Effectiveness and safety of glecaprevir/pibrentasvir for 8 weeks in the treatment of patients with acute hepatitis C: A single-arm retrospective study.

BACKGROUND AND AIMS: No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection. APPROACH AND RESULTS: This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection. Analyses were conducted on a full analysis set (FAS; all enrolled) and modified FAS (FAS excluding nonvirologic failures). The primary end point (modified FAS) was sustained virologic response at posttreatment week 12 (SVR12) with superiority to 92.6% threshold determined by historic chronic HCV G/P SVR12 rates. Secondary end points (FAS) included SVR12, on-treatment virologic failure, posttreatment relapse, and reinfection. Adverse events and safety laboratory values were assessed.Overall, 202 adults were enrolled; in the modified FAS, 150/151 (99.3%; 95% CI: 96.3-99.9) achieved SVR12, demonstrating superiority to efficacy threshold. In the FAS, the SVR12 rate was 74.3% and the on-treatment virologic failure rate was 0%. Relapse and reinfection rates after the final treatment visit (FAS) were 0.5% and 3%, respectively; 39 patients had missing SVR12 data. No on-treatment alanine aminotransferase elevations > 3 × upper limit of normal with total bilirubin > 2 × upper limit of normal were reported. All 53 patients with alanine aminotransferase Grade ≥ 2 at baseline improved to Grade 0/1 on treatment. No adverse eventss of hepatic decompensation/failure or leading to G/P discontinuation occurred. Two patients had serious adverse events unrelated to G/P. CONCLUSIONS: Eight-week G/P therapy was effective and well-tolerated in patients with acute HCV infection. Data support further investigation of G/P in acute HCV to shorten care cascades, reduce transmission, and support HCV elimination.

Reported adverse events related to use of hepatitis C virus direct-acting antivirals with opioids: 2017-2021.

INTRODUCTION: Due to concerns over potential interactions between some hepatitis C direct-acting antivirals (DAAs) and opioids, we describe adverse event (AE) reports of concomitant use of opioids and DAAs. METHODS: AEs reported (July 28, 2017-December 31, 2021) with the administration of the DAAs glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir/voxilaprevir, and elbasvir/grazoprevir as suspect products were downloaded from the US Food and Drug Administration AE Reporting System Public Dashboard. The number of AE reports containing opioids (fentanyl, hydrocodone, oxycodone) as co-suspect products/concomitant products were counted and summarized by severity, reporting country and whether an outcome of death was reported. Overdose AEs were counted irrespective of opioid use, and changes over time were assessed. RESULTS: In total, 40 AEs were reported for DAAs and concomitant fentanyl use, 25 (62.5%) were in the USA, 35 (87.5%) were considered serious, and 14 (35.0%) resulted in death; and 626 were reported with concomitant oxycodone/hydrocodone use, 596 (95.2%) were in the USA, 296 (47.3%) were considered serious, and 28 (4.5%) resulted in death. There were 196 overdose AEs (32 [16%] deaths) declining from 2018 (N = 56) to 2021 (N = 29). CONCLUSIONS: Treating people with hepatitis C virus (HCV) infection who use drugs is key to achieving HCV elimination. Low numbers of DAA AE reports with opioids may provide reassurance to prioritize HCV treatment in this population. These data contribute to evidence supporting the continued scale-up of DAA treatment among people who use drugs to achieve HCV elimination goals.

Interventions that aim to increase social participation through recreation or leisure activity for adults with moderate to severe traumatic brain injury: a scoping review.

PURPOSE: Social isolation and reduced social participation are common after traumatic brain injury (TBI). Developing interventions that aim to increase social participation through recreation or leisure activities continues to be challenging. This scoping review was conducted to provide an overview of interventions used to increase social participation through in-person recreation or leisure activity for adults with moderate to severe TBI living in the community. METHODS: Using the Arksey and O'Malley framework, a scoping review of the literature published from 2005 to 2023 was conducted across four databases: Medline, CINAHL, PsycINFO and Scopus. Quality appraisals were conducted for included studies. RESULTS: Following the removal of duplicates, 10,056 studies were screened and 52 were retained for full-text screening. Seven papers were included in the final review. Studies varied with respect to the type of intervention and program outcomes. The interpretation was impeded by study quality, with only two studies providing higher levels of evidence. Barriers and facilitators to successful program outcomes were identified. CONCLUSIONS: Few studies with interventions focused on increasing social participation in leisure or recreation activity were identified. Further research incorporating mixed methods and longitudinal design to evaluate effectiveness over time is needed to build the evidence base for increasing social participation through leisure activity.

