Alcohol and drug use severity are independently associated with antiretroviral adherence in the current treatment era.

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.

A COVID-19 monitoring process for healthcare workers utilizing occupational health.

BACKGROUND: Hospital-based occupational health (HBOH) is uniquely positioned to not only prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, but to care for healthcare workers (HCWs) sick with coronavirus disease 2019 (COVID-19). AIMS: The primary objective of this study is to describe a system where HBOH services were adapted to provide a monitoring programme whereby HCWs with SARS-CoV-2 received daily evaluations and treatment options in order to improve access to care, and to report the clinical outcomes and predictors of hospitalization in HCWs enrolled in the programme. A secondary objective is to compare clinical outcomes to data on national HCWs with COVID-19. METHODS: This retrospective cohort study used survey data collected on HCWs at a university health system with COVID-19 from 1 March 2020 through 1 December 2021. A firth regression model was used to examine the unadjusted and adjusted association between clinical factors and hospitalization. RESULTS: The study cohort included 4814 HCWs with COVID-19. Overall hospitalizations were 119 (2%), and there were six deaths (0.12%). Predictors of hospitalization include several co-morbidities and symptoms. A total of 1835 HCWs monitored before vaccine or monoclonal antibody availability were compared with data on U.S. HCWs in a similar time period. The monitored HCWs had a lower rate of co-morbidities (19% versus 44%, P < 0.001), a lower hospitalization rate (3% versus 8% P < 0.001) and case-fatality rate (0.11% versus 0.95% P < 0.001). CONCLUSIONS: This monitoring strategy for COVID-19 may be feasible for HBOH systems to implement and improve access to care, but more data are needed to determine if it improves outcomes.

Anemia risk factors among people living with HIV across the United States in the current treatment era: a clinical cohort study.

BACKGROUND: Anemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking. METHODS: Within a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site. RESULTS: This retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3-7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR. CONCLUSION: Because anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.

Lessons learned from the design and implementation of myocardial infarction adjudication tailored for HIV clinical cohorts.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Racial and ethnic disparities in COVID-19 disease incidence independent of comorbidities, among people with HIV in the US.

OBJECTIVES: To define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200; 95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count <350 (proxy for CD4 nadir), current low CD4/CD8 ratio, diabetes, and obesity. CONCLUSIONS: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.

The effects of sodium and magnesium-ion interactions on chromatin structure and solubility.

The effects of sodium and magnesium-ion interactions on chromatin structure and solubility were examined in isolated mouse liver nuclei. To facilitate this study, a simple assay of chromatin structure was developed, based on the absorbances at 260 nm (A260) and 320 nm (A320) of nuclei in test solutions. By subtracting the A320 from the A260, a single "spectral index" was obtained which served as a useful, but not absolute, indicator of chromatin structure. Electron microscopy verified the validity of this approach. The results indicate that either 200 mM NaCl or 0.5 mM MgCl2 were capable of preserving the native 20 to 30 nm chromatin fiber structure. Below 200 mM NaCl, the native fiber progressively uncoiled to the 10 nm unit fiber. The presence of 0.5 mM MgCl2 inhibited this uncoiling. Only divalent cations stabilized condensed chromatin (heterochromatin) within the nucleus. Monovalent and divalent cations interacted with one another at critical concentrations and modified their individual effects on chromatin structure; e.g., 10 to 25 mM NaCl interfered with the action of 0.5 to 1.5 mM MgCl2, causing a complete loss of condensed chromatin. Maximum solubility of micrococcal nuclease-digested chromatin occurred at 10 mM NaCl, which treatment allowed the chromatin to unfold to the 10 nm fiber. However, ionic conditions that disrupted condensed chromatin but maintained the native chromatin fiber morphology still resulted in relatively high yields of soluble chromatin. Minimum solubility occurred under conditions which preserved the structure of condensed chromatin.

Triplex DNA in plasmids and chromosomes.

