An Assessment of HIV/AIDS Risk in Higher Education Students in Yerevan, Armenia

Armenia\u27s current sociopolitical and economic instability and the alarming HIV incidence rates in neighboring countries amplify its risk for a national epidemic. The goals of this study were to assess HIV/AIDS knowledge and risk behaviors among higher education students in Yerevan. Knowledge of HIV transmission through sexual intercourse was markedly higher than that on intravenous transmission and prevailing myths; however, HIV/AIDS knowledge was not related to risk behaviors. Tobacco and alcohol prevalence was relatively high. Students reported risky sexual behaviors, including inconsistent condom use, casual sex, and multiple partners. In addition to descriptive statistics delineating gender differences across the target behavioral domains, bivariate and multivariate statistical analyses were used to understand factors that contributed to increased risk, including early age of initiation and the relationship between substance use and risky sexual activity. The study results provide much-needed information for the development of school- and community-based AIDS prevention programs in Armenia

Condoms and developmental contexts in younger adolescent boys

BACKGROUND: Condom use is a key part of sexually transmitted infection (STI) prevention for young men. Yet little is known about how younger adolescent boys initially learn about and use condoms. We examined sources of information, attitudes towards, acquisition, practice and early use of condoms among 14-16-year-old boys. METHODS: Thirty 14-16-year-old boys were recruited from a teen clinic serving a community with high STI rates and were asked open-ended questions about condoms, such as, "Where did you learn about condoms?" and "In what situations would you/would you not, use condoms." Interviews were audio recorded, transcribed and coded. Qualitative analysis focused upon key concepts and shared social cognitions related to condom use. RESULTS: Both sexually inexperienced and experienced participants perceived that sex feels or would feel less pleasurable with condoms. For almost all participants, families were the primary source of both information about condoms and of condoms themselves. This information focused on pregnancy prevention, with STIs secondary. Participants' views of condoms fell into three developmental groups: not interested in condoms and equating their use with interest in sex; exploring condoms out of either curiosity or in preparation for sex; and experienced with condom use. Exploring included behaviours such as checking condoms out and trying them on. CONCLUSIONS: Our findings of existing negative perceptions of condoms, the importance of families in learning about condoms and the developmental need to test and try on condoms before use have implications for adolescent STI prevention programmes

Risk of Late Mortality and Second Malignant Neoplasms among 5-Year Survivors of Young Adult Cancer: A Report of the Childhood, Adolescent, and Young Adult Cancer Survivors Research Program

We conducted a population-based retrospective study to assess the long-term risks of overall and cause-specific mortality and second malignant neoplasm (SMN) among survivors of young adult cancer compared to the risk in British Columbia (BC) population and to evaluate the effects of demographic and clinical factors on risk. 1248 5-year survivors of young adult cancer diagnosed 1970–1995 between 20 and 24 years of age were identified from the BC Cancer Registry and followed to the end of 2007. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated. The Cox proportional hazards model was used to estimate the effects of different demographic and disease-related characteristics on the risk of death and SMN. A total of 138 deaths and 62 SMNs were observed during follow-up. The overall SMR was 5.9 (95% CI 4.9–6.9) and the absolute excess risk was 5.3 per 1,000 person-years. The overall SIR was 3.0 (95% CI 2.3–3.8). Treatment with radiation resulted in increased risks of death and SMN. These observed increased risks emphasize the importance of prevention, surveillance, and treatment of late effects in survivors of young adult cancers

Conceptualisations of children’s wellbeing at school: the contribution of recognition theory

A large study in Australian schools aimed to elucidate understandings of ‘wellbeing’ and of factors in school life that contribute to it. Students and teachers understood wellbeing primarily, and holistically, in terms of interpersonal relationships, in contrast to policy documents which mainly focused on ‘problem areas’ such as mental health. The study also drew on recognition theory as developed by the social philosopher Axel Honneth. Results indicate that recognition theory may be useful in understanding wellbeing in schools, and that empirical research in schools may give rise to further questions regarding theory

