Housing status and accidental substance-related acute toxicity deaths in Canada, 2016-2017. / Recherche quantitative originale Statut résidentiel et décès accidentels attribuables à une intoxication aiguë liée à une substance au Canada, 2016-2017.

INTRODUCTION: There is a complex relationship between housing status and substance use, where substance use reduces housing opportunities and being unhoused increases reasons to use substances, and the associated risks and stigma. METHODS: In this descriptive analysis of people without housing who died of accidental substance-related acute toxicity in Canada, we used death investigation data from a national chart review study of substance-related acute toxicity deaths in 2016 and 2017 to compare sociodemographic factors, health histories, circumstances of death and substances contributing to death of people who were unhoused and people not identified as unhoused, using Pearson chi-square test. The demographic distribution of people who died of acute toxicity was compared with the 2016 Nationally Coordinated Point-In-Time Count of Homelessness in Canadian Communities and the 2016 Census. RESULTS: People without housing were substantially overrepresented among those who died of acute toxicity in 2016 and 2017 (8.9% versus <1% of the overall population). The acute toxicity event leading to death of people without housing occurred more often in an outdoor setting (24%); an opioid and/or stimulant was identified as contributing to their death more frequently (68%-82%; both contributed in 59% of their deaths); and they were more frequently discharged from an institution in the month before their death (7%). CONCLUSION: We identified several potential opportunities to reduce acute toxicity deaths among people who are unhoused, including during contacts with health care and other institutions, through harm reduction supports for opioid and stimulant use, and by creating safer environments for people without housing.

Suicidality and protective factors among sexual and gender minority youth and adults in Canada: a cross-sectional, population-based study.

BACKGROUND: Sexual and gender minority populations experience elevated risks for suicidality. This study aimed to assess prevalence and disparities in non-fatal suicidality and potential protective factors related to social support and health care access among sexual and gender minority youth and adults and their heterosexual and cisgender counterparts in Canada. The second objective was to examine changes in the prevalence of suicidal ideation and protective factors during the COVID-19 pandemic. METHODS: Pooled data from the 2015, 2016 and 2019 Canadian Community Health Surveys were used to estimate pre-pandemic prevalence of suicidal ideation, plans and attempts, and protective factors. The study also estimated changes in the prevalence of recent suicidal ideation and protective factors in fall 2020, compared with the same period pre-pandemic. RESULTS: The prevalence of suicidality was higher among the sexual minority populations compared with the heterosexual population, and the prevalence was highest among the bisexual population, regardless of sex or age group. The pre-pandemic prevalence of recent suicidal ideation was 14.0% for the bisexual population, 5.2% for the gay/lesbian population, and 2.4% for the heterosexual population. The prevalence of lifetime suicide attempts was 16.6%, 8.6%, and 2.8% respectively. More than 40% of sexual minority populations aged 15-44 years had lifetime suicidal ideation; 64.3% and 36.5% of the gender minority population had lifetime suicidal ideation and suicide attempts. Sexual and gender minority populations had a lower prevalence of protective factors related to social support and health care access. The prevalence of recent suicidal ideation among sexual and gender minority populations increased in fall 2020, and they tended to experience longer wait times for immediate care needed. CONCLUSIONS: Sexual and gender minority populations had a higher prevalence of suicidality and less social support and health care access compared to the heterosexual and cisgender populations. The pandemic was associated with increased suicidal ideation and limited access to care for these groups. Public health interventions that target modifiable protective factors may help decrease suicidality and reduce health disparities.

Gender identity and sexual attraction among Canadian youth: findings from the 2019 Canadian Health Survey on Children and Youth. / Identité de genre et attirance sexuelle chez les jeunes Canadiens : résultats de l'Enquête canadienne sur la santé des enfants et des jeunes de 2019.

Gender identity and sexual attraction are important determinants of health. This study reports distributions of gender identity and sexual attraction among Canadian youth using data from the 2019 Canadian Health Survey on Children and Youth. Among youth aged 12 to 17, 0.2% are nonbinary and 0.2% are transgender. Among youth aged 15 to 17, 21.0%, comprising more females than males, report attraction not exclusive to the opposite gender. Given known associations between health and gender and sexual attraction, oversampling of sexual minority groups is recommended in future studies to obtain reliable estimates for identifying inequities and informing policy.

