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Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy: a population-based cohort study

Por: Best · C. S. · Matheson · C. · Robertson · J. · Ritchie · T. · Cowden · F. · Dumbrell · J. · Duncan · C. · Kessavalou · K. · Woolston · C. · Schofield · J.
Objective

To investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone.

Design

Population-based cohort study.

Setting

Scotland, UK.

Participants

Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above.

Main outcome measures

All-cause mortality, drug-related deaths and non-drug related deaths.

Secondary outcome

ORT continuous treatment duration.

Analysis

Cox regression with time-varying covariates.

Results

During follow-up, 5776 of 46 899 participants died: 1398 while on coprescription and 4378 while on ORT only. The mortality per 100 person years was 3.11 during coprescription and 2.34 on ORT only. The adjusted HR for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted HR for drug-related death was 1.14 (95% CI, 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI, 1.09 to 1.30).

Conclusion

Coprescription of BZDs in ORT was associated with an increased risk of all-cause mortality, although with a small effect size than the international literature. Coprescribing was also associated with longer retention in treatment. Risk from BZD coprescription needs to be balanced against the risk from illicit BZDs and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide a clear clinical direction.

Trial registration number

NCT04622995.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions

Por: Wilkinson · J. · Heal · C. · Antoniou · G. A. · Flemyng · E. · Alfirevic · Z. · Avenell · A. · Barbour · G. · Brown · N. J. L. · Carlisle · J. · Clarke · M. · Dicker · P. · Dumville · J. C. · Grey · A. · Grohmann · S. · Gurrin · L. · Hayden · J. A. · Heathers · J. · Hunter · K. E. · Lasser
Introduction

Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions.

Methods and analysis

The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare.

Ethics and dissemination

The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

A Digitally Enabled, Pharmacist service to detecT medicine harms in residential aged care (nursing home) (ADEPT): protocol for a feasibility study

Por: Boord · M. S. · Brown · P. · Soriano · J. · Meola · T. · Dumuid · D. · Milte · R. · Roughead · E. E. · Lovell · N. H. · Stone · H. · Whitehouse · J. · Janetzki · J. L. · Gebreyohannes · E. A. · Lim · R.
Introduction

This feasibility study aims to develop and test a new model of practice in Australia using digital technologies to enable pharmacists to monitor early signs and symptoms of medicine-induced harms in residential aged care.

Methods and analysis

Thirty residents will be recruited from an aged care facility in South Australia. The study will be conducted in two phases. In phase I, the study team will work with aged care software providers and developers of digital technologies (a wearable activity tracker and a sleep tracking sensor) to gather physical activity and sleep data, as well as medication and clinical data from the electronic medication management system and aged care clinical software. Data will be centralised into a cloud-based monitoring platform (TeleClinical Care (TCC)). The TCC will be used to create dashboards that will include longitudinal visualisations of changes in residents’ health, function and medicine use over time. In phase II, the on-site pharmacist will use the centralised TCC platform to monitor each resident’s medicine, clinical, physical activity and sleep data to identify signs of medicine-induced harms over a 12-week period.

A mixed methods process evaluation applying the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) evaluation framework will be used to assess the feasibility of the service. Outcome measures include service reach, changes in resident symptom scores (measured using the Edmonton Symptom Assessment System), number of medication adverse events detected, changes in physical activity and sleep, number of pharmacist recommendations provided, cost analysis and proportion of all pharmacists’ recommendations implemented at 4-week, 8-week and 12-week postbaseline period.

Ethics and dissemination

Ethical approval has been obtained from the University of South Australia’s Human Research Ethics Committee (205098). Findings will be disseminated through published manuscripts, conference presentations and reporting to the study funder.

Trial registration number

ACTRN12623000506695.

