Pharmacogenetics of interaction between depot medroxyprogesterone acetate and efavirenz, rifampicin, and isoniazid during treatment of HIV and tuberculosis.

OBJECTIVE: In AIDS Clinical Trials Group study A5338, concomitant rifampicin, isoniazid, and efavirenz was associated with more rapid plasma medroxyprogesterone acetate (MPA) clearance compared to historical controls without tuberculosis or HIV therapy. We characterized the pharmacogenetics of this interaction. METHODS: In A5338, women receiving efavirenz-based HIV therapy and rifampicin plus isoniazid for tuberculosis underwent pharmacokinetic evaluations over 12 weeks following a 150-mg intramuscular injection of depot MPA. Data were interpreted with nonlinear mixed-effects modelling. Associations between individual pharmacokinetic parameters and polymorphisms relevant to rifampicin, isoniazid, efavirenz, and MPA were assessed. RESULTS: Of 62 A5338 participants in four African countries, 44 were evaluable for pharmacokinetic associations, with 17 CYP2B6 normal, 21 intermediate, and 6 poor metabolizers, and 5 NAT2 rapid, 20 intermediate, and 19 slow acetylators. There were no associations between either CYP2B6 or NAT2 genotype and MPA Cmin at week 12, apparent clearance, Cmax, area under the concentration-time curve (AUC) or half-life, or unexplained interindividual variability in clearance, and uptake rate constant or mean transit time of the slow-release fraction (P > 0.05 for each). In exploratory analyses, none of 28 polymorphisms in 14 genes were consistently associated with MPA pharmacokinetic parameters, and none withstood correction for multiple testing. CONCLUSIONS: Study A5338 suggested that more frequent depot MPA dosing may be appropriate for women receiving rifampicin, isoniazid, and efavirenz. The present results suggest that knowledge of CYP2B6 metabolizer or NAT2 acetylator status does not inform individualized DMPA dosing in this setting.

Using the multiphase optimization strategy (MOST) framework to optimize an intervention to increase COVID-19 testing for Black and Latino/Hispanic frontline essential workers: A study protocol.

BACKGROUND: Among those at highest risk for COVID-19 exposure is the large population of frontline essential workers in occupations such food service, retail, personal care, and in-home health services, among whom Black and Latino/Hispanic persons are over-represented. For those not vaccinated and at risk for exposure to COVID-19, including frontline essential workers, regular (approximately weekly) COVID-19 testing is recommended. However, Black and Latino/Hispanic frontline essential workers in these occupations experience serious impediments to COVID-19 testing at individual/attitudinal- (e.g., lack of knowledge of guidelines), social- (e.g., social norms), and structural-levels of influence (e.g., poor access), and rates of testing for COVID-19 are insufficient. METHODS/DESIGN: The proposed community-engaged study uses the multiphase optimization strategy (MOST) framework and an efficient factorial design to test four candidate behavioral intervention components informed by an integrated conceptual model that combines critical race theory, harm reduction, and self-determination theory. They are A) motivational interview counseling, B) text messaging grounded in behavioral economics, C) peer education, and D) access to testing (via navigation to an appointment vs. a self-test kit). All participants receive health education on COVID-19. The specific aims are to: identify which components contribute meaningfully to improvement in the primary outcome, COVID-19 testing confirmed with documentary evidence, with the most effective combination of components comprising an "optimized" intervention that strategically balances effectiveness against affordability, scalability, and efficiency (Aim 1); identify mediators and moderators of the effects of components (Aim 2); and use a mixed-methods approach to explore relationships among COVID-19 testing and vaccination (Aim 3). Participants will be N = 448 Black and Latino/Hispanic frontline essential workers not tested for COVID-19 in the past six months and not fully vaccinated for COVID-19, randomly assigned to one of 16 intervention conditions, and assessed at 6- and 12-weeks post-baseline. Last, N = 50 participants will engage in qualitative in-depth interviews. DISCUSSION: This optimization trial is designed to yield an effective, affordable, and efficient behavioral intervention that can be rapidly scaled in community settings. Further, it will advance the literature on intervention approaches for social inequities such as those evident in the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05139927 ; Registered on 11/29/2021. Protocol version 1.0. May 2, 2022, Version 1.0.