Gender and sexual attraction as a dimension of sexual orientation are important determinants of health among youth. Collecting gender and sexual attraction information as a routine part of public health surveillance is important for identifying inequities and informing policy. This study provides nationally representative estimates for the distribution of gender and sexual attraction among Canadian youth. This study identifies populations (nonbinary, transgender and same gender­attracted youth) that require oversampling or other approaches to ensure that reliable estimates can be obtained in public health surveillance.

Le genre et l'attirance sexuelle en tant que dimension de l'orientation sexuelle sont des déterminants importants de la santé chez les jeunes. La collecte de renseignements sur le genre et l'attirance sexuelle dans le cadre des activités habituelles de surveillance de la santé publique est importante pour relever les iniquités et orienter les politiques. Cette étude fait état d'estimations représentatives à l'échelle nationale de la répartition des genres et de l'attirance sexuelle chez les jeunes Canadiens. Cette étude répertorie les populations (non binaires, transgenres et jeunes ayant une attirance envers des personnes du même genre) devant faire l'objet d'un suréchantillonnage ou d'autres approches afin de garantir que des estimations fiables puissent être obtenues dans le cadre de la surveillance de la santé publique.

Programs and interventions promoting health equity in LGBTQ2+ populations in Canada through action on social determinants of health. / Programmes et interventions favorisant l'équité en santé dans les populations LGBTQ2+ au Canada par des mesures sur les déterminants sociaux de la santé.

Sexual and gender minorities (SGM) experience a number of health inequities. That social determinants of health drive these inequities is well-documented, but there is little evidence on the number and types of interventions across Canada that address these determinants for these populations. We conducted an environmental scan of programs in Canada that target SGM, and classified the programs based on their level of intervention (individual/interpersonal, institutional and structural). We found that few programs target women, mid-life adults, Indigenous people or ethnoracial minorities, recent immigrants and refugees, and minority language speakers, and few interventions operate at a structural level.

A number of gaps exist in programs promoting health equity and interventions by addressing social determinants of health for sexual and gender minorities in Canada. Efforts to develop new programming should consider LGBTQ2+ communities who are underserved by existing services (e.g. Indigenous people, ethnoracial minorities, women, recent immigrants or refugees). Very few programs addressed employment, disability, education or housing, which are important upstream determinants of health. Most programming focussed on the individual and interpersonal levels of intervention. Systemic interventions were scarce; efforts should focus on examining existing structural-level interventions to consider scalability.

Il existe un certain nombre de lacunes dans les programmes favorisant l'équité en santé et les interventions visant les déterminants sociaux de la santé pour les minorités sexuelles et de genre au Canada. Les efforts visant à élaborer de nouveaux programmes devraient prendre en compte les communautés LGBTQ2+, qui sont mal desservies par les services existants (en particulier les Autochtones, les minorités ethnoraciales, les femmes, les immigrants récents ou réfugiés). Très peu de programmes traitent de l'emploi, de l'invalidité, de l'éducation ou du logement, qui sont d'importants déterminants en amont de la santé. La plupart des programmes sont axés sur les niveaux d'intervention individuels et interpersonnels. Les interventions systémiques étant rares, les efforts devraient être axés sur l'étude des interventions structurelles déjà en place enfin d'en envisager l'extension.

Clinical evaluation of a new monofocal IOL with enhanced intermediate function in patients with cataract.