Lessons Learned: It Takes a Village to Understand Inter-Sectoral Care Using Administrative Data across Jurisdictions

Cancer care is complex and exists within the broader healthcare system. The CanIMPACT team sought to enhance primary cancer care capacity and improve integration between primary and cancer specialist care, focusing on breast cancer. In Canada, all medically-necessary healthcare is publicly funded but overseen at the provincial/territorial level. The CanIMPACT Administrative Health Data Group’s (AHDG) role was to describe inter-sectoral care across five Canadian provinces: British Columbia, Alberta, Manitoba, Ontario and Nova Scotia. This paper describes the process used and challenges faced in creating four parallel administrative health datasets. We present the content of those datasets and population characteristics. We provide guidance for future research based on ‘lessons learned’. The AHDG conducted population-based comparisons of care for breast cancer patients diagnosed from 2007-2011. We created parallel provincial datasets using knowledge from data inventories, our previous work, and ongoing bi-weekly conference calls. Common dataset creation plans (DCPs) ensured data comparability and documentation of data differences. In general, the process had to be flexible and iterative as our understanding of the data and needs of the broader team evolved. Inter-sectoral data inconsistencies that we had to address occurred due to differences in: 1) healthcare systems, 2) data sources, 3) data elements and 4) variable definitions. Our parallel provincial datasets describe the breast cancer diagnostic, treatment and survivorship phases and address ten research objectives. Breast cancer patient demographics reflect inter-provincial general population differences. Across provinces, disease characteristics are similar but underlying health status and use of healthcare services differ. Describing healthcare across Canadian jurisdictions assesses whether our provincial healthcare systems are delivering similar high quality, timely, accessible care to all of our citizens. We have provided a description of our experience in trying to achieve this goal and include a list of ‘lessons learned’ and a study process checklist for future use

Use of Elamipretide in patients assigned treatment in the compassionate use program : Case series in pediatric patients with rare orphan diseases

Funding Information: The authors wish to thank the patients and their families for participating, as well as Bret Fulton, RPh, and Jim Shiffer, RPh, Write On Time Medical Communications, LLC, for their writing and editorial assistance during the development of this manuscript. Mary Kay Koenig wishes to thank her research nurse, Lindsey Miller, for providing patient support and assisting with administration and education responsibilities. Publisher Copyright: © 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. © 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. © 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.Several mitochondrial diseases are caused by pathogenic variants that impair membrane phospholipid remodeling, with no FDA-approved therapies. Elamipretide targets the inner mitochondrial membrane where it binds to cardiolipin, resulting in improved membrane stability, cellular respiration, and ATP production. In clinical trials, elamipretide produced clinical and functional improvements in adults and adolescents with mitochondrial disorders, such as primary mitochondrial myopathy and Barth syndrome; however, experience in younger patients is limited and to our knowledge, these are the first case reports on the safety and efficacy of elamipretide treatment in children under 12 years of age. We describe the use of elamipretide in patients with mitochondrial disorders to provide dosing parameters in patients aged <12 years.Peer reviewe

The Intracranial Distribution of Gliomas in Relation to Exposure From Mobile Phones: Analyses From the INTERPHONE Study

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially influenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use

Design and methods for a randomized clinical trial comparing three outreach efforts to improve screening mammography adherence

