Injectable and oral contraception and the incidence and progression of cervical disease in HIV-infected women in South Africa

Few data exist regarding the effect of hormonal contraception (HC) on incidence and progression of cervical disease (e.g., cervical dysplasia, squamous intraepithelial lesions, cervical intraepithelial neoplasia) in HIV-infected African women

Association between cervical dysplasia and human papillomavirus in HIV seropositive women from Johannesburg South Africa

ObjectiveTo examine the association between CD4 counts, HPV infection and the risk of cervical neoplasia among HIV-seropositive women.MethodsA cross-sectional observational study was conducted among 1,010 HIV-seropositive women using cytology-based Pap smears. HPV DNA testing using Linear Array genotyping assay (Roche) was carried out in a subset of 191 patients. Multivariable-adjusted prevalence ratios (mPR) and 95% confidence intervals (CIs) were estimated with log-binomial regression.ResultsAmong 1,010 HIV-seropositive women, the prevalence of AGC/ASCUS, LSIL and HSIL or greater was 8.3, 23.5 and 18.0%, respectively. The risk of cervical lesions was higher with CD4500/mm3. HPV types 16 (41.7%) and HPV 56 (22.2%) were the most common types in HSIL cases. Women with CD4 levels<200/mm3 had a higher prevalence of HPV types 16 (p<0.01) and 66 (p=0.04). No statistical relationship between cervical lesions and HAART use was found.ConclusionThe burden of HPV infection and HSIL was high and correlated with HIV-induced immunosuppression. HPV 16 was the most common type in HSIL and increased in prevalence with greater immune suppression. Prophylactic HPV 16 vaccination could prevent approximately 40% of HSIL cases. Strengthening screening programs is imperative in this population

Randomized Trial of Time-Limited Interruptions of Protease Inhibitor-Based Antiretroviral Therapy (ART) vs. Continuous Therapy for HIV-1 Infection

Background The clinical outcomes of short interruptions of PI-based ART regimens remains undefined. Methods A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load/ml and CD4 T cell count \u3e450 cells/µl on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count \u3e350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints. Results The proportions of CD4 counts \u3e350 cells/µl were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: −0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm. Conclusion We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur

Highly active antiretroviral therapy and cervical dysplasia in HIV-positive women in South Africa

BackgroundThe risk of squamous intra-epithelial lesions (SIL) is higher in HIV-positive women. As these women begin to live longer due to highly active antiretroviral therapy (HAART), their risk of cervical cancer may increase. Few data exist regarding the effect of HAART on the incidence and progression of SIL in HIV-positive African women. The aim of this study was to evaluate the effect of HAART on the incidence and progression of SIL in HIV-positive women in South Africa.MethodsA prospective observational study of HIV-seropositive women was conducted over 5 years in an HIV treatment clinic in Johannesburg, South Africa. The participants consisted of 601 women on and off HAART who had repeat Pap smears greater than 6 months apart. The effect of HAART use on incidence and progression rates of SIL was determined using multivariate Poisson regression to obtain incidence rate ratios (IRRs), adjusted for age, CD4 count and other potential confounders.ResultsMedian follow-up time was 445 days (inter-quartile range 383, 671). The crude rate of incidence of any SIL was 15.9 episodes (95% confidence limit (CL) 12.7, 19.9) per 100 person-years; the crude rate of all progression of cervical dysplasia among women was 13.5 episodes (95% CL 11.3, 16.1) per 100 person-years. HAART use was associated with a robust reduction in the rate of incidence and progression of cervical lesions, adjusted IRR=0.55 (95% CL 0.37, 0.80). Sensitivity analyses confirmed this main association held for incidence and progression when they were considered separately, and that the result was not dependent on the length of HAART exposure.ConclusionHAART use was associated with a reduction in the rate of both incidence and progression of cervical lesions among HIV-positive women

Association between HIV replication and serum leptin levels: an observational study of a cohort of HIV-1-infected South African women

