included for retention and viral suppression analyses, respectively, median age and CD4 count at enrollment were approximately 38 (1st and 3rd quartile: 30, 44) years and 351 (176, 540) cells/μL, respectively, while 24% were female, and 39% were black. Across 243 ZCTAs, median NSEC z-score was 0.09 (-0.66, 0.48). Overall, 79% of person-time contributed was retained and 74% was virally suppressed. In adjusted models, NSEC was not associated with retention, though being in the 4th vs. 1st NSEC quartile was associated with lack of viral suppression (RR = 0.88; 95% CI: 0.80-0.97). Residing in the most adverse NSEC was associated with lack of viral suppression. Future studies are needed to confirm this finding.

Studies evaluating the association between human immunodeficiency virus (HIV) infection continuum of care outcomes [antiretroviral (ART) adherence, retention in care, viral suppression] and health literacy have yielded conflicting results. Moreover, studies from the southern United States, a region of the country disproportionately affected by the HIV epidemic and low health literacy, are lacking. We conducted an observational cohort study among 575 people living with HIV (PLWH) at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee). Health literacy was measured using the brief health literacy screen, a short tool which can be administered verbally by trained clinical personnel. Low health literacy was associated with a lack of viral suppression, but not with poor ART adherence or poor retention. Age and racial disparities in continuum of care outcomes persisted after accounting for health literacy, suggesting that factors in addition to health literacy must be addressed in order to improve outcomes for PLWH.

Infection with the Rat Lungworm Angiostrongylus cantonensis is the leading cause of human eosinophilic meningoencephalitis worldwide. From its origins in southeastern Asia, the parasite was spread extensively throughout the twentieth century and is now established in many of the world's warmer regions. Its clinical effects range from mild and transient symptoms, usually headache with peripheral nerve dysfunction, to severe and permanent central nervous system (CNS) damage, occasionally fatal. The severity and prognosis of disease are determined by the larval dose, acquired by ingesting infected intermediate hosts (slugs and snails) or, less often, paratenic hosts, such as crabs, shrimps, frogs, and monitor lizards. Early diagnosis is critical for treatment and depends on clinical suspicion, for laboratory confirmation from blood and cerebrospinal fluid can be delayed and unreliable. Treatment is fraught with difficulty, compounded by conflicting published results. Corticosteroids play a useful role in suppressing early CNS inflammation, but their duration for maintenance becomes problematic in severe infections. Because most of the pathogenesis results from host immuno-inflammatory responses to migrating and dead larvae in the CNS, anthelminthic therapy remains controversial: if effective, it kills viable larvae, arresting them in the CNS and so exacerbating the pathology. In human infections, it is now clear that many larvae do leave the CNS and reach the pulmonary arteries, sometimes with clinical consequences. Pioneering life-cycle studies in rats demonstrated a "subarachnoid phase" in larval development and migration; recent autopsy findings, outlined here, show it also occurs in humans and has some bearing on treatment. One new and four previously reported cases of human infection are analyzed here, with findings indicating that anthelminthic treatment is effective only when given early and should not be commenced beyond 3 weeks after exposure to infection. In endemic areas, treatment should start as soon as this infection is suspected, even without a clear history of exposure, given the unacceptable risks of waiting for diagnostic laboratory confirmation.

Background: Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert's polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity., Patients and Methods: Patients had initiated atazanavir/ritonavir-containing regimens at an HIV primary care clinic in the southeastern USA, and had at least 12 months of follow-up data. Metabolizer group was defined by UGT1A1 rs887829 C→T. Genome-wide genotype data were used to adjust for genetic ancestry in combined population analyses., Results: Among 321 evaluable patients, 15 (4.6%) had bilirubin-related atazanavir discontinuation within 12 months. Homozygosity for rs887829 T/T was present in 28.1% of Black, 21.4% of Hispanic, and 8.6% of White patients. Among all patients the hazard ratio (HR) for bilirubin-related discontinuation with T/T versus C/C genotype was 7.3 [95% confidence interval (CI): 1.7-31.5; P=0.007]. Among 152 White patients the HR was 14.4 (95% CI: 2.6-78.7; P=0.002), but among 153 Black patients the HR was 0.8 (95% CI: 0.05-12.7; P=0.87)., Conclusion: Among patients who initiated atazanavir/ritonavir-containing regimens, UGT1A1 slow metabolizer genotype rs887829 T/T was associated with increased bilirubin-related discontinuation of atazanavir in White but not in Black patients, this despite T/T genotype being more frequent in Black patients.