Adherencia al tratamiento antirretroviral en pacientes adultos con VIH-SIDA: un artículo de revisión

Introducción. El objetivo de la siguiente revisión fue caracterizar la adherencia al tratamiento antirretroviral en pacientes adultos con VIH-SIDA en las dimensiones de grado de adherencia y factores de riesgo. Metodología. La presente revisión de la evidencia se llevó a cabo utilizando varios estudios que se hubieran publicado en los últimos 10 años en cualquier país a nivel mundial; la búsqueda de información se hizo en las bases de datos SciELO, PubMed, LILACS y Dialnet. Resultados. Se identificaron un total de 227 artículos; de los cuales, se excluyeron 211 publicaciones por no cumplir con los criterios de elegibilidad y finalmente los estudios que se incluyeron en esta investigación, fueron 14. Discusión. La falta de adherencia al tratamiento antirretroviral es un problema latente que se puso de manifiesto en la evidencia científica analizada y a partir de los diferentes estudios que fueron recabados, se encontró que más de la mitad de los pacientes si fueron adherentes; mientras que en otros, ocurrió totalmente lo contrario y en relación a los factores de riesgo asociados a la falta de adherencia, se identificaron los siguientes: factores relacionados con el régimen terapéutico (aparición de reacciones adversas; presencia de comorbilidades; mayor tiempo bajo tratamiento), relacionados con el individuo (estrés, depresión, estigma, olvido, consumo de sustancias psicoactivas y alcohol, grado académico, sexo masculino y menor edad) y relacionados con la situación social (falta de apoyo social familiar).

ABSTRACT

Introduction. The objective of the following review was to characterize adherence to antiretroviral treatment in adult patients with HIV-AIDS, in the dimensions of degree of adherence and risk factors. Methodology. This evidence review was carried out using several studies that have been published in the last 10 years in any country worldwide; the information search was carried out in the SciELO, PubMed, LILACS and Dialnet databases. Results. A total of 227 articles were identified; of which, 211 publications were excluded for not meeting the eligibility criteria and finally the studies that were included in this research were 14. Discussion. Lack of adherence to antiretroviral treatment is a latent problem that was highlighted in the scientific evidence analysed and from the different studies that were collected, it was found that more than half of the patients were adherent; while in others, the complete opposite occurred and in relation to the risk factors associated with non-adherence, the following were identified: factors related to the therapeutic regimen (occurrence of adverse reactions; presence of comorbidities; longer time under treatment), factors related to the individual (stress, depression, stigma, forgetfulness, consumption of psychoactive substances and alcohol, academic grade, male sex and younger age) and factors related to the social situation (lack of family social support).

Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression

by Karim S. Ladha, Jiwon Lee, Gabriella F. Mattina, Janneth Pazmino-Canizares, Duminda N. Wijeysundera, Fatemeh Gholamali Nezhad, Kaylyssa Philip, Vanessa K. Tassone, Fathima Adamsahib, Venkat Bhat, on behalf of the SMILE Study Investigators

Background

Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam.

Methods

In this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score Discussion

This pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression.

Trial registration

ClinicalTrials.gov NCT04957368. Registered on July 12, 2021.

Addressing patients’ unmet needs related to multidrug-resistant tuberculosis (MDR-TB) care: A qualitative research study from Pune city, India

by Sachin Atre, Jayshri Jagtap, Mujtaba Faqih, Yogita Dumbare, Trupti Sawant, Sunil Ambike, Maha Farhat

Aim

We aimed to identify and describe the unmet needs of patients with multidrug-resistant tuberculosis (MDR-TB).

Methods

As a part of larger cross-sectional mixed-methods (qualitative and quantitative data) study on pathways to MDR-TB care, here we present the qualitative component. We interviewed 128 (56 men and 72 women) individuals who had MDR-TB, aged > = 15 years, registered and treated under the National TB Elimination Program (NTEP) in Pune city of India. We carried out thematic analysis of participants’ narratives.

Results

We found that delays in diagnosis, lack of counseling, late referral to the NTEP and unwarranted expenditure were the main barriers to care that study participants experienced in the private sector. Provider dismissal of symptoms, non-courteous behavior, lack of hygiene in the referral centers, forced stay with other patients and lack of support for psychological/psychiatric problems were identified as a few additional challenges that participants faced at the NTEP care centers.

