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Abstract Background Obtaining evidence on comparative effectiveness and safety of widely prescribed drugs in a timely and cost-effective way is a major challenge for healthcare systems. Here, we describe the feasibility of the Evaluating Diuretics in Normal Care (EVIDENCE) study that compares a thiazide and thiazide-like diuretics for hypertension as an exemplar of a more general framework for efficient generation of such evidence. In 2011, the UK NICE hypertension guideline included a recommendation that thiazide-like diuretics (such as indapamide) be used in preference to thiazide diuretics (such as bendroflumethiazide) for hypertension. There is sparse evidence backing this recommendation, and bendroflumethiazide remains widely used in the UK. Methods Patients prescribed indapamide or bendroflumethiazide regularly for hypertension were identified in participating general practices. Allocation of a prescribing policy favouring one of these drugs was then randomly applied to the practice and, where required to comply with the policy, repeat prescriptions switched by pharmacy staff. Patients were informed of the potential switch by letter and given the opportunity to opt out. Practice adherence to the randomised policy was assessed by measuring the amount of policy drug prescribed as a proportion of total combined indapamide and bendroflumethiazide. Routinely collected hospitalisation and death data in the NHS will be used to compare cardiovascular event rates between the two policies. Results This pilot recruited 30 primary care practices in five Scottish National Health Service (NHS) Boards. Fifteen practices were randomised to indapamide (2682 patients) and 15 to bendroflumethiazide (3437 patients), a study population of 6119 patients. Prior to randomisation, bendroflumethiazide was prescribed to 78% of patients prescribed either of these drugs. Only 1.6% of patients opted out of the proposed medication switch. Conclusion The pilot and subsequent recruitment confirms the methodology is scalable within NHS Scotland for a fully powered larger study; currently, 102 GP practices (> 12,700 patients) are participating in this study. It has the potential to efficiently produce externally valid comparative effectiveness data with minimal disruption to practice staff or patients. Streamlining this pragmatic trial approach has demonstrated the feasibility of a random prescribing policy design framework that can be adapted to other therapeutic areas. Trial registration ISRCTN Registry, ISRCTN46635087 . Registered on 11 August 2017

Abstract Introduction Healthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-class, head-to-head comparisons of licensed medicines. For commonly prescribed drugs, even small differences in effectiveness or safety could have significant public health implications. However, conventional clinical trials that randomise individual subjects are costly and unwieldy. Such trials are also often criticised as having low external validity. We describe an approach to rapidly generate externally valid evidence of comparative safety and effectiveness using the example of two widely used diuretics for the management of hypertension. Methods and analysis The EVIDENCE (Evaluating Diuretics in Normal Care) study has a prospective, cluster-randomised, open-label, blinded end-point design. By randomising prescribing policy in primary care practices, the study compares the safety and effectiveness of commonly used diuretics in treating hypertension. Participating practices are randomised 1:1 to a policy of prescribing either indapamide or bendroflumethiazide when clinically indicated. Suitable patients who are not already taking the policy diuretic are switched accordingly. All patients taking the study medications are written to explaining the rationale for changing the prescribing policy and notifying them they can opt-out of any switch. The prescribing policies’ effectiveness and safety will be compared using rates of major adverse cardiovascular events (hospitalisation with myocardial infarction, heart failure or stroke or cardiovascular death), routinely collected in national healthcare administrative datasets. The study will seek to recruit 250 practices to provide a study population of approximately 50,000 individuals with a mean follow-up time of two years. A primary intention-to-treat time-to-event analysis will be used to estimate the relative effect of the two policies. Ethics and dissemination EVIDENCE has been approved by the East of Scotland Research Ethics Service (17/ES/0016, current approved protocol version 5, 26 August 2021). The results will be disseminated widely in peer reviewed journals, guideline committees, National Health Service (NHS) organisations and patient groups. Trial registration ISRCTN 46635087 . Registered on 11 August 2017 (pre-recruitment).

Medical microbiology courses focus on clinically relevant organisms, but designing laboratory experiments that mimic clinical specimens can be challenging. Many clinical specimens produce multi-organism cultures, which are difficult to reproducibly create in the academic laboratory. With experience with only single organism cultures, students may find it challenging to transition to the clinical laboratory where they must identify pathogens and normal flora from mixed cultures. Here, we present protocols for the creation of multi-organism cultures for mock wound, stool, urine, and throat cultures with medically relevant bacteria that allow these principles to be taught in an academic laboratory prior to clinical experiences.