Background: With the introduction of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy, persons living with HIV have a potent new treatment option. Recently, providers at our large treatment clinic noted weight gain in several patients who switched from efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). In this study, we evaluated weight change in patients with sustained virologic suppression who switched from EFV/TDF/FTC to an INSTI-containing regimen., Methods: We performed a retrospective observational cohort study among adults on EFV/TDF/FTC for at least 2 years who had virologic suppression. We assessed weight change over 18 months in patients who switched from EFV/TDF/FTC to an INSTI-containing regimen or a protease inhibitor (PI)-containing regimen versus those on EFV/TDF/FTC over the same period. In a subgroup analysis, we compared patients switched to DTG/ABC/3TC versus raltegravir- or elvitegravir-containing regimens., Results: A total of 495 patients were included: 136 who switched from EFV/TDF/FTC to an INSTI-containing regimen and 34 switched to a PI-containing regimen. Patients switched to an INSTI-containing regimen gained an average of 2.9 kg at 18 months compared with 0.9 kg among those continued on EFV/TDF/FTC (P = 0.003), whereas those switched to a PI regimen gained 0.7 kg (P = 0.81). Among INSTI regimens, those switched to DTG/ABC/3TC gained the most weight at 18 months (5.3 kg, P = 0.001 compared with EFV/TDF/FTC)., Conclusion: Adults living with HIV with viral suppression gained significantly more weight after switching from daily, fixed-dose EFV/TDF/FTC to an INSTI-based regimen compared with those remaining on EFV/TDF/FTC. This weight gain was greatest among patients switching to DTG/ABC/3TC.

Longitudinal studies of retention in care (RIC) and viral suppression (VS) in the southeastern United States (US), a region disproportionately affected by HIV infection, are lacking. HIV-infected adults with ≥1 medical visit at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee) from 2004 to 2013 were included. RIC was ≥2 (a) laboratory dates [CD4+ counts or HIV-1 viral loads (VLs)] or (b) provider encounters and/or laboratory dates in the year of interest, ≥90 days apart. VS was a VL of <200 copies/ml at last measurement in the year of interest. Modified Poisson regression estimated relative risk (RR) of RIC and VS, adjusting for age, race, sex, HIV transmission risk, and socioeconomic status (SES). Among 4,641 persons, 76.8% achieved RIC and 70.2% achieved VS. RIC and VS increased from 2004 to 2013 (p < .001 each). For lack of RIC, younger patients (RR = 1.2 and RR = 1.1, 18-24 and 25-34 vs. 35-44 year-olds, respectively), Blacks (RR = 1.3 vs. Whites), and injection drug users (IDUs) (RR = 1.2 vs. heterosexual contact [Hetero]) fared worse (p < .05 each); those with male-to-male sexual contact fared better (RR = 0.8 vs. Hetero, p < .05). For lack of VS, younger patients (RR = 1.3 and RR = 1.2, 18-24 and 25-34 vs. 35-44 year olds, respectively), Blacks (RR 1.3 vs. Whites), Females (RR = 1.1 vs. Males), IDUs (RR 1.3 vs. Hetero), and those with low SES (RR = 1.1 vs. not low SES) fared worse (p < .05, each). RIC and VS increased over time, suggesting that efforts to improve outcomes have been effective. However, disparities persist and resources should focus on groups most at risk.

We assessed the association between marijuana use and retention in HIV care through a retrospective cohort study of patients engaged in care at a large HIV clinic in 2011 and 2012. Two different retention outcomes were assessed: not meeting the Institute of Medicine's (IOM) retention definition (≥2 provider visits ≥90 days apart in a calendar year) and no-show visits. Any marijuana use and frequency of marijuana use were obtained from a substance use screening questionnaire administered at each clinic visit. Modified Poisson regression was used to estimate risk ratios and 95% confidence intervals for the association between marijuana use and retention outcomes. Marijuana use was reported by 17% of 1791 patients and 21% were not retained (IOM definition). Marijuana use was not associated with the IOM retention outcome, but was associated with missing the next scheduled appointment. A non-linear dose-response was observed for frequency of marijuana use and missed visits, with daily users having the highest risk compared to non-users. Daily marijuana use had a negative impact on HIV clinic attendance. Further research is needed to elucidate the mechanisms by which marijuana use affects this outcome to inform targeted interventions.

