Efficient regulatory approval of two novel HIV prevention interventions in a resource-limited setting: experiences from Zimbabwe.

The global burden of HIV remains unacceptably high despite significant progress made in HIV treatment and prevention. There is an urgent need to scale up the comprehensive HIV prevention strategies that include pre-exposure prophylaxis (PrEP). Oral PrEP is highly effective in preventing HIV acquisition when taken regularly, but this remains a challenge for some at-risk individuals. Therefore, there is a need for other HIV prevention options. The dapivirine vaginal ring (DVR) and long-acting injectable cabotegravir (CAB-LA) are novel biomedical interventions that are safe and efficacious for HIV pre-exposure prophylaxis, as demonstrated in recently completed clinical trials. Timely roll-out and scalability of efficacious interventions depend on the registration process with the national medicine regulatory authorities (NMRAs). The Medicines Control Authority of Zimbabwe (MCAZ) was the first NMRA globally to approve the DVR in July 2021 and the first in Africa to approve CAB-LA for HIV prevention in July 2022. The regulatory review process for DVR and CAB-LA by MCAZ took 4.5 and 5.5 months, respectively. This efficient review process of the two interventions by MCAZ, a regulatory body in a resource-limited setting, provides important lessons to shorten timelines between the completion of the clinical development process and the registration of essential medicines.

Resistance-minimizing strategies for introducing a novel antibiotic for gonorrhea treatment: a mathematical modeling study.

Background: Gonorrhea is a highly prevalent sexually transmitted infection and an urgent public health concern due to increasing antibiotic resistance. Only ceftriaxone remains as the recommended treatment in the U.S. The prospect of approval of new anti-gonococcal antibiotics raises the question of how to deploy a new drug to maximize its clinically useful lifespan. Methods: We used a compartmental model of gonorrhea transmission in the U.S. population of men who have sex with men to compare strategies for introducing a new antibiotic for gonorrhea treatment. The strategies tested included holding the new antibiotic in reserve until the current therapy reached a threshold prevalence of resistance; using either drug, considering immediate and gradual introduction of the new drug; and combination therapy. The primary outcome of interest was the time until 5% prevalence of resistance to both the novel drug and to the current first-line drug (ceftriaxone). Findings: The reserve strategy was consistently inferior for mitigating antibiotic resistance under the parameter space explored. The reserve strategy was increasingly outperformed by the other strategies as the probability of de novo resistance emergence decreased and as the fitness costs associated with resistance increased. Combination therapy tended to prolong the development of antibiotic resistance and minimize the number of annual gonococcal infections. Interpretation: Our study argues for rapid introduction of new anti-gonococcal antibiotics, recognizing that the feasibility of each strategy must incorporate cost, safety, and other practical concerns. The analyses should be revisited once robust estimates of key parameters-likelihood of emergence of resistance and fitness costs of resistance for the new antibiotic-are available. Funding: U.S. Centers for Disease Control and Prevention (CDC), National Institute of Allergy and Infectious Diseases.

Lessons Learnt during COVID-19 Lockdown: A Qualitative Study of South African Families.

In a pandemic, such as COVID-19, with every single person struggling to deal with the unknown, it is often within the family that support is found but it is also within the family that circumstances, contexts and behaviours could further drive the pandemic and where they struggle to cope. This is novel research in the South African context with no known information regarding family life during and post the pandemic. This study, therefore, explores the lessons learnt during COVID-19 by South African families. A qualitative approach was employed to guide the gathering and analysis of the data. Data were collected from a sample of 31 family members above the age of 18 years from communities of the Western Cape Province and analysed through thematic analysis. According to the participants interviewed some of the significant lessons learnt from the lockdown include hygiene and health consciousness, appreciation for family, valuing life, self-introspection, less dependency, remote working, and financial savings. The realisation of such lessons even post-pandemic has the potential of strengthening families to be a resource of coping and resilience during very difficult times at the same time, contributing to greater physical, social, and economic functioning of families across South Africa.

State-level gonorrhea rates and expedited partner therapy laws: insights from time series analyses.