PURPOSE: To evaluate the effectiveness and safety of 2 enhanced monofocal intraocular lenses (IOLs). The TECNIS Eyhance IOL (Model ICB00) was compared with a standard monofocal IOL (TECNIS Monofocal, Model ZCB00). SETTING: European multicenter study. DESIGN: Prospective, bilateral, randomized, comparative/evaluator-masked, controlled study. METHODS: Adult subjects scheduled to undergo bilateral, primary phacoemulsification cataract extraction and posterior IOL implantation were randomized to receive the enhanced monofocal ICB00 IOL or the monofocal ZCB00 IOL in both eyes. Monocular endpoints at 6 months included distance-corrected intermediate visual acuity (DCIVA), photopic corrected distance visual acuity, and uncorrected intermediate visual acuity (UIVA). Binocular visual acuities, monocular corrected distance contrast sensitivity (first eyes), patient-reported outcomes, and safety were assessed at 6 months. RESULTS: Overall, 139 patients were bilaterally implanted with the enhanced monofocal IOL (n = 67) or standard monofocal IOL (n = 72) and available for the 6-month visit. The enhanced monofocal IOL significantly improved mean monocular and binocular DCIVA and UIVA by at least 1-line logarithm of the minimum angle of resolution vs the standard monofocal IOL (all P ≤ .0001). Distance vision for the enhanced monofocal IOL was 20/20 or better and comparable with that of the standard monofocal lens at 6 months. Contrast sensitivity, photic phenomena outcomes, and rates of adverse events were similar between the 2 groups. CONCLUSIONS: In patients undergoing cataract surgery, TECNIS Eyhance IOL Model ICB00 provided enhanced intermediate vision and similar distance performance and photic phenomena compared with a standard monofocal IOL, along with improved functional performance in daily life.

Clinical Evaluation of a Novel Preloaded Intraocular Lens Delivery System During Routine Cataract Surgery.

PURPOSE: To evaluate the clinical handleability and acceptability of a novel preloaded intraocular lens (IOL) delivery system for implantation of the TECNIS ZCB00 IOL (Johnson & Johnson Surgical Vision, Inc., Santa Ana, CA, USA) during routine small-incision cataract surgery. SUBJECTS AND METHODS: In this prospective, open-label, noncomparative, unilateral or bilateral, multicenter study, adult subjects with unilateral or bilateral cataracts scheduled for IOL implantation were enrolled. Surgeons and surgical technicians completed per-eye day-of-surgery and end-of-surgical-day questionnaires. The primary endpoint of the study was the rate of acceptable overall clinical performance of the preloaded IOL delivery system. Other endpoints included additional responses from the questionnaires, preimplantation incision size, and safety. RESULTS: The study included 91 eyes that underwent cataract surgery and IOL implantation using the preloaded delivery system and were available for the 1-day postoperative visit. Five surgeons and 14 surgical technicians from four investigational sites participated in the study. The rate of acceptable overall clinical performance was 100% (91/91) of eyes, with most responses (78/91; 85.7%) being the highest possible rating of 5 (very satisfied). Favorable responses by most surgeons and surgical technicians regarding additional endpoints further highlighted the handleability and acceptability of the preloaded delivery system. No ocular adverse events or lens findings (ie, no cases of IOL instability, haptic breakage, IOL marking, or crimping) were reported. CONCLUSION: The results of this study demonstrated that this preloaded IOL delivery system was safe and effective during routine small-incision cataract surgery. TRIAL REGISTRATION: German Clinical Trials Register identifier, DRKS00014757.

Clinical Comparison of the Performance of Two Marketed Ophthalmic Viscoelastic Devices (OVDs): The Bacterially Derived Healon PRO OVD and Animal-Derived Healon OVD.