Objective: To determine the impact of race and insurance on use of minimally invasive (MIS) compared with open techniques for rectal cancer in the United States., Background: Race and socioeconomic status have been implicated in disparities of rectal cancer treatment., Methods: Adults undergoing MIS (laparoscopic or robotic) or open rectal resections for stage I to III rectal adenocarcinoma were included from the National Cancer Database (2010-2012). Multivariate analyses were employed to examine the adjusted association of race and insurance with use of MIS versus open surgery., Results: Among 23,274 patients, 39% underwent MIS and 61% open surgery. Overall, 86% were white, 8% black, and 3% Asian. Factors associated with use of open versus MIS were black race, Medicare/Medicaid insurance, and lack of insurance. However, after adjustment for patient demographic, clinical, and treatment characteristics, black race was not associated with use of MIS versus open surgery [odds ratio [OR] 0.90, P = 0.07). Compared with privately insured patients, uninsured patients (OR 0.52, P < 0.01) and those with Medicare/Medicaid (OR 0.79, P < 0.01) were less likely to receive minimally invasive resections. Lack of insurance was significantly associated with less use of MIS in black (OR 0.59, P = 0.02) or white patients (OR 0.51, P < 0.01). However, among uninsured patients, black race was not associated with lower use of MIS (OR 0.96, P = 0.59)., Conclusions: Insurance status, not race, is associated with utilization of minimally invasive techniques for oncologic rectal resections. Due to the short-term benefits and cost-effectiveness of minimally invasive techniques, hospitals may need to improve access to these techniques, especially for uninsured patients.

Background: Hypoalbuminemia is associated with adverse surgical outcomes. A minimum threshold and the impact of incrementally decreasing albumin remain undefined for colorectal surgery patients., Study Design: The 2011-2013 National Surgical Quality Improvement Program (NSQIP) dataset was queried for patients undergoing elective colorectal surgery. Multivariable regression analyses with restricted cubic splines (RCS) were used to examine the adjusted association between preoperative serum albumin level and the incidence of complications and to establish an optimal threshold. RCS allows for flexible evaluation in multivariable models without having to assume a specific relationship a priori., Results: Sixteen thousand one hundred forty-five patients met study criteria. RCS analysis demonstrated an inflection point at serum albumin level of 3.9 mg/dL. Patients with preoperative albumin <3.9 mg/dL vs. albumin ≥3.9 mg/dL had a higher likelihood of experiencing a major complication (odds ratio (OR) = 1.18, confidence interval (CI) 1.07-1.30, p = 0.0007) or any complications (OR 1.18, CI 1.08-1.29, p = 0.0002,) and had a lengthened hospital stay (p < 0.001)., Conclusions: This study objectively determines that a threshold preoperative serum albumin of ≥3.9 mg/dL is associated with improved outcomes in elective colorectal surgery patients. Each 0.5 mg/dL decrease in albumin was progressively associated with increased risk for complications. Identifying a minimum albumin threshold has implications in perioperative optimization of patients undergoing colorectal surgery.

Background: Efavirenz frequently causes central nervous system (CNS) symptoms. We evaluated genetic associations with efavirenz discontinuation for CNS symptoms within 12 months of treatment initiation., Methods: Patients had initiated efavirenz-containing regimens at an HIV primary care clinic in the Southeastern United States and had at least 12 months of follow-up data. Polymorphisms in CYP2B6 and CYP2A6 defined efavirenz metabolizer categories. Genome-wide genotyping enabled adjustment for population stratification., Results: Among 563 evaluable patients, 99 (17.5%) discontinued efavirenz within 12 months, 29 (5.1%) for CNS symptoms. The hazard ratio (HR) for efavirenz discontinuation for CNS symptoms in slow versus extensive metabolizers was 4.9 [95% confidence interval (CI): 1.9-12.4; P=0.001]. This HR in Whites was 6.5 (95% CI: 2.3-18.8; P=0.001) and 2.6 in Blacks (95% CI: 0.5-14.1; P=0.27). Considering only slow metabolizers, the HR in Whites versus Blacks was 3.1 (95% CI: 0.9-11.0; P=0.081). The positive predictive value of slow metabolizer genotypes for efavirenz discontinuation was 27% in Whites and 11% in Blacks., Conclusion: Slow metabolizer genotypes were associated significantly with efavirenz discontinuation for reported CNS symptoms. This association was considerably stronger in Whites than in Blacks.