An Overview of Long COVID Support Services in Australia and International Clinical Guidelines, With a Proposed Care Model in a Global Context.

Objective: To identify gaps among Australian Long COVID support services and guidelines alongside recommendations for future health programs. Methods: Electronic databases and seven government health websites were searched for Long COVID-specific programs or clinics available in Australia as well as international and Australian management guidelines. Results: Five Long COVID specific guidelines and sixteen Australian services were reviewed. The majority of Australian services provided multidisciplinary rehabilitation programs with service models generally consistent with international and national guidelines. Most services included physiotherapists and psychologists. While early investigation at week 4 after contraction of COVID-19 is recommended by the Australian, UK and US guidelines, this was not consistently implemented. Conclusion: Besides Long COVID clinics, future solutions should focus on early identification that can be delivered by General Practitioners and all credentialed allied health professions. Study findings highlight an urgent need for innovative care models that address individual patient needs at an affordable cost. We propose a model that focuses on patient-led self-care with further enhancement via multi-disciplinary care tools.

Exploring the relationship between religious service attendance, mental disorders, and suicidality among different ethnic groups: results from a nationally representative survey.

BACKGROUND: To date, sufficient data have not been available to examine ethnic differences in religiosity and mental health in the general population. However, evidence exists to suggest that the protective effects of religion may differ across ethnic groups. This study examined the relationship between religious attendance and mental health across ethnic groups. METHODS: The Collaborative Psychiatric Epidemiologic Survey (N = 20,130) is a large, ethnically diverse sample of adult, US respondents. Frequency of attendance at religious services was measured as: at least once per week (reference group), one to three times per month, less than once per month, or less than once per year. Multiple logistic regression analyses examined associations between religious attendance and mood, anxiety and substance use disorders, as well as suicidal ideation and attempts. Models adjusted for sociodemographics and comorbidity. RESULTS: Results differed when performed within each ethnicity. Infrequent religious attendance was associated with substance use disorders in Whites and Africans only (Adjusted Odds Ratio (AOR) = 2.30 [95% CI = 1.77-2.99]; AOR = 1.86 [1.25-2.79], respectively), and with anxiety and suicidal ideation in Whites (AOR = 1.44 [1.10-1.88]; AOR = 1.58 [1.24-2.01]) and Hispanics only (AOR = 2.35 [1.17-4.73]; AOR = 1.70 [1.15-2.52]). Asians were the only group in which religious attendance was associated with mood disorders (AOR = 4.90 [1.54-15.60]). Interaction terms were nonsignificant. CONCLUSIONS: The present study suggests that ethnicity is an important variable to consider in the relationship between religiosity and mental health. Future studies should attempt to either adjust for or stratify by ethnicity when examining these relationships.

Contraception for the HIV-positive woman: a review of interactions between hormonal contraception and antiretroviral therapy.

BACKGROUND: Preventing unintended pregnancy in HIV-positive women can significantly reduce maternal-to-child HIV transmission as well as improve the woman's overall health. Hormonal contraceptives are safe and effective means to avoid unintended pregnancy, but there is concern that coadministration of antiretroviral drugs may alter contraceptive efficacy. MATERIALS AND METHODS: We performed a literature search of PubMed and Ovid databases of articles published between January 1980 and February 2012 to identify English-language reports of drug-drug interactions between hormonal contraceptives (HCs) and antiretroviral drugs (ARVs). We also reviewed the FDA prescribing information of contraceptive hormone preparations and antiretrovirals for additional data and recommendations. RESULTS: Twenty peer-reviewed publications and 42 pharmaceutical package labels were reviewed. Several studies of combined oral contraceptive pills (COCs) identified decreased serum estrogen and progestin levels when coadministered with certain ARVs. The contraceptive efficacy of injectable depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) were largely unaffected by ARVs, while data on the contraceptive patch, ring, and implant were lacking. CONCLUSIONS: HIV-positive women should be offered a full range of hormonal contraceptive options, with conscientious counseling about possible reduced efficacy of COCs and the contraceptive implant when taken with ARVs. DMPA and the LNG-IUS maintain their contraceptive efficacy when taken with ARVs.