There is evidence to support participating in recreation and leisure activities that involve interactions with others can increase social participation outcomes for adults with moderate to severe traumatic brain injury.Participating in leisure-based interventions not only provides opportunities for social connection but may also impact positively on personal wellbeing, enjoyment, and confidence.Understanding the range of personal, practical, support, and activity factors that can facilitate or obstruct participation in leisure or recreational activity programs at an individual level may improve social participation outcomes.Measuring the impact of an intervention for social participation should include post-intervention changes across outcome domains and over time.

Assessment of Drug-Drug Interaction Risk Between Intravenous Fentanyl and the Glecaprevir/Pibrentasvir Combination Regimen in Hepatitis C Patients Using Physiologically Based Pharmacokinetic Modeling and Simulations.

INTRODUCTION: An unsafe injection practice is one of the major contributors to new hepatitis C virus (HCV) infections; thus, people who inject drugs are a key population to prioritize to achieve HCV elimination. The introduction of highly effective and well-tolerated pangenotypic direct-acting antivirals, including glecaprevir/pibrentasvir (GLE/PIB), has revolutionized the HCV treatment landscape. Glecaprevir is a weak cytochrome P450 3A4 (CYP3A4) inhibitor, so there is the potential for drug-drug interactions (DDIs) with some opioids metabolized by CYP3A4, such as fentanyl. This study estimated the impact of GLE/PIB on the pharmacokinetics of intravenous fentanyl by building a physiologically based pharmacokinetic (PBPK) model. METHODS: A PBPK model was developed for intravenous fentanyl by incorporating published information on fentanyl metabolism, distribution, and elimination in healthy individuals. Three clinical DDI studies were used to verify DDIs within the fentanyl PBPK model. This model was integrated with a previously developed GLE/PIB PBPK model. After model validation, DDI simulations were conducted by coadministering GLE 300 mg + PIB 120 mg with a single dose of intravenous fentanyl (0.5 µg/kg). RESULTS: The predicted maximum plasma concentration ratio between GLE/PIB + fentanyl and fentanyl alone was 1.00, and the predicted area under the curve ratio was 1.04, suggesting an increase of only 4% in fentanyl exposure. CONCLUSION: The administration of a therapeutic dose of GLE/PIB has very little effect on the pharmacokinetics of intravenous fentanyl. This negligible increase would not be expected to increase the risk of fentanyl overdose beyond the inherent risks related to the amount and purity of the fentanyl received during recreational use.

Impact of process and composition of formulas for elderly on in vitro digestion using the dynamic DIDGI® model.

Due to the lower efficiency of the elderly digestion system, new formulations are needed in order to increase the bioaccessibility of macronutrients. The aim of the work was to evaluate the effect of the process of protein sources production using either liquid (F2) vs spray dried milk proteins (F1/F3) and the source of lipids (vegetable oil (F1) vs mix of vegetable oil + bovine milk cream (F2/F3)) ingredients on the macronutrient digestion of three experimental elderly formulas. The dynamic in vitro digestion model DIDGI®, was adapted to simulate the digestive conditions of the elderly. An exhaustive review of the literature was carried out in order to simulate as closely as possible the elderly digestive parameters and constituted the starting point towards a consensus in vitro digestion model that will be proposed soon by the INFOGEST scientific network. The three experimental formulas (F1/F2/F3) differing by the composition and process applied were submitted to the DIDGI® dynamic in vitro digestion over four hours using parameters adapted to the elderly. The three formulas were compared in terms of proteolysis and lipolysis. A slight impact of the process (liquid vs spray-dried) on the degree of proteolysis at the end of digestion was observed with 50.8% for F2 compared to 56.8% for F1 and 52.9% for F3 with<5% of difference between the 3 formulas. Concerning the degree of lipolysis, the addition of bovine cream led to a lesser extent of lipolysis with 63.7 and 60.2% for F2 and F3 respectively versus 66.3% for F1 (containing only vegetable oil). Our results highlighted the beneficial input of the milk fat with a higher level of phospholipids and a lower ω6/ω3 PUFA ratio and can be a good alternative to the use of the vegetable fat in drinks for elderly people.

