The Reporting Recommendations Intended for Pharmaceutical Risk Minimization Evaluation Studies: Standards for Reporting of Implementation Studies Extension (RIMES-SE)

IntroductionThe Reporting recommendations Intended for pharmaceutical risk Minimization Evaluation Studies (RIMES) was developed to improve the quality of reporting of risk minimization program evaluations. In light of continued inadequacies in study reporting, and high-profile program implementation failures, we updated the RIMES Checklist to incorporate additional concepts from the Standards for Reporting of Implementation studies (StaRI).MethodsThe development of the updated checklist, the RIMES-StaRI Extension (RIMES-SE), entailed developing a study protocol and drafting an initial pool of items based on a mapping of the RIMES against the StaRI checklist. A modified e-Delphi exercise was then conducted to determine the importance and understandability of items for checklist inclusion. An expert workshop and an online commentary period for additional feedback followed.ResultsThe RIMES-SE contains 27 items. It includes two signature features of the StaRI Checklist: 1) a dual strand of items (represented in two columns) describing the risk minimization program (the ‘intervention’) and the corresponding implementation strategy; and 2) applicable to an array of different research methodologies.ConclusionsThe RIMES-SE Statement and Checklist extends the reporting guidelines set forth in the original RIMES Checklist via inclusion of key implementation science concepts. It is intended to improve the quality and transparency of reporting of risk minimization evaluation studies so as to advance drug safety science.<br/

Telling partners about chlamydia: how acceptable are the new technologies?

BACKGROUND Partner notification is accepted as a vital component in the control of chlamydia. However, in reality, many sexual partners of individuals diagnosed with chlamydia are never informed of their risk. The newer technologies of email and SMS have been used as a means of improving partner notification rates. This study explored the use and acceptability of different partner notification methods to help inform the development of strategies and resources to increase the number of partners notified. METHODS Semi-structured telephone interviews were conducted with 40 people who were recently diagnosed with chlamydia from three sexual health centres and two general practices across three Australian jurisdictions. RESULTS Most participants chose to contact their partners either in person (56%) or by phone (44%). Only 17% chose email or SMS. Participants viewed face-to-face as the "gold standard" in partner notification because it demonstrated caring, respect and courage. Telephone contact, while considered insensitive by some, was often valued because it was quick, convenient and less confronting. Email was often seen as less personal while SMS was generally considered the least acceptable method for telling partners. There was also concern that emails and SMS could be misunderstood, not taken seriously or shown to others. Despite these, email and SMS were seen to be appropriate and useful in some circumstances. Letters, both from the patients or from their doctor, were viewed more favourably but were seldom used. CONCLUSION These findings suggest that many people diagnosed with chlamydia are reluctant to use the new technologies for partner notification, except in specific circumstances, and our efforts in developing partner notification resources may best be focused on giving patients the skills and confidence for personal interaction.The study was funded by the Australian Federal Government Department of Health and Ageing Chlamydia Pilot Program of Targeted Grants

Better than nothing? Patient-delivered partner therapy and partner notification for chlamydia: the views of Australian general practitioners

BACKGROUND Genital chlamydia is the most commonly notified sexually transmissible infection (STI) in Australia and worldwide and can have serious reproductive health outcomes. Partner notification, testing and treatment are important facets of chlamydia control. Traditional methods of partner notification are not reaching enough partners to effectively control transmission of chlamydia. Patient-delivered partner therapy (PDPT) has been shown to improve the treatment of sexual partners. In Australia, General Practitioners (GPs) are responsible for the bulk of chlamydia testing, diagnosis, treatment and follow up. This study aimed to determine the views and practices of Australian general practitioners (GPs) in relation to partner notification and PDPT for chlamydia and explored GPs' perceptions of their patients' barriers to notifying partners of a chlamydia diagnosis. METHODS In-depth, semi-structured telephone interviews were conducted with 40 general practitioners (GPs) from rural, regional and urban Australia from November 2006 to March 2007. Topics covered: GPs' current practice and views about partner notification, perceived barriers and useful supports, previous use of and views regarding PDPT.Transcripts were imported into NVivo7 and subjected to thematic analysis. Data saturation was reached after 32 interviews had been completed. RESULTS Perceived barriers to patients telling partners (patient referral) included: stigma; age and cultural background; casual or long-term relationship, ongoing relationship or not. Barriers to GPs undertaking partner notification (provider referral) included: lack of time and staff; lack of contact details; uncertainty about the legality of contacting partners and whether this constitutes breach of patient confidentiality; and feeling both personally uncomfortable and inadequately trained to contact someone who is not their patient. GPs were divided on the use of PDPT--many felt concerned that it is not best clinical practice but many also felt that it is better than nothing.GPs identified the following factors which they considered would facilitate partner notification: clear clinical guidelines; a legal framework around partner notification; a formal chlamydia screening program; financial incentives; education and practical support for health professionals, and raising awareness of chlamydia in the community, in particular amongst young people. CONCLUSIONS GPs reported some partners do not seek medical treatment even after they are notified of being a sexual contact of a patient with chlamydia. More routine use of PDPT may help address this issue however GPs in this study had negative attitudes to the use of PDPT. Appropriate guidelines and legislation may make the use of PDPT more acceptable to Australian GPs.The Australian Federal Government Department of Health and Ageing Chlamydia Pilot Program of Targeted Grants funded the study