The effect of Avoidant Personality Disorder on the persistence of Generalized Social Anxiety Disorder in the general population: results from a longitudinal, nationally representative mental health survey.

BACKGROUND: The primary objective of this study was to prospectively examine the role of Avoidant Personality Disorder (AvPD) as a determinant in the outcome of Generalized Social Anxiety Disorder (GSAD) using Wave 2 of the National Epidemiologic Survey of Alcohol and Related Conditions 3 years later. METHOD: This study analyzed data from Waves 1 and 2 of the NESARC (n = 34,653). GSAD was operationalized based on the DSM-IV definitions of this SAD subtype. RESULTS: Logistic regression analyses indicated that AvPD significantly predicted the persistence of GSAD, even after adjusting for a number of important sociodemographic variables and other psychiatric comorbidity. AvPD did not significantly predict outcome in non-generalized SAD. CONCLUSIONS: AvPD can influence the course of GSAD in adulthood. Specific personality dimensions may underlie and explain the similarities between AvPD and GSAD. Self-criticism could be a shared feature of both AvPD and GSAD and could represent an important psychological marker of poor prognosis in comorbid GSAD and AvPD.

Oral sedation for pain with cervical dilator placement: a randomized controlled trial.

OBJECTIVE: Assess oral sedation versus placebo for pain control with cervical dilator placement. STUDY DESIGN: We randomized participants presenting for dilation and evacuation to lorazepam 1 mg/oxycodone 5 mg or placebo 45 min before cervical dilator placement. Our primary outcome was median visual analog scale (VAS) pain score after dilator placement using a 100-mm VAS. We used our outcome data to calculate median pain score changes from baseline to better reflect pain score differences between study groups. Planned sample size was 30 participants per group, for a total of 60. RESULTS: We randomized 27 participants; 9 received sedation and 11 placebo. Median pain score increase from baseline to last dilator placement was 20 [interquartile range (IQR) 8-29] and 31 (IQR 15-81) in the oral sedation and placebo groups, p = .16. CONCLUSION: We were unable to enroll our desired sample size, and our sample is underpowered to make any conclusions. Our results suggest that oral sedation may provide some benefit for pain relief with dilator insertion and indicate that further research might be worthwhile especially in settings that do not routinely provide these analgesics. IMPLICATIONS: We had difficulty with study recruitment because many patients desired oral sedation for pain management for cervical dilator placement and declined randomization. Randomized trials of pain management with a placebo arm may find recruitment challenging especially if default clinical care already includes a pain management option that patients would have to opt out of.

"Thanks for hearing me out": Voices of social work students during COVID-19.

As social work educators and students, the COVID-19 pandemic impacted our teaching and learning in challenging ways. We embarked on a qualitative research study to better understand the ways in which the pandemic was affecting the social work students in our program. Three faculty mentors worked collaboratively with five social work students across BSW, MSW, and PhD programs to interview 66 BSW and MSW students about their experiences, challenges, and hopes during the early months of the pandemic. BSW and MSW students led the analysis and early dissemination for the project. This essay describes the unique experiences of social work students by using a research poem to capture the emotional and experiential aspects of the students we interviewed.

Correlates of self-medication for anxiety disorders: results from the National Epidemiolgic Survey on Alcohol and Related Conditions.

Self-medication is a common behavior among individuals with anxiety disorders, yet few studies have examined the correlates of this behavior. The current study addresses this issue by exploring the pattern of mental health service use and quality of life among people who self-medicate for anxiety. Data came from the National Epidemiologic Survey on Alcohol and Related Conditions and was limited to the subsample of individuals meeting criteria for an anxiety disorder in the past 12 months (n = 4880). Multiple regression analyses compared 3 groups-(1) no self-medication, (2) self-medication with alcohol, and (3) self-medication with drugs, on mental health service use and quality of life. After adjusting for potentially confounding covariates, individuals who engaged in self-medication had significantly higher service use compared with people with anxiety disorders who did not self-medicate (adjusted odds ratio = 1.41, 95% CI = 1.06-1.89). Self-medication was also associated with a lower mental health-related quality of life compared with those who did not self-medicate. Clinicians should recognize and respond to the unique needs of this particular subpopulation of individuals with anxiety disorders.