OBJECTIVE: In this study, we examined state-level monthly gonorrhea morbidity and assessed the potential impact of existing expedited partner therapy (EPT) laws in relation to the time that the laws were enacted. STUDY DESIGN: Longitudinal study. METHODS: We obtained state-level monthly gonorrhea morbidity (number of cases/100,000 for males, females and total) from the national surveillance data. We used visual examination (of morbidity trends) and an autoregressive time series model in a panel format with intervention (interrupted time series) analysis to assess the impact of state EPT laws based on the months in which the laws were enacted. RESULTS: For over 84% of the states with EPT laws, the monthly morbidity trends did not show any noticeable decreases on or after the laws were enacted. Although we found statistically significant decreases in gonorrhea morbidity within four of the states with EPT laws (Alaska, Illinois, Minnesota, and Vermont), there were no significant decreases when the decreases in the four states were compared contemporaneously with the decreases in states that do not have the laws. CONCLUSION: We found no impact (decrease in gonorrhea morbidity) attributable exclusively to the EPT law(s). However, these results do not imply that the EPT laws themselves were not effective (or failed to reduce gonorrhea morbidity), because the effectiveness of the EPT law is dependent on necessary intermediate events/outcomes, including sexually transmitted infection service providers' awareness and practice, as well as acceptance by patients and their partners.

Risk-based versus alternative algorithms for antibiotic prophylaxis among women seeking early suction abortion: a cost-effectiveness simulation.

BACKGROUND: Particularly in resource-poor settings, simple, inexpensive, and cost-effective algorithms are needed to direct antibiotic prophylaxis to prevent sequelae of infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and bacterial vaginosis-associated organisms among women undergoing abortion. GOAL: To assess the prevalence of and risk factors for infections among women seeking abortion in Bali, Indonesia, and to use these data in designing a cost-effective risk-based prophylaxis algorithm. STUDY DESIGN: A cross-sectional analysis and data-based simulation of risk-based and alternative prophylaxis algorithms were performed. RESULTS: The risk-based algorithm would have provided prophylaxis to 70% (95% CI, 53-83%) of women with cervical infection, 64% (95% CI, 54-74%) of those with bacterial vaginosis, and 57% (95% CI, 42-72%) of those with trichomoniasis. For cervical infection, the algorithm was more cost effective than all others evaluated. The cost-effectiveness was acceptable for bacterial vaginosis. CONCLUSIONS: Risk-based algorithms may be cost effective in identifying women likely to benefit from preabortion prophylaxis. Prospective evaluation is needed to validate these findings.

The increasing marginal benefit of condom usage.

PURPOSE: Condom use is promoted as a primary strategy for preventing sexual transmission of human immunodeficiency virus (HIV). This paper analyzes how incremental changes in condom compliance rates can affect an individual's risk of acquiring HIV. METHODS: We developed a simple mathematical model of HIV transmission in which the cumulative probability of HIV infection depended in part upon the percentage of acts in which a condom was used. We applied basic methods of calculus to differentiate the mathematical model with respect to the probability of condom usage. We applied values from published studies to the model to illustrate how the marginal benefits of condom usage vary across different populations. RESULTS: In general, the marginal benefit of condom usage increases as condom compliance increases. CONCLUSIONS: The marginal benefits of increased condom usage vary across different risk groups and across different levels of condom compliance. These results offer insight into the motivation behind the decision of whether or not to use condoms, and indicate possible ways to optimize the use of resources devoted to increasing condom usage by at-risk populations.

The rapid test paradox: when fewer cases detected lead to more cases treated: a decision analysis of tests for Chlamydia trachomatis.

BACKGROUND AND OBJECTIVES: Screening tests for detection of Chlamydia trachomatis include those processed in laboratories and those designed to be processed at the point of care. The latter tests can yield results at the time of the initial patient visit, but most available lab-processed tests have greater sensitivity. In settings where a proportion of patients do not return for treatment after positive test results, the less sensitive rapid tests could lead to the treatment of more patients and be more cost-effective. GOAL OF THIS STUDY: To determine the situations, if any, in which a rapid test might be more cost-effective and treat more infections than lab-based tests. STUDY DESIGN: A decision analysis framework was used to compare one point-of-care test (the BioStar Chlamydia OIA) with two lab-based tests (cell culture and the polymerase chain reaction [PCR] assay). It was assumed that all women in the model would be screened. Variables included in the analysis were the prevalence, test sensitivity and specificity, the probability of developing pelvic inflammatory disease after treated and untreated chlamydial infections, and the likelihood that patients would wait for rapid test results or return to the facility for treatment. RESULTS: The rapid test treated more cases of infection than the PCR alone if the return rate was less than 65%. A two-test algorithm of the rapid test followed by a PCR test on those initially testing negative identified and treated the greatest number of chlamydial infections and was the most cost-effective at all prevalences above 9%, but this finding was sensitive to the cost estimate for pelvic inflammatory disease. CONCLUSION: In settings where patient return for treatment is a problem, point-of-care tests contribute significantly to the detection and treatment of chlamydial infections among women.