Abstract Background The use of telehealth has proliferated to the point of being a common and accepted method of healthcare service delivery. Due to the rapidity of telehealth implementation, the evidence underpinning this approach to healthcare delivery is lagging, particularly when considering the uniqueness of some service users, such as those in rural areas. This research aimed to address the current gap in knowledge related to the factors critical for the successful delivery of telehealth to rural populations. Methods This research used a qualitative descriptive design to explore telehealth service provision in rural areas from the perspective of clinicians and describe factors critical to the effective delivery of telehealth in rural contexts. Semi-structured interviews were conducted with clinicians from allied health and nursing backgrounds working in child and family nursing, allied health services, and mental health services. A manifest content analysis was undertaken using the Framework approach. Results Sixteen health professionals from nursing, clinical psychology, and social work were interviewed. Participants mostly identified as female (88%) and ranged in age from 26 to 65 years with a mean age of 47 years. Three overarching themes were identified: (1) Navigating the role of telehealth to support rural healthcare; (2) Preparing clinicians to engage in telehealth service delivery; and (3) Appreciating the complexities of telehealth implementation across services and environments. Conclusions This research suggests that successful delivery of telehealth to rural populations requires consideration of the context in which telehealth services are being delivered, particularly in rural and remote communities where there are challenges with resourcing and training to support health professionals. Rural populations, like all communities, need choice in healthcare service delivery and models to increase accessibility. Preparation and specific, intentional training for health professionals on how to transition to and maintain telehealth services is a critical factor for delivery of telehealth to rural populations. Future research should further investigate the training and supports required for telehealth service provision, including who, when and what training will equip health professionals with the appropriate skill set to deliver rural telehealth services.

Abstract In the United Kingdom, roughly 1 in 250 babies are stillborn each year. Most women who experience stillbirth become pregnant again – 80% within a year of loss. Presently, obstetric-led care is recommended; though there is a growing body of evidence to support provision of specialist services. The Rainbow Clinic is a specialist antenatal service providing care for pregnancies after loss incorporating clinical and psychological care. This study aimed to assess patient experience at the Rainbow Clinic and identify areas for clinical improvement. A 13-item questionnaire was distributed to pregnant women who attended the Rainbow Clinics at the Oxford Road and Wythenshawe sites of Saint Mary’s Hospital, Manchester, UK between July 2016 and June 2021. Descriptive statistics and unpaired t-test were used for quantitative data and summative content analysis for qualitative data. Four-hundred and fifty-six women completed the questionnaire. The mean patient experience score per quarter was stable with an average of 21.1 (± 3.0) for the five years, with a maximum attainable score of 25. The COVID-19 pandemic had no effect on patient experience at the Rainbow Clinic (pre-pandemic vs. during-pandemic: mean 21.2 v 21.3; p = 0.75). Free-text responses demonstrated women felt positively about the antenatal care received. Identified areas for improvement included “more awareness of the [Rainbow] sticker” to ensure women with previous loss are identified; increased publicity of the Rainbow Clinic services; developing more clinics at different locations to improve accessibility; and continuing specialist input into intrapartum care. Specialist antenatal care provided by the Rainbow Clinic was rated as of a high standard. Potential future improvements include sticker alterations (or other mechanisms to identify women who have experienced a previous loss) and develop increased awareness of the clinic in other institutions.