Comparison of the Pharmacokinetics and Pharmacodynamics of Single-Dose Tenofovir Vaginal Film and Gel Formulation (FAME 05).

OBJECTIVE: Although preexposure prophylaxis with oral tenofovir (TFV) disoproxil fumarate/emtricitabine reduces HIV acquisition rates, poor adherence to and acceptability of daily vaginal gels have led to development of vaginal film formulations to improve adherence and, potentially, to enable episodic use. STUDY DESIGN: In this 2-arm, cross-over study of a fast-dissolving tenofovir film (40 mg) compared with a previously studied semisolid tenofovir 1% gel (40 mg), 10 healthy women received a single vaginal dose of each study product. Clinical, pharmacokinetic, and antiviral assessments were performed over 1 week after dose. RESULTS: Nine of 10 participants experienced mild to moderate adverse effects, similar between products, with no severe adverse events or events attributed to study products. TFV concentrations after film dosing exceeded concentrations after gel dosing in plasma between 8 and 24 hours (P ≤ 0.02). TFV concentrations in cervicovaginal fluid and both TFV and TFV diphosphate concentrations in cervical tissue homogenates were higher after film dosing (all P values < 0.04). The differences ranged from median (interquartile range) 2.9-fold (1.1, 9.0; midvaginal cervicovaginal fluid) to 4.4-fold (2.9, 7.7; plasma). Neither film nor gel demonstrated reduced cervical tissue biopsy infectivity after ex vivo HIV challenge. CONCLUSION: Single-dose tenofovir film demonstrated consistently higher concentrations in plasma and cervicovaginal samples when compared with gel during the first day after dosing. Single-dose cervical tissue TFV-diphosphate concentrations at 5 hours exceeded steady-state concentrations previously reported with daily oral Truvada dosing. Tenofovir film may provide an alternative to tenofovir oral and gel formulations. Clinical efficacy remains to be tested.

Effective media communication of disasters: pressing problems and recommendations.

BACKGROUND: Public health officials and journalists play a crucial role in disseminating information regarding natural disasters, terrorism and other human-initiated disasters. However, research suggests that journalists are unprepared to cover terrorism and many types of natural disasters, in part because of lack sufficient expertise in science and medicine and training. The objective of this research was to identify solutions to problems facing journalists and public health public information officer (PIOs) of communicating with the public during natural and human-initiated disasters. METHODS: To assist in identifying the most pressing problems regarding media response to health-related risks such as terrorism and large-scale natural disasters, 26 expert advisors were convened, including leaders representing journalists and public information officers, state health officials, experts in terrorism and emergency preparedness, and experts in health, risk, and science communication. The advisory group participated in pre-arranged interviews and were asked to identify and review bioterrorism educational resources provided to journalist. All advisory group members were then invited to attend a day long meeting January 29, 2004 to review the findings and reach consensus. RESULTS: The most pressing problems were found to be a lack of coordination between PIO's and journalists, lack of resources for appropriately evaluating information and disseminating it efficiently, and a difference in perception of PIO's and journalist towards each others role during emergency situations. The advisory board developed a list of 15 recommendations that may enhance communication plans between PIO's, journalist and the public. The solutions were meant to be feasible in terms of costs and practical in terms of the professional and organizational realities in which journalists and PIO's work. CONCLUSION: It is clear that PIO's and journalists play crucial roles in shaping public response to terrorism and other disasters. The findings from this formative research suggest that perspectives and organizational processes often limit effective communication between these groups; though practical solutions such as participation of journalists in drills, scenario exercises, sharing of informational resources, and raising awareness at professional trade meetings may enhance the timely dissemination of accurate and appropriate information.

Comparison of Dapivirine Vaginal Gel and Film Formulation Pharmacokinetics and Pharmacodynamics (FAME 02B).