Clinic-Based Financial Coaching and Missed Pediatric Preventive Care: A Randomized Trial.

OBJECTIVES: Poverty is a common root cause of poor health and disrupts medical care. Clinically embedded antipoverty programs that address financial stressors may prevent missed visits and improve show rates. This pilot study evaluated the impact of clinic-based financial coaching on adherence to recommended preventive care pediatric visits and vaccinations in the first 6 months of life. METHODS: In this community-partnered randomized controlled trial comparing clinic-based financial coaching to usual care among low-income parent-infant dyads attending pediatric preventive care visits, we examined the impact of the longitudinal financial intervention delivered by trained coaches addressing parent-identified, strengths-based financial goals (employment, savings, public benefits enrollment, etc.). We also examined social needs screening and resource referral on rates of missed preventive care pediatric visits and vaccinations through the 6-month well-child visit. RESULTS: Eighty-one parent-infant dyads were randomized (35 intervention, 46 control); nearly all parents were mothers and more than one-half were Latina. The rate of missed visits among those randomized to clinic-based financial coaching was half that of controls (0.46 vs 1.07 missed of 4 recommended visits; mean difference, 0.61 visits missed; P = .01). Intervention participants were more likely to have up-to-date immunizations each visit (relative risk, 1.26; P = .01) with fewer missed vaccinations by the end of the 6-month preventive care visit period (2.52 vs 3.8 missed vaccinations; P = .002). CONCLUSIONS: In this pilot randomized trial, a medical-financial partnership embedding financial coaching within pediatric primary care improved low-income families' adherence to recommended visits and vaccinations. Clinic-based financial coaching may improve care continuity and quality in the medical home.

Early calcium and cardiac contraction defects in a model of phospholamban R9C mutation in zebrafish.

The phospholamban mutation Arg 9 to Cys (R9C) has been found to cause a dilated cardiomyopathy in humans and in transgenic mice, with ventricular dilation and premature death. Emerging evidence suggests that phospholamban R9C is a loss-of-function mutation with dominant negative effect on SERCA2a activity. We imaged calcium and cardiac contraction simultaneously in 3 and 9 days-post-fertilization (dpf) zebrafish larvae expressing plnbR9C in the heart to unveil the early pathological pathway that triggers the disease. We generated transgenic zebrafish lines expressing phospholamban wild-type (Tg(myl7:plnbwt)) and phospholamban R9C (Tg(myl7:plnbR9C)) in the heart of zebrafish. To measure calcium and cardiac contraction in 3 and 9 dpf larvae, Tg(myl7:plnbwt) and Tg(myl7:plnbR9C) fish were outcrossed with a transgenic line expressing the ratiometric fluorescent calcium biosensor mCyRFP1-GCaMP6f. We found that PlnbR9C raised calcium transient amplitude, induced positive inotropy and lusitropy, and blunted the ß-adrenergic response to isoproterenol in 3 dpf larvae. These effects can be attributed to enhanced SERCA2a activity induced by the PlnbR9C mutation. In contrast, Tg(myl7:plnbR9C) larvae at 9 dpf exhibited ventricular dilation, systolic dysfunction and negative lusitropy, hallmarks of a dilated cardiomyopathy in humans. Importantly, N-acetyl-L-cysteine rescued this deleterious phenotype, suggesting that reactive oxygen species contribute to the pathological pathway. These results also imply that dysregulation of calcium homeostasis during embryo development contributes to the disease progression at later stages. Our in vivo model in zebrafish allows characterization of pathophysiological mechanisms leading to heart disease, and can be used for screening of potential therapeutical agents.

Where Are They Now: The Narratives of Children Who Lost a Parent on 9/11.