This clinical investigation compared the clinical performance of two marketed ophthalmic viscoelastic devices (OVDs): the bacterially derived Healon PRO OVD (test) and the animal-derived Healon OVD (control) under normal use conditions during cataract removal and lens implantation. This prospective, multicenter, randomized, parallel, participant/evaluator masked, postmarket investigation enrolled 139 subjects (170 eyes), 116 (143 eyes) of which were treated (73 test; 70 control group). Both test and control OVDs were used, at a minimum, to inflate the anterior chamber and protect the endothelium prior to cataract extraction according to the standard procedure. The surgeon completed a postsurgery OVD clinical performance questionnaire, and intraocular pressure (IOP) was measured before surgery and at the 1 day postoperative visit with Goldmann applanation tonometry. Any IOP measurement of 30 mmHg or higher was considered a "spike" and recorded as a study-specific, serious adverse event. The bacterially derived Healon PRO OVD was found to be statistically noninferior to the overall clinical performance of the animal-derived Healon OVD control; thus, the primary hypothesis was satisfied. There were no statistically significant differences between OVD groups for any of the additional endpoints relating to IOP changes or to safety, thus satisfying additional hypotheses. The Healon PRO OVD showed statistically significant improvements in surgeon ratings for ease of injectability, transparency/visibility, and ease of IOL placement. The safety profile was also similar between OVD groups with regards to serious and/or device-related adverse events, as well as medical and lens findings. The results of this clinical investigation support the safety and effectiveness of the bacterially derived, currently marketed Healon PRO OVD and indicate that the intraocular surgical performance was similar between the two OVDs.

Clinical evaluation of a bacterially derived sodium hyaluronate 2.3% ophthalmic viscosurgical device.

PURPOSE: To compare the safety and effectiveness of bacterially derived and animal-derived sodium hyaluronate 2.3% ophthalmic viscosurgical devices (OVD) (Healon5 PRO and Healon5, respectively) in cataract surgery. SETTING: United States multicenter study. DESIGN: Prospective, randomized, masked, controlled study. METHODS: Adult patients having bilateral cataract extraction and posterior chamber intraocular lens implantation were randomly assigned to receive Healon5 PRO OVD in 1 eye (study group) and Healon5 OVD in the fellow eye (control group). The endothelial cell count (ECC) was measured preoperatively and 3 months postoperatively. Tonometry was performed preoperatively and at the 6-hour, 1-day, 1-week, 1-month, and 3-month timepoints. The cumulative rate of postoperative intraocular pressure (IOP) spikes (≥30 mm Hg) was calculated. Changes from baseline in IOP, edema, inflammation, serious adverse events, and visual acuity were also assessed. RESULTS: The study comprised 213 and 208 treated and paired-eye patients, respectively. At 3 months, there was no statistically significant difference in the mean percentage ECC change from baseline between study group and the control group (-5.55% versus -6.66%; mean difference 1.11% ± 11.89% [SD]; 95% confidence interval (CI), -0.52 to 2.74) or the cumulative IOP spike rate (8.2% versus 6.3%; mean percentage difference -1.9%; 95% CI, -5.46% to 1.61%). At 3 months, both OVD groups had significant reductions in IOP from baseline (-1.37 mm Hg and -1.32 mm Hg, respectively; both P < .0001). The distribution of edema, inflammation, serious adverse events, and visual acuity outcomes was also similar between the groups. CONCLUSION: The 2 OVDs were clinically similar in terms of safety and effectiveness for cataract surgery.

Efficacy and safety of a two-drug direct-acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4, 5 or 6.

Ruzasvir (MK-8408, an NS5A inhibitor) and uprifosbuvir (MK-3682, a nonstructural protein 5B nucleotide inhibitor) are highly potent direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection. A phase III clinical trial evaluating the two-drug combination of ruzasvir 60 mg plus uprifosbuvir 450 mg suggested suboptimal efficacy in certain HCV genotypes (C-BREEZE 1; NCT02759315). The aim of the present study was to evaluate the efficacy and safety of ruzasvir in combination with uprifosbuvir administered at a higher dose than that assessed in the earlier study (C-BREEZE 2: NCT02956629/Merck protocol PN041). Treatment-naïve or interferon (with or without ribavirin)-experienced participants with or without compensated cirrhosis were enrolled. All participants received ruzasvir 180 mg plus uprifosbuvir 450 mg once daily for 12 weeks. The primary objectives were the proportion of participants with HCV RNA <15 lU/mL at 12 weeks after the end of study therapy (SVR12), and safety and tolerability of the study drug. Overall, 282 participants were enrolled. SVR12 (n/N) was 91.3% (42/46) in participants infected with HCV genotype (GT) 1a; GT1b, 96.7% (29/30); GT2, 91.5% (43/47); GT3, 73.8% (45/61); GT4, 98.2% (55/56); GT5, 100.0% (18/18); and GT6, 90.9% (20/22). Adverse events (AEs) were reported by 61.3% of participants; drug-related AEs were reported by 33.3%. The most frequent (≥5% of participants) drug-related AEs in all participants were fatigue (7.8%) and headache (7.4%). In conclusion, the two-drug combination of ruzasvir 180 mg plus uprifosbuvir 450 mg for 12 weeks was highly effective and well tolerated in participants infected with HCV GT1, GT2, GT4, GT5 and GT6, with a lower efficacy in GT3-infected persons.