Medication refusal and judicial activism: a reexamination of the effects of the Rivers decision.

OBJECTIVE: In 1986 New York State courts in Rivers v. Katz mandated judicial review of cases in which involuntarily hospitalized psychiatric patients formally refuse medications; previously only a clinical-administrative review was required. In an earlier study the authors found that formal refusals of medications declined significantly in the year after the Rivers decision and that length of time between refusal and its resolution increased. To determine whether these effects were maintained over time, data for the second year after the Rivers decision were examined. METHODS: Chi square analysis and analysis of variance were used to compare data from both a private and a state-operated hospital for the year before the Rivers decision with data from the first and second years after. RESULTS: The significant declines in the number of patients formally refusing medications were maintained in the second year after Rivers at both hospitals, as were the significant increases in the length of time to resolution. In the second year, judges continued to uphold the treating psychiatrists' recommendations. The decline in the refusal rates was not found to be part of a broader trend that had been manifest before the Rivers decision. CONCLUSIONS: The sharp decline in refusals resulted in fewer patients having their medications reviewed by others not directly involved in their care. Increased time to resolution has diminished quality of care and has resulted in increased patient decompensation and staff injuries.

Predictors of two-year outcome among psychiatric outpatients.

This study hypothesized that social competence and clinical factors previously associated with psychiatric outcome among inpatients would be effective predictors of outcome among outpatients (N = 77) as well. Intake and 2-year outcome status were assessed multidimensionally with absolute-level and residualized indices of functioning, overall clinical status, and symptomatology. Menninger health-sickness proved to be the best single predictor, although Phillips premorbid functioning, Strauss-Carpenter prognosis, social class, and diagnostic severity also predicted well to outcome. Patterns of associated predictor/outcome variable clusters were described. Results suggest that a general social competence factor predicts to psychiatric outcome across the entire range of disorders, but that life events stress does not.

Predictors of outcome among adult psychiatric first-admissions.

This study comparatively evaluated the prognostic potential of 10 demographic and clinical factors previously associated with psychiatric outcome. The longitudinal design employed intensive, structured, reliable interview techniques. One hundred forty-five subjects from a representative sample (N = 217) of community mental health catchment area first lifetime admissions were assessed at hospitalization and at 2-year follow-up. Predictors examined included premorbid functioning, overall health-sickness, diagnostic severity, social class, sex, age, IQ, race, and life events. Outcome was assessed multidimensionally with absolute-level and residualized indices of functioning and symptomatology. Phillips Premorbid Status and social class emerged from correlation and multiple regression analyses as the best predictors of functioning level and overall clinical status, while IQ was the most prominent indicator of symptomatology changes. Results support the notion that a general social competence factor predicts to psychiatric outcome across the entire spectrum of severe disorders.

Right to refuse treatment: impact of Rivers v. Katz.

This article examines the impact of the New York court decision, Rivers v. Katz, which in June 1986 dramatically changed the state procedure for responding to involuntarily committed psychiatric patients who formally refused psychopharmacologic treatment. The court rejected the medically administered review process that had been used to respond to involuntarily committed psychiatric patients who formally refused medication, and replaced it with a judicial determination of competent and "substituted judgment" provided by the court. Post-Rivers, the rate of patients consistently refusing treatment decreased, and the time from refusal to resolution increased. The clinical, legal, and economic implications of the Rivers procedure are discussed.

Psychiatric service utilization differences by sex and locale.

Underutilization of psychiatric services by men relative to women may reflect discrepancies between the male sex role in Western societies and the patient role. We hypothesize that this will be more important in a rural than a nonrural setting for two reasons. First, the relative lack of anonymity in a rural setting makes more evident incongruities between sex role conventions and actual behaviour. Second, because of the increased cultural heterogeneity of urban areas, traditional sex roles are less clearly delineated. These considerations suggest that the ratio of males to females receiving treatment in a rural setting should be lower than in a nonrural setting. It was found that for treated incidence the ratio of males to females was significantly lower in a rural than in a non-rural setting (p less than .01); for treated prevalence a lower male to female ratio was found in the rural than the nonrural setting, although this did not achieve statistical significance.

Life events and psychopathology severity: comparisons between psychiatric outpatients and inpatients.