There is a paucity of literature examining the experiences of children who lost a parent on 9/11. The primarily quantitative research has not allowed for a deeper understanding of how children who lost a parent on 9/11 make meaning of their experiences, especially in the context of a national tragedy. This study investigates how eight children who were between the ages of 5 and 12 when they lost a parent on 9/11 developed a personal narrative about this loss in the context of the collective narrative about 9/11. Using narrative inquiry, cases demonstrated patterns of narrative development about grief, tragedy, and collective themes of American exceptionalism, patriotism, triumph, and resiliency. These cases highlight de-personalized narratives of grief, tension between the grand narrative provided to them and their personal story of loss, and distance between the reality of their loss and the collective meaning-making of the tragedy. This study extends Bronfenbrenner's (1977) ecological systems theory by highlighting how a lack of bidirectionality between larger social and cultural systems and the individual negatively impacts personal experiences of grief and loss.

Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension.

INTRODUCTION: High efficacy and safety of 8-week glecaprevir/pibrentasvir (G/P) therapy was seen in hepatitis C (HCV)-infected, treatment-naïve (TN), compensated cirrhosis (CC) patients in EXPEDITION-8. To provide further understanding of the efficacy of G/P treatment in HCV-infected TN patients with CC and clinical evidence of portal hypertension (PHT), this analysis focused on differences in sustained virologic response at post-treatment week 12 (SVR12) between 8-week and 12-week G/P treatment groups in patients with PHT, and on differences in safety outcomes between PHT and non-PHT groups. METHODS: Data were derived from an ad hoc subgroup analysis of the EXPEDITION-8 study for patients receiving 8 weeks of G/P therapy, and pooled patient-level data from nine clinical studies for patients receiving 12 weeks of therapy. Evidence of PHT included at least one of the following at baseline: FibroScan ≥ 20 kPa, platelets < 100 × 109/L, or medical history consistent with PHT. The primary efficacy endpoint was SVR12; adverse events (AEs) consistent with hepatic decompensation were assessed. RESULTS: PHT was identified in 60.6% (208/343) and 57.1% (224/392) of the 8- and 12-week groups, respectively. For those with PHT, SVR12 was 97.6% (203/208) and 98.7% (221/224) with 8- and 12-week treatment, respectively (intention-to-treat population). For those without PHT, 97.8% (132/135) in the 8-week group and 97.6% (164/168) in the 12-week group achieved SVR12. Eight patients with PHT, and seven without, did not achieve SVR12. Similar rates of AEs were observed in the PHT and non-PHT groups. Three cases of hepatic decompensation in the PHT group, unrelated to G/P according to the investigators, were reported. CONCLUSION: G/P treatment for 8 or 12 weeks was equally efficacious in HCV patients with features of PHT. Safety outcomes were similar between PHT and non-PHT groups, with G/P treatment well tolerated across groups. NCTS: NCT03089944, NCT02642432, NCT02738138, NCT02243293, NCT02651194, NCT03235349, NCT02707952, NCT02966795, NCT03069365, NCT03219216.

Modeling Human Cardiac Arrhythmias: Insights from Zebrafish.

Cardiac arrhythmia, or irregular heart rhythm, is associated with morbidity and mortality and is described as one of the most important future public health challenges. Therefore, developing new models of cardiac arrhythmia is critical for understanding disease mechanisms, determining genetic underpinnings, and developing new therapeutic strategies. In the last few decades, the zebrafish has emerged as an attractive model to reproduce in vivo human cardiac pathologies, including arrhythmias. Here, we highlight the contribution of zebrafish to the field and discuss the available cardiac arrhythmia models. Further, we outline techniques to assess potential heart rhythm defects in larval and adult zebrafish. As genetic tools in zebrafish continue to bloom, this model will be crucial for functional genomics studies and to develop personalized anti-arrhythmic therapies.

Multicenter Study Evaluating Nitrous Oxide Use for Labor Analgesia at High- and Low-Altitude Institutions.