Abstract Background We previously found an association between rurality and death by suicide, where those living in rural areas were more likely to die by suicide. One potential reason why this relationship exists might be travel time to care. This paper examines the relationship between travel time to both psychiatric and general hospitals and suicide, and then determine whether travel time to care mediates the relationship between rurality and suicide. Methods This is a population-based nested case-control study. Data from 2007 to 2017 were obtained from administrative databases held at ICES, which capture all hospital and emergency department visits across Ontario. Suicides were captured using vital statistics. Travel time to care was calculated from the resident’s home to the nearest hospital based on the postal codes of both locations. Rurality was measured using Metropolitan Influence Zones. Results For every hour in travel time a male resides from a general hospital, their risk of death by suicide doubles (AOR = 2.08, 95% CI = 1.61–2.69). Longer travel times to psychiatric hospitals also increases risk of suicide among males (AOR = 1.03, 95%CI = 1.02–1.05). Travel time to general hospitals is a significant mediator of the relationship between rurality and suicide among males, accounting for 6.52% of the relationship between rurality and increased risk of suicide. However, we also found that there is effect modification, where the relationship between travel time and suicide is only significant among males living in urban areas. Conclusions Overall, these findings suggest that males who must travel longer to hospitals are at a greater risk of suicide compared to those who travel a shorter time. Furthermore, travel time to care is a mediator of the association between rurality and suicide among males.

Abstract Microneedling is a popular skin resurfacing and rejuvenation procedure. In order to develop better adjunct products for consumers, there is a scientific need to establish greater understanding of the mechanism in which microneedling stimulates regeneration within skin. The purpose of this study is to develop a physiologically relevant ex vivo tissue model which closely mimics the actual microneedling procedure to elucidate its mechanism of action. In this study, human ex vivo skin was subjected to microneedling treatment and cultured for 6 days. Histological analysis demonstrated that the ex vivo skin was able to heal from microneedling injury throughout the culture period. Microneedling treatment stimulated proliferation and barrier renewal of the skin. The procedure also increased the levels of inflammatory cytokines and angiogenic growth factors in a dynamic and time dependent fashion. The tissue demonstrated hallmark signs of epidermal regeneration through morphological and molecular changes after the treatment. This is one of the first works to date that utilizes microneedled ex vivo skin to demonstrate its regenerative behavior. Our model recapitulates the main features of the microneedling treatment and enables the evaluation of future cosmetic active ingredients used in conjunction with microneedling.

Traditional research in inflammatory dermatoses has relied on animal models and reconstructed human epidermis to study these conditions. However, these models are limited in replicating the complexity of real human skin and reproducing the intricate pathological changes in skin barrier components and lipid profiles. To address this gap, we developed experimental models that mimic various human inflammatory skin phenotypes. Human ex vivo skins were stimulated with various triggers, creating models for inflammation-induced angiogenesis, irritation response, and chronic T-cell activation. We assessed the alterations in skin morphology, cellular infiltrates, cytokine production, and epidermal lipidomic profiles. In the pro-angiogenesis model, we observed increased mast cell degranulation and elevated levels of angiogenic growth factors. Both the irritant and chronic inflammation models exhibited severe epidermal disruption, along with macrophage infiltration, leukocyte exocytosis, and heightened cytokine levels. Lipidomic analysis revealed minor changes in the pro-angiogenesis model, whereas the chronic inflammation and irritant models exhibited significant decreases in barrier essential ceramide subclasses and a shift toward shorter acyl chain lengths (

This article focuses on certified B Corporations in Atlantic Canada and attempts to understand the benefits in being certified. Telephone interviews and a questionnaire were used to solicit recipients’ feedback on the delivery of their brand promises and overall satisfaction of the benefits to being certified. The study finds that the main motivation behind being certified is validation in the market that the business is adhering to certain social and environmental standards. Interviewees view certification as a strategy to demonstrate that their corporate social responsibility activities are being performed as promised. This article shows how organizations that have opted in to holding the certification as a unique differentiator distinguish themselves from other companies in the marketplace. Résumé Cet article porte sur les entreprises du Canada atlantique ayant obtenu la certification « B Corp ». Il cherche à comprendre les avantages de celle-ci. Des entrevues téléphoniques et un questionnaire ont été utilisés pour solliciter les commentaires de représentants d’organismes certifiés sur la réalisation des promesses de la certification « B Corp » et leur satisfaction globale relative à celle-ci. L’étude montre que la principale motivation pour obtenir la certification est de se faire reconnaître sur le marché comme une entreprise qui adhère à certaines normes sociales et environnementales. Les personnes interrogées considèrent la certification comme une stratégie visant à démontrer que leurs entreprises réalisent leurs activités de responsabilité sociale comme promis. Cet article montre comment les organisations qui ont choisi de détenir la certification comme un facteur de différenciation unique se distinguent des autres entreprises sur le marché. Keywords / Mots clés : B Corporation, B Lab, environmental standards, social standards, corporate social responsibility / B Corporation, B Lab, normes environnementales, normes sociales, responsabilité sociale de l’entreprise