Relationships between life events stress variables and seven indices of psychopathology severity for a group of 97 never-hospitalized outpatients were compared with those of a previously studied group of 217 first-admission functional disorder psychiatric inpatients from the same geographical catchment areas. The hypotheses tested were that degree of life events stress would be correlated positively with indices of psychopathological severity and that the magnitudes of association would be higher for the outpatients. Bivariate correlations and stepwise multiple regression with other potential demographic and prognostic moderator variables provided evidence for significant, but somewhat differing, patterns in outpatient vs. inpatient stress/pathology relationships. Contrary to prediction, the magnitudes of significant and near-significant associations between life events and pathology severity were not different in the two samples.

IQ as a prognostic indicator in adult psychiatric first-admissions.

This study used IQ, along with measures of premorbid adjustment, health-sickness, symptom level, diagnostic severity and demographic data, to predict to 2-year outcome measures of level of functioning, health-sickness, and symptoms for a sample of 145 adult psychiatric first-admissions. It was hypothesized that IQ as an indicator of cognitive ability, or of general ability to adapt, would predict positively to improvement over the 2-year period. Data analysis was conducted with bivariate correlations and multiple regressions, using both absolute-level and residualized outcome variables. IQ showed modest, significant relationships with all absolute outcome indices and six of seven residualized measures, especially for a subsample of those with non-average IQ scores. Regressions showed that IQ provided independent prediction of symptom outcomes.

Social class and psychiatric disorder. The examination of an extreme.

Relationships between social status and various aspects of mental disorder have been of long-standing interest to both clinicians and researchers, and a large body of literature exists attesting to the importance of social status in understanding psychiatric illness and disability. Reports examining social status and schizophrenia suggest that relationships between socioeconomic status and psychiatric illness may rest heavily upon differences between the lowest socioeconomic stratum and the remainder of society. To investigate the extent to which relationships between socioeconomic status and psychiatric illness and disability reflect differences between a deviant lowest socioeconomic stratum and the remainder of society, data from 217 patients hospitalized for psychiatric disorder and reassessed at a 2-year follow-up were examined. At initial assessment, 17 patient characteristics were found to be associated with socioeconomic status; for seven of these 17 characteristics, the largest difference between classes was found between the lowest and the adjacent (next-lowest) social class. At follow-up, for five of 15 characteristics found to be related to social class, the greatest interclass difference occurred between the lowest and the adjacent social class. Both initially and at follow-up, significant associations between patient characteristics and social class remained when the lowest social class patients were excluded from the analyses.

On the expression of psychosis in different cultures: schizophrenia in an Indian and in a Nigerian community.

This sub-study of the WHO Determinants of Outcome of Severe Mental Disorders research project was aimed at characterizing the behavioral and expressive qualities of schizophrenia in two highly diverse cultures. Early research has indicated that the core elements involving affect, perceptual and cognitive dysfunction in schizophrenia are highly similar in form in most cultures of the world. Much of the cross-cultural literature emphasizes, however, strong differences in the ways in which schizophrenia is actually expressed and manifested in different settings. The basic methodology for psychiatric description and diagnosis in the WHO program was the Present State Examination. In five of the field centers a method for investigating the expressive quality and the social behavior of patients in their own communities through the eyes of significant others was applied. This method was then subjected to psychometric tests of cross-cultural applicability and found to be valid for comparing behavior across settings. The expressive patterns of the Indian and Nigerian patients were studied from two perspectives. Indian schizophrenics were described by family members as manifesting a more affective and "self-centered" orientation; the Nigerian patients presented with a highly suspicious, bizarre, anxious quality to the basic behavioral pattern. The main features of pathology were in general accord with the descriptions of indigenous psychiatrists. The special qualities of the psychosis in the two cultures were interpreted against the background of traditional psychopathological and anthropologic theories concerning the psychodynamics and the influence of differing social conflictual themes in the two cultures. Analysis of psychopathology in this manner was found to enhance understanding of underlying mechanisms and the role of cultural conflicts in its expression.

The prediction of relapse of schizophrenic patients using emotional data obtained from their relatives.

The capacity of anxiety and hostility outward scores derived from the content analysis of 5-minute speech samples from the relatives of patients to predict relapse or nonrelapse was tested in three distinct groups of schizophrenic patients. Significantly correct predictions were made which compared favorably to the predictive capacity of ratings obtained by means of the Camberwell Family Interview. The latter requires 1 to 2 hours to administer and about 1 hour to score, whereas the former method requires a tape-recorded 5-minute speech sample and up to 0.5 hour to score.