BACKGROUND: Nitrous oxide (N2O) has been used nationally as an analgesic in many clinical settings. While neuraxial analgesia is still the most commonly used labor analgesic in the United States, there is increasing use of N2O in labor. Given the reduction in the partial pressure of gases at a higher altitude, N2O has been reported to have reduced analgesic properties. However, there is no study to date evaluating the impact of altitude on labor analgesia and N2O. METHODS: We conducted a multicenter retrospective data analysis of a N2O registry collected from 4 institutions over a 3-year period. We compared the impact of altitude on 50% N2O administration for labor analgesia, conversion rates to another analgesic modality, as well as collected side effect frequencies and conversion predictors. Multivariable regression models were used to compare clinical characteristics and outcomes between parturients at high and low altitudes, while adjusting for race, ethnicity, education, and age (logistic and linear regressions for categorical and quantitative outcomes, respectively). RESULTS: A total of 1856 laboring parturients (age 18-50) were included in the analysis. The odds of converting from 50% N2O to another analgesic modality had no statistically significant difference between high- versus low-altitude institutions (adjusted odds ratio [aOR], 1.13; 95% confidence interval [CI], 0.90-1.42; P = .3). Yet, when parturients at low altitude converted from N2O, they were more likely (aOR, 3.03; 95% CI, 1.59-5.88) to choose neuraxial analgesia instead of another analgesic modality when compared to high-altitude parturients. This is possibly due to higher epidural rates at the low-altitude institutions. When parturients at high altitude did convert into another modality, they were more likely (aOR, 2.19; 95% CI, 1.14-4.21) to convert due to inadequate pain relief compared to low-altitude parturients; however, missing data may have affected this finding. Laboring individuals at low altitude were significantly more likely to experience side effects (aOR, 2.13; 95% CI, 1.45-3.12). Those requiring labor augmentation, assisted vaginal, or cesarean delivery converted to neuraxial analgesia significantly more often than those that delivered via spontaneous vaginal delivery (P < .05) in both high- and low-altitude groups. CONCLUSIONS: This is the first study evaluating 50% N2O as a labor analgesic at high altitude. As expected, we found lower side effects at high altitude, likely due to the lower partial pressure of N2O. However, there was not a statistically significant increase in conversion from N2O to another analgesic modality at high altitude and no clinically significant differences in neonatal outcomes.

Cardioluminescence in Transgenic Zebrafish Larvae: A Calcium Imaging Tool to Study Drug Effects and Pathological Modeling.

Zebrafish embryos and larvae have emerged as an excellent model in cardiovascular research and are amenable to live imaging with genetically encoded biosensors to study cardiac cell behaviours, including calcium dynamics. To monitor calcium ion levels in three to five days post-fertilization larvae, we have used bioluminescence. We generated a transgenic line expressing GFP-aequorin in the heart, Tg(myl7:GA), and optimized a reconstitution protocol to boost aequorin luminescence. The analogue diacetylh-coelenterazine enhanced light output and signal-to-noise ratio. With this cardioluminescence model, we imaged the time-averaged calcium levels and beat-to-beat calcium oscillations continuously for hours. As a proof-of-concept of the transgenic line, changes in ventricular calcium levels were observed by Bay K8644, an L-type calcium channel activator and with the blocker nifedipine. The ß-adrenergic blocker propranolol decreased calcium levels, heart rate, stroke volume, and cardiac output, suggesting that larvae have a basal adrenergic tone. Zebrafish larvae treated with terfenadine for 24 h have been proposed as a model of heart failure. Tg(myl7:GA) larvae treated with terfenadine showed bradycardia, 2:1 atrioventricular block, decreased time-averaged ventricular calcium levels but increased calcium transient amplitude, and reduced cardiac output. As alterations of calcium signalling are involved in the pathogenesis of heart failure and arrhythmia, the GFP-aequorin transgenic line provides a powerful platform for understanding calcium dynamics.

Reflections from the COVID-19 pandemic on inequalities and patient and public involvement and engagement (PPIE) in social care, health and public health research.

Patient and public involvement and engagement (PPIE) has evolved to become widely established practice in social care, health and public health research in the UK. The COVID-19 pandemic has caused rapid change in practice in PPIE, notably in moving from face-to-face meetings to virtual ones. This has opened a space for reflecting on established PPIE practice, but there is a risk this is conducted too narrowly, such as only weighing our preferences and the relative pros and cons with regard to in-person versus virtual meetings. The pandemic has also demonstrated the wide inequalities in society, and hence, we argue that an inequalities lens ought to guide a deeper and wider reflection on PPIE practice. We do not seek to criticize practice pre- or during the pandemic, but to encourage using the inequalities lens as a means of encouraging debate and focusing energy on a more rigorous review of PPIE practice to widen involvement in social care, health and public health research.

COVID-19 and the tsunami of information.