Self-efficacy for coping with cancer in a multiethnic sample of breast cancer patients: Associations with barriers to pain management and distress

Objectives This study examined the interrelations of self-efficacy for coping with cancer, perceived barriers to pain management, distress, and pain outcomes in a multiethnic sample of breast cancer patients. The extent to which ethnicity (Black, Latina, or White), language (English or Spanish), and level of education and income predicted these variables was also assessed. Methods Participants were breast cancer patients with persistent pain (N=87) who were recruited from oncology clinics in New York City. Patients completed an assessment battery that included measures of self-efficacy for coping with cancer, barriers to pain management, distress, and pain outcomes. Results Greater self-efficacy for coping with cancer was associated with older age, less time since diagnosis, and less distress. In addition, less self-efficacy for seeking and understanding medical information, Spanish language preference, and greater distress predicted greater barriers to pain management. Average pain severity was higher among Spanish-speaking individuals and those with lower incomes. Discussion Findings point to the potential importance of self-efficacy for seeking and understanding medical information and perceived barriers to pain management in understanding the psychologic well-being of breast cancer patients with pain, especially those who are Spanish-speaking

Assessment of hydropyrolysis as a method for the quantification of black carbon using standard reference materials

A wide selection of thermal, chemical and optical methods have been proposed for the quantification of black carbon (BC) in environmental matrices, and the results to date differ markedly depending upon the method used. A new approach is hydropyrolysis (hypy), where pyrolysis assisted by high hydrogen pressures (150 bar) facilitates the complete reductive removal of labile organic matter, so isolating a highly stable portion of the BC continuum (defined as BChypy). Here, the potential of hypy for the isolation and quantification of BC is evaluated using the 12 reference materials from the International BC Ring Trial, comprising BC-rich samples, BC-containing environmental matrices and BC-free potentially interfering materials. By varying the hypy operating conditions, it is demonstrated that lignocellulosic, humic and other labile organic carbon material (defined as non-BChypy) is fully removed by 550 °C, with hydrogasification of the remaining BChypy not commencing until over 575 °C. The resulting plateau in sample mass and carbon loss is apparent in all of the environmental samples, facilitating BC quantification in a wide range of materials. The BChypy contents for all 12 ring trial samples fall within the range reported in the BC inter-comparison study, and systematic differences with other methods are rationalised. All methods for BC isolation, including hypy are limited by the fact that BC cannot be distinguished from extremely thermally mature organic matter; for example in high rank coals. However, the data reported here indicates that BChypy has an atomic H/C ratio of less than 0.5 and therefore comprises a chemically well-defined polyaromatic structure in terms of the average size of peri-condensed aromatic clusters of &gt;7 rings (24 carbon atoms), that is consistent across different sample matrices. This, together with the sound underlying rationale for the reductive removal of labile organic matter, makes hypy an ideal approach for matrix independent BC quantification. The hypy results are extremely reproducible, with BChypy determinations from triplicate analyses typically within ±2% across all samples, limited mainly by the precision of the elemental analyser

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes

The thesan project: public data release of radiation-hydrodynamic simulations matching reionization-era JWST observations