Increasing human papillomavirus (HPV) vaccine uptake remains a challenge. We compared reasons for HPV vaccine acceptance between two Southern California pediatric clinics serving diverse populations: an academically affiliated resident clinic that offered little continuity of care (n = 53) and a private-practice clinic with well-established physician–patient relationships (n = 200). We found strong doctor recommendation and information dissemination about the importance of HPV vaccination were the most important drivers of acceptance across these distinct settings. The top-cited reasons for vaccine acceptance also varied by gender, language (English vs. Spanish), and clinic type. Findings point to the need for (1) robust provider education on vaccines, vaccine-preventable diseases, and vaccine hesitancy and (2) increased efforts to raise public awareness of the importance of HPV vaccination.

Summary: Alcohol use is a major risk factor for death and disease worldwide and alcohol-related harms appear to be more prevalent in rural and remote, relative to urban, communities. This Review synthesised international research on rural–urban disparities in hazardous and harmful alcohol use and risk factors for these outcomes within rural and remote communities. 280 studies from 49 countries were included in the Scoping Review. Most studies (60%) found rural, relative to urban, residence to be associated with an increased likelihood of hazardous alcohol use or alcohol-related harm. This proportion increased between 1990 and 2019 and varied by country, age group, and outcome type, being highest in Australia, among young adults, and for more severe alcohol-related harms, such as drink driving and alcohol-related suicide. Improved public health strategies to reduce the burden of alcohol use in rural communities are required but their efficacy will depend on how well they are tailored to the unique needs of the region they are implemented in.

The objective of the present study was to evaluate the contribution of voluntary fortified foods and supplements to reducing micronutrient shortfalls in the UK population. A secondary analysis of the UK National Diet and Nutrition Survey was conducted (2012/13–2013/14, N 2546, 1·5–95 years). Micronutrient intakes were derived from food consumption intake data and food composition data and calculated as the proportion below or above the Dietary Reference Values for males and females of different age groups, for those on a base diet only, users of fortified foods but no supplements and users of fortified foods and supplements. Of the population consuming a base diet only, 21–45 % and 5–29 % fell below the Estimated Average Requirement (EAR) for minerals and vitamins, respectively. About 3–13 % fewer consumers of fortified foods fell below the EAR for vitamins and minerals. Supplements barely reduced the prevalence of intakes below the EAR. Among supplement non-users and users, 99 and 96 % failed to meet the reference intakes for vitamin D. More women than men were at risk of inadequacies of micronutrient intakes. The prevalence of inadequacies declined with increasing age. Voluntary fortified foods but not supplements made a meaningful contribution to intakes of vitamin and minerals, without risk of unacceptably high intakes. These insights may help the UK to define approaches to address micronutrients of concern in vulnerable groups.

Online extremism, or the use of information technology to profess attitudes devaluing others based on a characteristic such as race, religion, gender, or sexuality, is a growing problem. This has led to myriad harmful effects for some who are exposed to online hate. A critical first step toward stemming the tide of online hate is understanding factors associated with its creation and spread. To that end, this analysis examines factors associated with joining an ongoing attack against a targeted group online. We use insights from four leading criminological theories routine activity theory, social control theory, general strain theory, and social learning/differential association theory - to investigate who is likely to join an attack on a targeted group when they view such an attack occurring. Using data from a national sample of 15 36-year-old Internet users, we conduct an ordinal logistic regression analysis. Results show support for social control theory and strain theory, as low levels of self-control and online strain are both positively correlated with joining an online attack. Similarly, we find support for the applicability of social learning theory; close engagement with online friends and groups is related to an increased likelihood of joining in online hate. Routine activity theory, however, is less relevant for understanding our outcome. Taken together, our findings shed light on factors associated with the perpetuation of online hate, and, in doing so, offer avenues for reducing its growth.

Review of the book Birth Control Battles: How Race and Class Divided American Religion, by Melissa J. Wilde.