While preexposure prophylaxis with oral tenofovir/emtricitabine reduces HIV acquisition rates, poor adherence to and acceptability of vaginal gels and the potential for evolving drug resistance have led to development of vaginal film formulations and other antiretroviral drugs, respectively, including the non-nucleoside reverse transcriptase inhibitor dapivirine. In this two-arm crossover study of a novel fast-dissolving dapivirine film and a previously studied semisolid dapivirine gel, 10 healthy women received a single 1.25 mg vaginal dose of each study product; one withdrew after the first dose. Clinical, pharmacokinetic, and antiviral pharmacodynamic assessments (ex vivo HIV-BaL challenge of tissue explants) were performed over 168 h postdose. Six of ten participants experienced mild to moderate adverse effects, similar between products, with no severe adverse events or adverse events attributed to study products. There were no statistically significant differences in plasma, cervicovaginal fluid (CVF), or cervical tissue dapivirine concentrations between the gel and film (all p > .05). CVF dapivirine concentrations were 1.5 and 6 log10 greater than tissue and plasma concentrations, respectively (p < .001). Both film and gel demonstrated reduced cervical tissue infectivity after ex vivo HIV challenge 5 h postdose, compared to baseline and 72-h postdose biopsies (p < .05 for gel, p = .06 for film). There was no difference in ex vivo explant HIV challenge between gel and film. The dapivirine film and gel performed similarly in terms of tolerability, pharmacokinetics, and antiviral effect. Dapivirine film may provide an alternative to pharmacokinetically comparable dapivirine gel formulations. Effectiveness remains to be tested.

Obesity and hormonal contraceptive efficacy.

Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.

A longitudinal investigation of the role of self-medication in the development of comorbid mood and drug use disorders: findings from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

OBJECTIVE: To examine whether self-medication with drugs confers risk of comorbid mood and drug use disorders. METHOD: A longitudinal, nationally representative survey was conducted by the National Institute on Alcohol Abuse and Alcoholism. The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) assessed DSM-IV-TR psychiatric disorders, self-medication, and sociodemographic variables at 2 time points. A total of 34,653 adult, US participants completed both waves of the survey. Wave 1 was conducted between 2001 and 2002, and Wave 2 interviews took place 3 years later (2004-2005). Logistic regression and population attributable fractions were calculated to obtain estimates of the association between self-medication and incident disorders. RESULTS: Logistic regression analyses revealed that self-medication with drugs conferred a heightened risk of new-onset drug dependence among those with baseline mood disorders (adjusted odds ratio [AOR] = 7.65; 95% CI, 3.70-15.82; P < .001) and accounted for over 25% of incident drug dependence disorders among people with mood disorders. Among those with comorbid mood and drug use disorders at baseline, self-medication with drugs was associated with the persistence of drug abuse (AOR = 2.47; 95% CI, 1.34-4.56; P < .01), accounting for over one-fifth of the persistence of drug use disorders at 3-year follow-up. CONCLUSIONS: Self-medication with drugs among individuals with mood disorders confers substantial risk of developing incident drug dependence and is associated with the persistence of comorbid mood and drug use disorders. These results clarify a pathway that may lead to the development of mood and drug use disorder comorbidity and indicate an at-risk population, with potential points of intervention for prevention of comorbidity.

Longitudinal relationships of religious worship attendance and spirituality with major depression, anxiety disorders, and suicidal ideation and attempts: findings from the Baltimore epidemiologic catchment area study.

We present findings on the longitudinal relationships of religious worship attendance and seeking spiritual comfort with subsequent major depression, anxiety disorders and suicidal ideation/attempts using data from Waves 3 and 4 of the Baltimore Epidemiologic Catchment Area Study (N = 1091). Respondents who attended religious services at least once per year had decreased odds of subsequent suicide attempts compared with those who did not attend religious services (AOR = 0.33, 95% CI: 0.13-0.84). Seeking spiritual comfort at baseline was associated with decreased odds of suicidal ideation (AOR = 0.55, 95% CI: 0.31-0.99). These finding were independent of the effects of the presence of the suicidal ideation/attempts, comorbid mental disorders, social supports and chronic physical conditions at baseline. These results suggest that religious attendance is possibly an independent protective factor against suicide attempts.