<p>Abstract</p> <p>Background</p> <p>Despite the demonstrated need to increase screening mammography utilization and strong evidence that mail and telephone outreach to women can increase screening, most managed care organizations have not adopted comprehensive outreach programs. The uncertainty about optimum strategies and cost effectiveness have retarded widespread acceptance. While 70% of women report getting a mammogram within the prior 2 years, repeat mammography rates are less than 50%. This 5-year study is conducted though a Central Massachusetts healthcare plan and affiliated clinic. All womenhave adequate health insurance to cover the test.</p> <p>Methods/Design</p> <p>This randomized study compares 3 arms: reminder letter alone; reminder letter plus reminder call; reminder letter plus a second reminder and booklet plus a counselor call. All calls provide women with the opportunity to schedule a mammogram in a reasonable time. The invention period will span 4 years and include repeat attempts. The counselor arm is designed to educate, motivate and counsel women in an effort to alleviate PCP burden.</p> <p>All women who have been in the healthcare plan for 24 months and who have a current primary care provider (PCP) and who are aged 51-84 are randomized to 1 of 3 arms. Interventions are limited to women who become ≥18 months from a prior mammogram. Women and their physicians may opt out of the intervention study.</p> <p>Measurement of completed mammograms will use plan billing records and clinic electronic records. The primary outcome is the proportion of women continuously enrolled for ≥24 months who have had ≥1 mammogram in the last 24 months. Secondary outcomes include the number of women who need repeat interventions. The cost effectiveness analysis will measure all costs from the provider perspective.</p> <p>Discussion</p> <p>So far, 18,509 women aged 51-84 have been enrolled into our tracking database and were randomized into one of three arms. At baseline, 5,223 women were eligible for an intervention. We anticipate that the outcome will provide firm data about the maximal effectiveness as well as the cost effectiveness of the interventions both for increasing the mammography rate and the repeat mammography rate.</p> <p>Trial registration</p> <p><url>http://clinicaltrials.gov/</url><a href="http://www.clinicaltrials.gov/ct2/show/NCT01332032">NCT01332032</a></p

Use of Epivolve phage display to generate a monoclonal antibody with opsonic activity directed against a subdominant epitope on extracellular loop 4 of Treponema pallidum BamA (TP0326)

IntroductionSyphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum (Tp), is resurging globally. Tp’s repertoire of outer membrane proteins (OMPs) includes BamA (β-barrel assembly machinery subunit A/TP0326), a bipartite protein consisting of a 16-stranded β-barrel with nine extracellular loops (ECLs) and five periplasmic POTRA (polypeptide transport-associated) domains. BamA ECL4 antisera promotes internalization of Tp by rabbit peritoneal macrophages.MethodsThree overlapping BamA ECL4 peptides and a two-stage, phage display strategy, termed “Epivolve” (for epitope evolution) were employed to generate single-chain variable fragments (scFvs). Additionally, antisera generated by immunizing mice and rabbits with BamA ECL4 displayed by a Pyrococcus furiosus thioredoxin scaffold (PfTrxBamA/ECL4). MAbs and antisera reactivities were evaluated by immunoblotting and ELISA. A comparison of murine and rabbit opsonophagocytosis assays was conducted to evaluate the functional ability of the Abs (e.g., opsonization) and validate the mouse assay. Sera from Tp-infected mice (MSS) and rabbits (IRS) were evaluated for ECL4-specific Abs using PfTrxBamA/ECL4 and overlapping ECL4 peptides in immunoblotting and ELISA assays.ResultsEach of the five mAbs demonstrated reactivity by immunoblotting and ELISA to nanogram amounts of PfTrxBamA/ECL4. One mAb, containing a unique amino acid sequence in both the light and heavy chains, showed activity in the murine opsonophagocytosis assay. Mice and rabbits hyperimmunized with PfTrxBamA/ECL4 produced opsonic antisera that strongly recognized the ECL presented in a heterologous scaffold and overlapping ECL4 peptides, including S2. In contrast, Abs generated during Tp infection of mice and rabbits poorly recognized the peptides, indicating that S2 contains a subdominant epitope.DiscussionEpivolve produced mAbs target subdominant opsonic epitopes in BamA ECL4, a top syphilis vaccine candidate. The murine opsonophagocytosis assay can serve as an alternative model to investigate the opsonic potential of vaccinogens. Detailed characterization of BamA ECL4-specific Abs provided a means to dissect Ab responses elicited by Tp infection

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health