Abstract Background Media depictions and laws passed in state legislatures regulating abortion suggest abortion-related medical emergencies are common. An accurate understanding of abortion-related emergencies is important for informing policy and practice. We assessed the incidence of abortion-related emergency department (ED) visits in the United States (U.S.). Methods We used a retrospective observational study design using 2009–2013 data from the Nationwide Emergency Department Sample, a nationally representative sample of U.S. ED visits from 947 to 964 hospitals across the U.S. per year. All ED visits among women of reproductive age (15–49) were included. We categorized ED visits by abortion relatedness and treatments received, and assessed whether the visit was for a major incident (defined as requiring blood transfusion, surgery, or overnight inpatient stay). We estimated the proportion of visits that were abortion-related and described the characteristics of patients making these visits, the diagnoses and subsequent treatments received by these patients, the sociodemographic and hospital characteristics associated with the incidents and observation care only (defined as receiving no treatments), and the rate of major incidents for all abortion patients in the U.S. Results Among all ED visits by women aged 15–49 (189,480,685), 0.01% (n = 27,941) were abortion-related. Of these visits, 51% (95% confidence interval, 95% CI 49.3–51.9%) of the women received observation care only. A total of 20% (95% CI 19.3–21.3%) of abortion-related ED visits were for major incidents. One-fifth (22%, 95% CI 20.9–23.0%) of abortion-related visits resulted in admission to the same hospital for abortion-related reasons. Of the visits, 1.4% (n = 390, 95% CI 1.1–1.7%) were potentially due to attempts at self-induced abortion. In multivariable models, women using Medicaid (adjusted odds ratio, AOR 1.28, 95% CI 1.08–1.52) and women with a comorbid condition (AORs 2.47–4.63) had higher odds of having a major incident than women using private insurance and those without comorbid conditions. During the study period, 0.11% of all abortions in the U.S. resulted in major incidents as seen in EDs. Conclusions Abortion-related ED visits comprise a small proportion of women’s ED visits. Many abortion-related ED visits may not be indicated or could have been managed at a less costly level of care. Given the low rate of major incidents, perceptions that abortion is unsafe are not based on evidence.

Background: Angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACE-I/ARB) improve outcomes in patients with heart failure and reduced left-ventricular (LV) systolic function. However, these medications can cause a rise in serum creatinine and their benefits in patients with HF accompanied by kidney disease are less certain. Objective: To characterize associations between estimated glomerular filtration rate (eGFR), patterns of ACE-Is and ARBs use, and 1-year survival following hospitalization for heart failure (HF). Design: We formed a retrospective cohort study of patients admitted with HF and followed HF medication prescriptions using the pharmaceutical information network, stratified by discharge eGFR. Setting: Cardiology services in 3 centers in Southern Alberta, Canada. Patients: The study cohort included patients admitted to hospital with a clinical diagnosis of HF. Measurements: eGFR was determined from inpatient laboratory data prior to discharge. Outpatient prescription data prior to and following the index hospitalization was obtained using the Pharmaceutical Information Network of Alberta and survival was determined from provincial vital statistics. Methods: Characteristics of the HF cohort were obtained from the Admissions Module of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Multivariable Cox proportional hazards models were used to evaluate the association between time-varying ACE-I/ARB use, and mortality, and to test whether eGFR modified this association. Results: Totally, 1404 patients were included. Within the first 3 months following discharge, ACE-I/ARBs were used in 71%, 67%, 62%, and 52% for those with eGFR > 90, 45-89, 30-44, and < 30 mL/min/1.73 m 2 , respectively, with differences in use persisting after 1 year of follow-up. Patients with eGFR < 45 mL/min/1.73 m 2 had significantly lower rates of ACE-I/ARB use following hospitalization. In adjusted models, ACE-I/ARB use following discharge was associated with 25% lower risk of mortality (Hazard Ratio [HR]: 0.75, 95% confidence interval [CI]: 0.61-0.92; P < 0.01), without evidence that this association differed by eGFR ( P = 0.75). Limitations: LV function measurements were not available for the cohort. Due to the observation design of the study, treatment-selection bias may be present. Conclusion: Patients with HF and reduced eGFR at time of hospital discharge were less likely to receive ACE-I/ARB despite these medications being associated with lower mortality independent of eGFR. These findings demonstrate the need for further research on strategies for safe use of ACE-I and ARB in patients with HF and kidney disease.