Conclusion

Using qualitative data from experiences of participants with MDR-TB, we identify patients’ several unmet needs, attention to which can improve MDR-TB care. Educating private providers about MDR-TB risk and available rapid molecular assays can help the timely diagnosis of MDR-TB and reduce patients’ out of pocket costs. At the RNTCP/NTEP, measures such as training health workers to build rapport with patients, maintaining hygienic environments in the health centers with adequate isolation of participants with MDR from other serious cases, referral of patients with psychiatric symptoms to mental health specialists and monitoring drug shortages can help in improving care delivery.

Trajectories of self-kindness, common humanity, and mindfulness during the COVID-19 pandemic: A person-oriented multi-trajectory approach

by Robin Wollast, Éric Lacourse, Geneviève A. Mageau, Mathieu Pelletier-Dumas, Anna Dorfman, Véronique Dupéré, Jean-Marc Lina, Dietlind Stolle, Roxane de la Sablonnière

The COVID-19 pandemic has produced unprecedented changes in the lives of many people. Although research has documented associations between concerns related to COVID-19 and poor mental health indicators, fewer studies have focused on positive factors that could help people better cope with this stressful social context. To fill this gap, the present research investigated the trajectories of self-compassion facets in times of dramatic social change. Using a longitudinal research design, we described the trajectories of self-kindness, common humanity, and mindfulness during the first eight months of the COVID-19 pandemic, in a representative sample of Canadian adults (N = 3617). Relying on a multi-trajectory group-based approach, we identified clusters of individuals following persistently low (4.0%), moderate-low (39.3%), moderate-high (46.7%), and high (10.0%) levels of self-kindness, common humanity, and mindfulness. Interestingly, we found that compassionate self-responding trajectories were mainly stable over time with minor fluctuations for some groups of individuals, in line with the epidemiological situation. In terms of covariates, we observed that older women were more likely to follow trajectories of high compassionate self-responding, as compared to the other age and gender groups. In terms of mental health indicators, we demonstrated that trajectory groups with high levels of compassionate self-responding were associated with greater life satisfaction, more happiness, better sleep quality, higher sleep quantity, and fewer negative emotions, as compared to lower trajectory groups. The results supported the idea that self-compassion during the COVID-19 pandemic could have favored better mental health indicators and could possibly be promoted as a psychological intervention in the general population.

Factors associated with infant mortality in Nigeria: A scoping review

by Loveth Dumebi Nwanze, Alaa Siuliman, Nuha Ibrahim

Background

Infant mortality persists as a global public health concern, particularly in lower-middle-income countries (LIMCs) such as Nigeria. The risk of an infant dying before one year of age is estimated to be six times higher in Africa than in Europe. Nigeria recorded an infant mortality rate of 72.2 deaths per 1,000 live births in 2020, in contrast to the global estimate of 27.4 per 1,000 live births. Several studies have been undertaken to determine the factors influencing infant mortality.

Objective

This scoping review sought to identify and summarise the breadth of evidence available on factors associated with infant mortality in Nigeria.

Methods

This review followed the five-stage principles of Arksey and O’Malley’s framework. Four electronic databases were searched with no limit to publication date or study type: Ovid MEDLINE, PubMed, CINAHL Complete, and Web of Science. Selected studies were imported into Endnote software and then exported to Rayyan software where duplicates were removed. Included articles were thematically analysed and synthesised using the socioecological model.

Results

A total of 8,139 references were compiled and screened. Forty-eight articles were included in the final review. At the individual level, maternal- and child-related factors were revealed to influence infant mortality; socioeconomic and sociocultural factors at the interpersonal level; provision and utilisation of health services, health workforce, hospital resources and access to health services at the organisational level; housing/neighbourhood and environmental factors at the community level; and lastly, governmental factors were found to affect infant mortality at the public policy level.

Conclusion

Factors related to the individual, interpersonal, organisational, community and public policy levels were associated with infant mortality in Nigeria.

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