How Equity-Oriented Health Care Affects Health: Key Mechanisms and Implications for Primary Health Care Practice and Policy.

Policy Points A consensus regarding the need to orient health systems to address inequities is emerging, with much of this discussion targeting population health interventions and indicators. We know less about applying these approaches to primary health care. This study empirically demonstrates that providing more equity-oriented health care (EOHC) in primary health care, including trauma- and violence-informed, culturally safe, and contextually tailored care, predicts improved health outcomes across time for people living in marginalizing conditions. This is achieved by enhancing patients' comfort and confidence in their care and their own confidence in preventing and managing health problems. This promising new evidence suggests that equity-oriented interventions at the point of care can begin to shift inequities in health outcomes for those with the greatest need. CONTEXT: Significant attention has been directed toward addressing health inequities at the population health and systems levels, yet little progress has been made in identifying approaches to reduce health inequities through clinical care, particularly in a primary health care context. Although the provision of equity-oriented health care (EOHC) is widely assumed to lead to improvements in patients' health outcomes, little empirical evidence supports this claim. To remedy this, we tested whether more EOHC predicts more positive patient health outcomes and identified selected mediators of this relationship. METHODS: Our analysis uses longitudinal data from 395 patients recruited from 4 primary health care clinics serving people living in marginalizing conditions. The participants completed 4 structured interviews composed of self-report measures and survey questions over a 2-year period. Using path analysis techniques, we tested a hypothesized model of the process through which patients' perceptions of EOHC led to improvements in self-reported health outcomes (quality of life, chronic pain disability, and posttraumatic stress [PTSD] and depressive symptoms), including particular covariates of health outcomes (age, gender, financial strain, experiences of discrimination). FINDINGS: Over a 24-month period, higher levels of EOHC predicted greater patient comfort and confidence in the health care patients received, leading to increased confidence to prevent and manage their health problems, which, in turn, improved health outcomes (depressive symptoms, PTSD symptoms, chronic pain, and quality of life). In addition, financial strain and experiences of discrimination had significant negative effects on all health outcomes. CONCLUSIONS: This study is among the first to demonstrate empirically that providing more EOHC predicts better patient health outcomes over time. At a policy level, this research supports investments in equity-focused organizational and provider-level processes in primary health care as a means of improving patients' health, particularly for those living in marginalizing conditions. Whether these results are robust in different patient groups and across a broader range of health care contexts requires further study.

Disruption as opportunity: Impacts of an organizational health equity intervention in primary care clinics.

BACKGROUND: The health care sector has a significant role to play in fostering equity in the context of widening global social and health inequities. The purpose of this paper is to illustrate the process and impacts of implementing an organizational-level health equity intervention aimed at enhancing capacity to provide equity-oriented health care. METHODS: The theoretically-informed and evidence-based intervention known as 'EQUIP' included educational components for staff, and the integration of three key dimensions of equity-oriented care: cultural safety, trauma- and violence-informed care, and tailoring to context. The intervention was implemented at four Canadian primary health care clinics committed to serving marginalized populations including people living in poverty, those facing homelessness, and people living with high levels of trauma, including Indigenous peoples, recent immigrants and refugees. A mixed methods design was used to examine the impacts of the intervention on the clinics' organizational processes and priorities, and on staff. RESULTS: Engagement with the EQUIP intervention prompted increased awareness and confidence related to equity-oriented health care among staff. Importantly, the EQUIP intervention surfaced tensions that mirrored those in the wider community, including those related to racism, the impacts of violence and trauma, and substance use issues. Surfacing these tensions was disruptive but led to focused organizational strategies, for example: working to address structural and interpersonal racism; improving waiting room environments; and changing organizational policies and practices to support harm reduction. The impact of the intervention was enhanced by involving staff from all job categories, developing narratives about the socio-historical context of the communities and populations served, and feeding data back to the clinics about key health issues in the patient population (e.g., levels of depression, trauma symptoms, and chronic pain). However, in line with critiques of complex interventions, EQUIP may not have been maximally disruptive. Organizational characteristics (e.g., funding and leadership) and characteristics of intervention delivery (e.g., timeframe and who delivered the intervention components) shaped the process and impact. CONCLUSIONS: This analysis suggests that organizations should anticipate and plan for various types of disruptions, while maximizing opportunities for ownership of the intervention by those within the organization. Our findings further suggest that equity-oriented interventions be paced for intense delivery over a relatively short time frame, be evaluated, particularly with data that can be made available on an ongoing basis, and explicitly include a harm reduction lens.