Coronavirus disease-2019 (COVID-19) is the infectious disease caused by the recently discovered coronavirus, SARS-CoV2. This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. The number of publications with regard to COVID-19-related information is exponentially increasing, but there are also some retracted papers appearing on PubMed, including those retracted from The Lancet Global Health and the New England Journal of Medicine. In a PubMed search for "COVID," there were 1595 articles by April 1, 2020. As of June 30, the number of articles has now reached 25,913. In this editorial, 4 specific areas of information are looked at but the principles apply to many other areas of medicine. The specifics looked at are PPE for tracheostomy, testing for COVID-19, pregnancy and COVID-19, and surgical expectations during redeployment. We must make no mistake that we are seeing a disease that modern medicine has never encountered before. This article is not aimed at belittling or dismissing any of the advice of the Royal Colleges' or PHE advice, but it demonstrates the tsunami of information and the ambiguity that surgeons are experiencing throughout the UK right now. This is unlikely to be the end of progression regarding healthcare planning and development for unencountered viruses9. In the next few months and beyond, there are likely to be adaptions and revisions of more documents advising on various aspects of healthcare with regard to COVID-19 management and for possible future viruses not yet seen by the modern world before.

Finding Goal Focus With People With Severe Traumatic Brain Injury in a Person-Centered Multi-Component Community Connection Program (M-ComConnect).

Background and Objectives: Loss of social connections in the community is a common consequence of severe traumatic brain injury (TBI), resulting in reduced well-being and quality of life. M-ComConnect is an individualized multi-component community connection intervention with the key objectives of increasing social activity, developing social relationships, and supporting community participation following severe TBI. As part of the M-ComConnect approach, semi-structured initial interviews were conducted to develop a holistic understanding of each participant and their goal focus for the project. In this paper we describe how clinicians worked with participants to identify a desired community-based social activity in which to participate. Method: Transcripts of initial interviews between participant and clinician were analyzed using the phases of reflexive thematic analysis developed by Braun and Clarke. Participants were ten individuals aged between 24 and 75 with severe TBI. All were living in the community and reported reduced social connections since their TBI. The aim of the analysis was to evaluate the skills and strategies used by clinicians in their interactions with participants to derive goal focus for the program. Results: Thematic analysis of initial interview data revealed three main categories and fourteen sub-categories of clinical strategies. These were: (1) Humanizing (curiosity; demonstrating respect and empathy; providing compliments and affirmations; simple reflections; revealing aspects of self; and humor and laughter), (2) Empowering (emphasizing choice and control; highlighting strengths; identifying roadblocks and reframing to reveal opportunities; and collaborative problem solving), and (3) Focusing (making suggestions; identifying preferences; working with ideas; and negotiating). These strategies aligned with the program's relational approach and supported the core processes of the goal-focussing framework, namely understanding and connecting with you, building a relationship, and working together with you to find focus. Conclusion: The goal-focusing framework and clinical strategies outlined provide guidance for clinicians working with people with TBI in the community and is a promising way to engage clients when focusing on individualized social activity-based goals.

Power, control, communities and health inequalities. Part II: measuring shifts in power.

In the health field, there is great interest in the role empowerment might play in reducing social inequalities in health. Empowerment is understood here as the processes of developing capabilities that individuals and/or communities need to exercise control over decisions and actions impacting on their lives and health. There is a fundamental problem, however, in identifying and measuring capabilities for collective control that emerge at the level of the collective, with much of the existing literature focusing on individual measures even where community-level processes are concerned. Collective measures need to capture the dynamics of interactions within and between groups, not simply aggregate individual-level measures. This article, Part 2 in a three-part series, takes up the challenge of identifying qualitative markers of capabilities for collective control. We applied the emancipatory power framework (EPF) reported in Part 1 of the series, to qualitative data generated during a longitudinal evaluation of a major English area-based empowerment initiative, the Big Local (BL). We identified empirical 'markers' of shifts towards greater collective control pertaining to each of the 'power' dimensions in the EPF-'power within', 'power with' and 'power to'-and markers of communities exercising 'power over' other institutions/community members. These markers can usefully be applied in the evaluation planning and evaluation of empowerment initiatives. Part 3 in the series uses these markers and a second analytical framework developed during our evaluation of BL to explore how power dynamics unfold in participatory spaces in BL neighbourhoods.

COVID-19 and telepsychiatry: Early outpatient experiences and implications for the future.