Objective: In virologically suppressed HIV-infected adults, noncommunicable diseases (NCDs) have been associated with immune senescence and low CD4/CD8 lymphocyte ratio. Age differences in the relationship between CD4/CD8 ratio and NCDs have not been described., Design: Observational cohort study., Methods: We assessed CD4/CD8 ratio and incident NCDs (cardiovascular, cancer, liver, and renal diseases) in HIV-infected adults started on antiretroviral therapy between 1998 and 2012. Study inclusion began once patients maintained virologic suppression for 12 months (defined as baseline). We examined age and baseline CD4/CD8 ratio and used Cox proportional hazard models to assess baseline CD4/CD8 ratio and NCDs., Results: This study included 2006 patients. Low baseline CD4/CD8 ratio was associated with older age, male sex, and low CD4 lymphocyte counts. In models adjusting for CD4 lymphocyte count, CD4/CD8 ratio was inversely associated with age (P < 0.01). Among all patients, 182 had incident NCDs, including 46 with coronary artery disease (CAD) events. CD4/CD8 ratio was inversely associated with risk of CAD events [adjusted HR per 0.1 increase in CD4/CD8 ratio = 0.87, 95% confidence interval (CI): 0.76-0.99, P = 0.03]. This association was driven by those under age 50 years (adjusted HR 0.83 [0.70-0.97], P = 0.02) vs. those over age 50 years (adjusted HR = 0.96 [0.79-1.18], P = 0.71). CD4/CD8 ratio was not significantly associated with incident noncardiac NCDs., Conclusions: Higher CD4/CD8 ratio after 1 year of HIV virologic suppression was independently predictive of decreased CAD risk, particularly among younger adults. Advanced immune senescence may contribute to CAD events in younger HIV patients on antiretroviral therapy.

In the United States (USA), the age of those newly diagnosed with HIV is changing, particularly among men who have sex with men (MSM). A retrospective analysis included HIV-infected adults from seven sites in the Caribbean, Central and South America network (CCASAnet) and the Vanderbilt Comprehensive Care Clinic (VCCC-Nashville, Tennessee, USA). We estimated the proportion of patients <25 years at HIV diagnosis by calendar year among the general population and MSM. 19,466 (CCASAnet) and 3,746 (VCCC) patients were included. The proportion <25 years at diagnosis in VCCC increased over time for both the general population and MSM (p < 0.001). Only in the Chilean site for the general population and the Brazilian site for MSM were similar trends seen. Subjects <25 years of age at diagnosis were less likely to be immunocompromised at enrollment at both the VCCC and CCASAnet. Recent trends in the USA of greater numbers of newly diagnosed young patients were not consistently observed in Latin America and the Caribbean. Prevention efforts tailored to young adults should be increased.

Background: Hormonal contraception use is common among human immunodeficiency virus (HIV)-infected women. Risk of psychiatric and other noninfectious complications of hormonal contraception use has not been described in this population., Methods: We performed a retrospective cohort study of HIV-infected women receiving care in Tennessee from 1998 to 2008 to examine the risks of incident psychiatric and other noncommunicable diseases (NCDs), including cardiovascular, hepatic, renal, and malignant diseases, and hormonal contraception use, including depot medroxyprogesterone acetate (DMPA) and combined estrogen- and progestin-containing hormonal contraceptives. We used marginal structural models with inverse probability weights to account for time-varying confounders associated with hormonal contraception use., Results: Of the 392 women included, 94 (24%) used hormonal contraception during the study period. Baseline psychiatric disease was similar between women who received and did not receive hormonal contraception. There were 69 incident psychiatric diagnoses and 72 NCDs. Only time-varying DMPA use was associated with increased risk of psychiatric disease (adjusted odds ratio [aOR] 3.70; 95% confidence interval [95% CI] 1.32-10.4) and mood disorders, specifically (aOR 4.70 [1.87-11.8]). Time-varying and cumulative combined hormonal contraception use were not statistically associated with other NCDs (aOR 1.64, 95% CI 0.64-4.12 and aOR 1.16, 95% CI 0.86-1.56, respectively). However, risk of incident NCDs was increased with cumulative DMPA exposure (per year exposure aOR 1.45, 95% CI 1.01-2.08)., Conclusions: Among HIV-infected women, DMPA was associated with risk of incident psychiatric diseases, particularly mood disorders, during periods of use. Cumulative DMPA exposure was also associated with risk of other NCDs. However, combined estrogen and progestin-containing hormonal contraception use was not statistically associated with risk of any NCDs.