Challenges of stroke management in resource-limited settings: A case-based reflection.

A 19-year-old man presented with a 1-year history of headache, generalised body weakness, progressive memory loss, and disorientation. One month prior to admission, there was aggravation of the weakness of the right upper limb, with new-onset difficulty with mastication, speech impairment, apathy, and urinary incontinence. On clinical examination, the patient had a motor aphasia and a right-sided hemiparesis with increased muscle tone and hyperreflexia. A noncontrast computed tomography (CT) scan of the brain revealed large ischaemic strokes extending beyond the classical vascular territories. Cerebrospinal fluid analysis showed a mildly increased protein level. The electrocardiogram revealed an irregular sinus bradycardia. The remainder of the cardiovascular and laboratory workup was unremarkable. Considering a working diagnosis of central nervous system vasculitis, the patient was treated with aspirin, prednisolone, and physiotherapy. However, he died suddenly a few weeks later. Based on this case, we discuss the challenges of stroke management in resource-limited settings, provide practical tips for general practitioners, reflect on the potential avenues for short- and long-term action, and introduce the budding collaboration platform between the University College London, the University of Liverpool, the Queen Elizabeth Central Hospital, and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.

Long-Term Follow-Up of Children Treated With Peginterferon and Ribavirin for Hepatitis C Virus Infection.

OBJECTIVES: The aim of the study was to describe the 5-year follow-up of children who received peginterferon and ribavirin in a global, open-label study. METHODS: A 5-year follow-up study of 107 children and adolescents ages 3 to 17 years with chronic hepatitis C virus infection who received peginterferon and ribavirin for 24 or 48 weeks. No drugs were administered during follow-up. RESULTS: Ninety-four patients were enrolled in the long-term follow-up portion of the study; the median duration of follow-up was 287 weeks (range, 73-339). Of 63 patients with sustained virologic response who were enrolled, 54 completed 5 years of follow-up; none had relapse in the 5-year follow-up period. Significant decreases in height z scores were observed during treatment. The effect of treatment on height z score was larger in patients treated for 48 weeks compared with those treated for 24 weeks (mean change from baseline to the end of treatment was -0.13 [P < 0.001] and -0.44 [P < 0.001] in the 24- and 48-week treatment groups, respectively). Among patients treated for 24 weeks, full recovery of height z scores to baseline was observed by 1 year of follow-up, whereas only partial recovery was observed during 5 years of follow-up in patients treated for 48 weeks (mean change from baseline to the final follow-up visit was -0.16 (P = NS) and -0.32 (P < 0.05) in the 24- and 48-week treatment groups, respectively). Similar patterns were observed for weight and body mass index z scores. CONCLUSIONS: Impairment of growth should be considered when assessing the risk-benefit profile of peginterferon/ribavirin therapy in children with hepatitis C virus infection. In deciding to treat children with chronic hepatitis C virus, considerations should include both deferring treatment in patients during optimal growth periods, and the possibility that interferon-free regimens may be available to children in the next 5 to 10 years.

Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study.