The COVID-19 pandemic has dramatically transformed the U.S. healthcare landscape. Within psychiatry, a sudden relaxing of insurance and regulatory barriers during the month of March 2020 enabled clinicians practicing in a wide range of settings to quickly adopt virtual care in order to provide critical ongoing mental health supports to both existing and new patients struggling with the pandemic's impact. In this article, we briefly review the extensive literature supporting the effectiveness of telepsychiatry relative to in-person mental health care, and describe how payment and regulatory challenges were the primary barriers preventing more widespread adoption of this treatment modality prior to COVID-19. We then review key changes that were implemented at the federal, state, professional, and insurance levels over a one-month period that helped usher in an unprecedented transformation in psychiatric care delivery, from mostly in-person to mostly virtual. Early quality improvement data regarding virtual visit volumes and clinical insights from our outpatient psychiatry department located within a large, urban, tertiary care academic medical center reflect both the opportunities and challenges of virtual care for patients and providers. Notable benefits have included robust clinical volumes despite social distancing mandates, reduced logistical barrieres to care for many patients, and decreased no-show rates. Finally, we provide clinical suggestions for optimizing telepsychiatry based on our experience, make a call for advocacy to continue the reduced insurance and regulatory restrictions affecting telepsychiatry even once this public health crisis has passed, and pose research questions that can help guide optimal utilization of telepsychiatry as mainstay or adjunct of outpatient psychiatric treatment now and in the future.

A 'strategy of resistance'? How can a place-based empowerment programme influence local media portrayals of neighbourhoods and what are the implications for tackling health inequalities?

Place-based stigma is linked with health and social harms, but few studies have assessed what actions may reduce these. Area-based programmes are one potential strategy but may exacerbate stigma by targeting disadvantaged neighbourhoods. We reviewed newspaper coverage in two stigmatised neighbourhoods to identify whether a programme funded in these localities influenced reporting. While both areas were dominated by negative coverage, the progamme provided an impetus for some positive stories over time and enabled community activists to articulate alternative narratives about where they lived, countering negative external portrayals. The involvement of residents should be central to strategies to tackle place-based stigma.

Nitrous Oxide Use During Labor: Satisfaction, Adverse Effects, and Predictors of Conversion to Neuraxial Analgesia.

INTRODUCTION: Women desire safe and effective choices for pain management during labor. Currently, neuraxial and opioid analgesia are the most common methods used in the United States. The purpose of this study was to investigate demographic characteristics, safety, and satisfaction in a cohort of parturients who used inhaled nitrous oxide (N2 O) analgesia and to determine predictors of conversion from N2 O to neuraxial analgesia. METHODS: This was a prospective chart review study. Individuals aged at least 18 years who used inhaled N2 O during the first or second stage of labor between March 1, 2016, and July 23, 2017, on the labor and delivery unit of one academic medical center (N = 463) and their neonates were included. Data describing maternal and neonatal factors are reported. Logistic regression and chi-square tests were used to model the effects of oxytocin augmentation, labor induction, parity, prior cesarean birth, pre-N2 O cervical dilatation, and post-N2 O cervical dilatation on the odds of conversion from N2 O to neuraxial analgesia. RESULTS: In this cohort, 31% who chose N2 O for analgesia did not convert to any other analgesic method. Significant positive predictors for conversion from N2 O to neuraxial analgesia included labor induction (odds ratio [OR], 2.9; 95% CI, 1.7-5.0), oxytocin augmentation (OR, 3.1; 95% CI, 1.6-6.0), and labor after cesarean (OR, 6.4; 95% CI, 2.5-16.5). Multiparity (OR, 0.4; 95% CI, 0.2-0.6) and post-N2 O cervical dilatation (OR, 0.8; 95% CI, 0.7-0.9) were negative predictors. Adverse effects related to N2 O use during labor were rare (8%) and were not a significant reason for conversion to neuraxial analgesia. Parturients had moderately high satisfaction with N2 O for pain management (11-point scale, mean [SD], 7.4 [2.9]). Five-minute Apgar scores were 7 or greater in 97.8% of the newborns. DISCUSSION: Understanding predictors of conversion from inhaled N2 O to neuraxial analgesia may assist perinatal care providers in their discussions with women about analgesia options during labor. N2 O is a useful, safe option for labor analgesia in the United States.