Background: With successful antiretroviral therapy, non-communicable diseases, including malignancies, are increasingly contributing to morbidity and mortality among HIV-infected persons. The epidemiology of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) in HIV-infected populations in Brazil has not been well described. It is not known if cancer trends in HIV-infected populations in Brazil are similar to those of other countries where antiretroviral therapy is also widely available., Methods: We performed a retrospective analysis of clinical cohorts at Instituto Nacional de Infectologia Evandro Chagas (INI) in Rio de Janeiro and Vanderbilt Comprehensive Care Clinic (VCCC) in Nashville from 1998 to 2010. We used Poisson regression and standardized incidence ratios (SIRs) to examine incidence trends. Clinical and demographic predictors of ADCs and NADCs were examined using Cox proportional hazards models., Results: This study included 2,925 patients at INI and 3,927 patients at VCCC. There were 57 ADCs at INI (65% Kaposi sarcoma), 47 at VCCC (40% Kaposi sarcoma), 45 NADCs at INI, and 82 at VCCC. From 1998 to 2004, incidence of ADCs remained statistically unchanged at both sites. From 2005 to 2010, ADC incidence decreased in both cohorts (INI incidence rate ratio per year = 0.74, p < 0.01; VCCC = 0.75, p < 0.01). Overall Kaposi sarcoma incidence was greater at INI than VCCC (3.0 vs. 1.2 cases per 1,000 person-years, p < 0.01). Incidence of NADCs remained constant throughout the study period (overall INI incidence 3.6 per 1,000 person-years and VCCC incidence 5.3 per 1,000 person-years). Compared to general populations, overall risk of NADCs was increased at both sites (INI SIR = 1.4 [95% CI 1.1-1.9] and VCCC SIR = 1.3 [1.0-1.7]). After non-melanoma skin cancers, the most frequent NADCs were anal cancer at INI (n = 7) and lung cancer at VCCC (n = 11). In multivariate models, risk of ADC was associated with male sex and immunosuppression. Risk of NADC was associated with increased age., Conclusions: In both cohorts, ADCs have decreased over time, though incidence of KS was higher at INI than VCCC. Rates of NADCs remained constant over time at both sites.

Obesity and chronic, treated HIV infection are both associated with persistent systemic inflammation and a similar constellation of metabolic and cardiovascular diseases, but the combined effects of excess adiposity and HIV on circulating proinflammatory cytokines and other biomarkers previously shown to predict disease risk is not well described. We measured inflammation biomarker levels in 158 predominantly virologically suppressed adults on long-term antiretroviral therapy (ART) with a range of body mass index (BMI) values from normal to morbidly obese. We assessed the relationship between BMI and each biomarker using multivariable linear regression adjusted for age, sex, race, CD4(+) count, tobacco use, data source, protease inhibitor use, and routine nonsteroidal antiinflammatory drug (NSAID) or aspirin use. Among normal-weight (n=48) and overweight participants (n=41; BMI <30 kg/m(2)), incremental BMI increases were associated with significantly higher serum highly sensitive C-reactive protein (hsCRP; β=2.47, p=0.02) and tumor necrosis factor (TNF)-α receptor 1 levels (β=1.53, p=0.03), and significantly lower CD14 levels (β=0.84, p=0.01), but similar associations were not observed in the obese participants. Among the obese (n=69; BMI ≥30 kg/m(2)), however, higher serum levels of interleukin-6 (IL-6; β=1.30, p=0.02) and macrophage inflammatory protein-1α (β=1.77, p<0.01) were associated with higher BMI, a finding not observed among the nonobese. Among all participants, IL-6 and TNF-α receptor 1 levels were most closely associated with hsCRP (p<0.01). Further studies are needed to determine whether higher serum inflammation biomarker levels found in obese HIV-infected individuals on ART reflect an increased likelihood of adverse health outcomes, or if novel markers to estimate mortality and disease risk are needed in this population.