Cosmological simulations serve as invaluable tools for understanding the Universe. However, the technical complexity and substantial computational resources required to generate such simulations often limit their accessibility within the broader research community. Notable exceptions exist, but most are not suited for simultaneously studying the physics of galaxy formation and cosmic reionization during the first billion years of cosmic history. This is especially relevant now that a fleet of advanced observatories (e.g. James Webb Space Telescope, Nancy Grace Roman Space Telescope, SPHEREx, ELT, SKA) will soon provide an holistic picture of this defining epoch. To bridge this gap, we publicly release all simulation outputs and post-processing products generated within the THESAN simulation project at https://thesan-project.com. This project focuses on the $z \geq 5.5$ Universe, combining a radiation-hydrodynamics solver (AREPO-RT), a well-tested galaxy formation model (IllustrisTNG) and cosmic dust physics to provide a comprehensive view of the Epoch of Reionization. The THESAN suite includes 16 distinct simulations, each varying in volume, resolution, and underlying physical models. This paper outlines the unique features of these new simulations, the production and detailed format of the wide range of derived data products, and the process for data retrieval. Finally, as a case study, we compare our simulation data with a number of recent observations from the James Webb Space Telescope, affirming the accuracy and applicability of THESAN. The examples also serve as prototypes for how to utilise the released dataset to perform comparisons between predictions and observations.Comment: Data and documentation at https://www.thesan-project.com, comments and requests welcome, paper submitted to MNRA

HIV Infection and the Risk of World Health Organization-Defined Sudden Cardiac Death

Background People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear. Methods and Results This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant\u27s first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral load were associated with World Health Organization (WHO)–defined SCD risk. Among 144 336 participants (30% people living with HIV), the mean (SD) baseline age was 50.0 years (10.6 years), 97% were men, and 47% were of Black race. During follow‐up (median, 9.0 years), 3035 SCDs occurred. HIV infection was associated with increased SCD risk (hazard ratio [HR], 1.14; 95% CI, 1.04–1.25), adjusting for possible confounders. In analyses with time‐varying CD4 and HIV viral load, people living with HIV with CD4 counts \u3c 200 cells/mm3 (HR, 1.57; 95% CI, 1.28–1.92) or viral load \u3e 500 copies/mL (HR, 1.70; 95% CI, 1.46–1.98) had increased SCD risk versus veterans without HIV. In contrast, people living with HIV who had CD4 cell counts \u3e 500 cells/mm3 (HR, 1.03; 95% CI, 0.90–1.18) or HIV viral load \u3c 500 copies/mL (HR, 0.97; 95% CI, 0.87–1.09) were not at increased SCD risk. Conclusions HIV infection is associated with increased risk of WHO‐defined SCD among those with elevated HIV viral load or low CD4 cell counts

Management of Chlamydia Cases in Australia (MoCCA): protocol for a non-randomised implementation and feasibility trial

INTRODUCTION: The sexually transmitted infection chlamydia can cause significant complications, particularly among people with female reproductive organs. Optimal management includes timely and appropriate treatment, notifying and treating sexual partners, timely retesting for reinfection and detecting complications including pelvic inflammatory disease (PID). In Australia, mainstream primary care (general practice) is where most chlamydia infections are diagnosed, making it a key setting for optimising chlamydia management. High reinfection and low retesting rates suggest partner notification and retesting are not uniformly provided. The Management of Chlamydia Cases in Australia (MoCCA) study seeks to address gaps in chlamydia management in Australian general practice through implementing interventions shown to improve chlamydia management in specialist services. MoCCA will focus on improving retesting, partner management (including patient-delivered partner therapy) and PID diagnosis. METHODS AND ANALYSIS: MoCCA is a non-randomised implementation and feasibility trial aiming to determine how best to implement interventions to support general practice in delivering best practice chlamydia management. Our method is guided by the Consolidated Framework for Implementation Research and the Normalisation Process Theory. MoCCA interventions include a website, flow charts, fact sheets, mailed specimen kits and autofills to streamline chlamydia consultation documentation. We aim to recruit 20 general practices across three Australian states (Victoria, New South Wales, Queensland) through which we will implement the interventions over 12–18 months. Mixed methods involving qualitative and quantitative data collection and analyses (observation, interviews, surveys) from staff and patients will be undertaken to explore our intervention implementation, acceptability and uptake. Deidentified general practice and laboratory data will be used to measure pre-post chlamydia testing, retesting, reinfection and PID rates, and to estimate MoCCA intervention costs. Our findings will guide scale-up plans for Australian general practice. ETHICS AND DISSEMINATION: Ethics approval was obtained from The University of Melbourne Human Research Ethics Committee (Ethics ID: 22665). Findings will be disseminated via conference presentations, peer-reviewed publications and study reports