<p>Abstract</p> <p>Background</p> <p>Advanced HIV infection can result in lipoatrophy and wasting, even in the absence of ongoing opportunistic infections, suggesting that HIV may directly affect adipose tissue amount and distribution.</p> <p>Methods</p> <p>We assessed the relationship of fat (measured using anthropometry, DEXA, MRI scans) or markers related to glucose and lipid metabolism with viral load in a cross-sectional sample of 83 antiretroviral-naïve HIV-1-infected South African women. A multivariable linear model was fitted to log₁₀VL to assess the combined effect of these variables.</p> <p>Results</p> <p>In addition to higher T cell activation, women with viral load greater than the population median had lower waist circumference, body mass index and subcutaneous abdominal fat, as well as lower serum leptin. We demonstrate that leptin serum levels are inversely associated with viral replication, independent of the amount of adipose tissue. This association is maintained after adjusting for multiple variables associated with disease progression (i.e., cellular activation and innate immunity effector levels).</p> <p>Conclusions</p> <p>Our results demonstrate that serum leptin levels are inversely associated with viral replication, independent of disease progression: we postulate that leptin may affect viral replication.</p

Mitochondria and Energetic Depression in Cell Pathophysiology

Mitochondrial dysfunction is a hallmark of almost all diseases. Acquired or inherited mutations of the mitochondrial genome DNA may give rise to mitochondrial diseases. Another class of disorders, in which mitochondrial impairments are initiated by extramitochondrial factors, includes neurodegenerative diseases and syndromes resulting from typical pathological processes, such as hypoxia/ischemia, inflammation, intoxications, and carcinogenesis. Both classes of diseases lead to cellular energetic depression (CED), which is characterized by decreased cytosolic phosphorylation potential that suppresses the cell’s ability to do work and control the intracellular Ca2+ homeostasis and its redox state. If progressing, CED leads to cell death, whose type is linked to the functional status of the mitochondria. In the case of limited deterioration, when some amounts of ATP can still be generated due to oxidative phosphorylation (OXPHOS), mitochondria launch the apoptotic cell death program by release of cytochrome c. Following pronounced CED, cytoplasmic ATP levels fall below the thresholds required for processing the ATP-dependent apoptotic cascade and the cell dies from necrosis. Both types of death can be grouped together as a mitochondrial cell death (MCD). However, there exist multiple adaptive reactions aimed at protecting cells against CED. In this context, a metabolic shift characterized by suppression of OXPHOS combined with activation of aerobic glycolysis as the main pathway for ATP synthesis (Warburg effect) is of central importance. Whereas this type of adaptation is sufficiently effective to avoid CED and to control the cellular redox state, thereby ensuring the cell survival, it also favors the avoidance of apoptotic cell death. This scenario may underlie uncontrolled cellular proliferation and growth, eventually resulting in carcinogenesis

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Challenges and Opportunities to the Flow of Communication: Online Focus Groups with Parents of Young Children, Professional Caregivers, and Intermediaries

Stehr P, Reifegerste D, Rossmann C, Lindemann A-K, Schulze A. Challenges and Opportunities to the Flow of Communication: Online Focus Groups with Parents of Young Children, Professional Caregivers, and Intermediaries. American Behavioral Scientist . 2023.To explore the information behavior in the context of child injury prevention, we conducted online focus groups with parents, professional caregivers, and intermediaries as part of a larger project. In this paper, we discuss our qualitative interview design: audiovisual, synchronous online focus groups. To do so, we analyze a crucial methodological issue of focus group interviews: the flow of communication. In our study, three main topics emerged that influenced the flow of communication in online focus groups: (a) communication mode(s), (b) (co-)moderation, and (c) distractions and interjections of other people. We conclude that depending on the research topic and target group, audio-only communication may be advantageous compared to audiovisual communication because lay people may disclose more on sensitive topics. Moreover, the considerate composition of the focus group is essential for participants' interaction, so that all participants feel they have an important part to contribute to the discussion. Skilled co-moderation is crucial to successfully integrating all participants and evolving communication threads, and dealing with disruptions

A Mobile Health Information Behavior Model: Theoretical Development and Mixed-Method Testing in the Context of Mobile Apps on Child Poisoning Prevention