Circular plasmids containing pyrimidine purine tracts can form both inter-and intramolecular triplexes. Addition of poly(dTC) to plasmid pTC45, which contains a (TC)45.(GA)45 insert, results in intermolecular triplex formation. Agarose-gel electrophoresis gives rise to many well-resolved bands, which correspond to 1, 2, 3, 4... plasmid molecules attached to the added pyrimidine strand. In the electron microscope these complexes appear as a rosette of petals. The mobility of these triplex-containing complexes can be retarded by the addition of a triplex-specific monoclonal antibody, Jel318. Intramolecular triplex formation can be demonstrated at pH 5 in pTC45 and also in pT463-I, a plasmid containing a segment of a crab satellite DNA with both (G)n.(C)n and (TCC)n.(GGA)n inserts. However, although the intermolecular triplex remains stable for some time at pH 8, intramolecular triplex formation only occurs at low pH. Triplexes can also be detected by an immunoblotting procedure with Jel318. This unfamiliar structure is readily demonstrated in eukaryotic extracts, but not in cell extracts from Escherichia coli. Triplexes may thus be an inherent feature of eukaryotic chromosome structure.

Sexual Assertiveness Scale (SAS) for women: development and validation.

Four studies were conducted to develop and validate the Sexual Assertiveness Scale (SAS), a measure of sexual assertiveness in women that consists of factors measuring initiation, refusal, and pregnancy-sexually transmitted disease prevention assertiveness. A total of 1,613 women from both university and community populations were studied. Confirmatory factor analyses demonstrated that the 3 factors remained stable across samples of university and community women. A structural model was tested in 2 samples, indicating that sexual experience, anticipated negative partner response, and self-efficacy are consistent predictors of sexual assertiveness. Sexual assertiveness was found to be somewhat related to relationship satisfaction, power, and length. The community sample was retested after 6 months and 1 year to establish test-retest reliability. The SAS provides a reliable instrument for assessing and understanding women's sexual assertiveness.

PIP: The construct of sexual assertiveness has potential for codifying the strategies women use to achieve sexual autonomy. The Sexual Assertiveness Scale (SAS) was developed to measure initiation of wanted sexual experience, refusal of unwanted sexual experience, and prevention of pregnancy and sexually transmitted diseases (STDs) with a regular partner. Four independent studies were conducted to establish the stability of the factor structure of the SAS, evaluate the set of predictors of sexual assertiveness, further assess construct validity in a population at high risk of STDs, and test reliability through two follow-ups. A total of 1613 US women from university and community populations were included in the studies. Confirmatory factor analyses indicated that Initiation, Refusal, and Pregnancy/STD Prevention remained stable across samples. Consistent predictors of sexual assertiveness were sexual experience, anticipated negative partner response, a history of sexual victimization as an adolescent or adult, and self-efficacy. Relationship satisfaction, power, and length were moderately related to sexual assertiveness. Finally, test-retest reliability was confirmed. Use of the SAS could facilitate the design of programs to help women to become more able to negotiate condom use, for example.

Distal splenorenal (Warren) shunt following nephrectomy for renal cell carcinoma: case report.

A 61-year-old man, who had previously undergone a mesocaval shunt for recurrent bleeding from esophageal varices secondary to portal hypertension and cirrhosis of the liver, experienced postoperative hemorrhage, again from esophageal varices. Angiographic evaluation of the thrombosed mesocaval shunt revealed an unanticipated left renal cell carcinoma, which was treated with radical left nephrectomy. The left renal vein was then anastomosed to the splenic vein, end-to-side fashion. The splenic vein was ligated at its junction with the superior mesenteric vein to affect a dital splenorenal (Warren) shunt. Pressure within the patient's splenic vein was reduced from 35 to 25 cm H2O. Grossly, and ultimately histologically, there was no evidence of tumor within the left renal vein. The patient made an uneventful recovery and has experienced no further bleeding from esophageal varices.