Stehr P, Ermel L, Rossmann C, Reifegerste D, Lindemann A-K, Schulze A. A Mobile Health Information Behavior Model: Theoretical Development and Mixed-Method Testing in the Context of Mobile Apps on Child Poisoning Prevention. Journal of Health Communication. 2023: 2250313.While several studies have explored the use of mobile health applications, few have observed determinants of mobile health information behavior. To develop a model explaining parents' mobile information behavior on child poisoning prevention, we first explored relevant theories to suggest a theoretical model. In that, we combine existing models on risk and health information seeking, such as the Planned Risk Information Seeking Model, with models on the acceptance of mobile technologies, such as the Unified Theory of Acceptance and Use of Technologies. Thereafter, we employed a sequential mixed-method design with an initial qualitative study (four online focus groups with n = 25 parents in total) and a standardized online survey of n = 1,013 parents to evaluate our research model. Results confirm that both, determinants of information seeking and determinants of technology acceptance, contribute to the explanation of mobile information behavior. App use intention was mainly related to the performance expectancy of app use, the subjective information norm, and social influence on app use. To increase the usage of prevention apps and contribute to the reduction of child injuries, communication on poisoning apps should address subdimensions of the performance expectancy, such as their utility and peoples' trust in app providers. Moreover, physicians are important multipliers for these messages

Multiple perspectives in concepts for multipliers. Interpersonal communication measures using the example of child accident prevention

Reifegerste D, Stehr P, Ermel L, Rossmann C, Lindemann A-K, Schulze A. Multiperspektivität im Multiplikatorenansatz. Interpersonale Kommunikationsmaßnahmen am Beispiel der Kinderunfallprävention. Prävention und Gesundheitsförderung. 2022.Background Caregivers who supervise children under 7 years of age, such as (grand)parents or medical and pedagogical staff, are important target groups for communication measures in child accident prevention. To identify and reach them, multipliers from their ranks (peers and professionals) as well as multipliers from institutions (intermediaries or second order multipliers) can be important, each with their own preferences for information channels and communication occasions; however, existing information dissemination approaches do not sufficiently consider these multiple perspectives and the reciprocal perspectives of communication partners. Objective Based on a project on child accident prevention we therefore analyzed which interpersonal information sources and information occasions the respective subgroups consider significant in order to identify and reach appropriate multipliers. Material and methods For this purpose, a total of eight focus groups and four individual interviews were conducted with parents (n = 25), medical and pedagogical care personnel (n = 17), and intermediaries from institutions (n = 15). Results The results show that the perspectives of the different dialogue and multiplier groups on information sources used and occasions for seeking and sharing information differ significantly. Discussion These results underline the importance of examining the different perspectives as part of a multiplier concept and taking them into account in the development of communication measures. Future research should examine to what extent the results can be transferred to other prevention fields.Hintergrund Betreuungspersonen von Kindern unter 7 Jahren, etwa (Groß‑)Eltern oder medizinisches und pädagogisches Personal, sind wichtige Zielgruppen für Kommunikationsmaßnahmen in der Kinderunfallprävention. Um sie zu identifizieren und zu erreichen, können Multiplikatoren aus ihren Reihen (Peers und Professionals) oder Multiplikatoren von Institutionen (Intermediäre oder Multiplikatoren zweiter Ordnung) von Bedeutung sein, die jeweils eigene Präferenzen für Informationswege und Kommunikationsanlässe aufweisen. Allerdings berücksichtigen vorhandene Multiplikatorenansätze diese Multiperspektivität und die wechselseitigen Sichtweisen der Kommunikationspartner nur unzureichend. Zielstellung Anhand eines Projekts zur Kinderunfallprävention haben wir daher analysiert, welche interpersonalen Informationsquellen und Informationsanlässe die jeweiligen Teilgruppen als bedeutsam erachten, um entsprechende Multiplikatoren identifizieren und erreichen zu können. Material und Methoden Dafür wurden insgesamt 8 Fokusgruppen und 4 Einzelinterviews mit Eltern (n = 25), medizinischem und pädagogischem Betreuungspersonal (n = 17) und Intermediären von Institutionen (n = 15) durchgeführt. Ergebnisse Die Ergebnisse zeigen, dass sich die Perspektiven der verschiedenen Multiplikatorengruppen auf genutzte Informationsquellen und Anlässe zur Informationssuche und -weitergabe deutlich unterscheiden. Diskussion Ein Multiplikatorenkonzept sollte die verschiedenen Perspektiven erheben und für die Entwicklung der Kommunikationsmaßnahmen berücksichtigen. Es bleibt zu prüfen, inwieweit die Ergebnisse auf andere Präventionsfelder übertragbar sind