BACKGROUND: Chronic hepatitis C virus (HCV) infection in patients with stage 4-5 chronic kidney disease increases the risk of death and renal graft failure, yet patients with hepatitis C and chronic kidney disease have few treatment options. This study assesses an all-oral, ribavirin-free regimen in patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease. METHODS: In this phase 3 randomised study of safety and observational study of efficacy, patients with HCV genotype 1 infection and chronic kidney disease (stage 4-5 with or without haemodialysis dependence) were randomly assigned to receive grazoprevir (100 mg, NS3/4A protease inhibitor) and elbasvir (50 mg, NS5A inhibitor; immediate treatment group) or placebo (deferred treatment group) once daily for 12 weeks. Randomisation was done centrally with an interactive voice response system. An additional cohort of patients who were not randomised received the same regimen open-label and underwent intensive pharmacokinetic sampling. The primary efficacy outcome was a non-randomised comparison of sustained virological response at 12 weeks (SVR12) after the end of therapy for the combined immediate treatment group and the pharmacokinetic population with a historical control. The primary safety outcome was a randomised comparison between the immediate treatment group and the deferred treatment group. After 4 weeks of follow-up (study week 16), unmasking occurred and patients in the deferred treatment group received grazoprevir and elbasvir. The primary efficacy hypothesis was tested at a two-sided significance level (type I error) of 0·05 using an exact test for a binomial proportion. Safety event rates were compared between immediate treatment and deferred treatment groups using the stratified Miettinen and Nurminen method with baseline dialysis status as the strata. The study is registered at ClinicalTrials.gov, number NCT02092350. FINDINGS: 224 patients were randomly assigned to the immediate treatment group with grazoprevir and elbasvir (n=111) or the deferred treatment group (n=113), and 11 were assigned to the intensive pharmacokinetic population. Overall, 179 (76%) were haemodialysis-dependent, 122 (52%) had HCV genotype 1a infection, 189 (80%) were HCV treatment-naive, 14 (6%) were cirrhotic, and 108 (46%) were African American. Of the 122 patients receiving grazoprevir and elbasvir, six were excluded from the primary efficacy analysis for non-virological reasons (death, lost-to-follow-up [n=2], non-compliance, patient withdrawal, and withdrawal by physician for violent behaviour). No patients in the combined immediate treatment group and intensive pharmacokinetic population and five (4%) in the deferred treatment group discontinued because of an adverse event. Most common adverse events were headache, nausea, and fatigue, occurring at similar frequencies in patients receiving active and placebo drugs. SVR12 in the combined immediate treatment group and intensive pharmacokinetic population was 99% (95% CI 95·3-100·0; 115/116), with one relapse 12 weeks after end of treatment when compared with a historical control of 45%, based on meta-analyses of interferon-based regimens used in clinical trials of patients infected with HCV who are on haemodialysis. INTERPRETATION: Once-daily grazoprevir and elbasvir for 12 weeks had a low rate of adverse events and was effective in patients infected with HCV genotype 1 and stage 4-5 chronic kidney disease. FUNDING: Merck Sharp & Dohme Corp.

Safety, tolerability, and efficacy of raltegravir in a diverse cohort of HIV-infected patients: 48-week results from the REALMRK Study.

The racial diversity and gender distribution of HIV-infected patients make it essential to confirm the safety and efficacy of raltegravir in these populations. A multicenter, open-label, single-arm observational study was conducted in a diverse cohort of HIV-infected patients (goals: ≥25% women; ≥50% blacks in the United States), enrolling treatment-experienced patients failing or intolerant to current antiretroviral therapy (ART) and treatment-naive patients (limited to ≤20%). All patients received raltegravir 400 mg b.i.d. in a combination antiretroviral regimen for up to 48 weeks. A total of 206 patients received study treatment at 34 sites in the United States, Brazil, Dominican Republic, Jamaica, and South Africa: 97 (47%) were female and 153 (74%) were black [116 (56%) in the United States]. Of these, 185 patients were treatment experienced: 97 (47%) were failing and 88 (43%) were intolerant to current therapy; 21 patients (10%) were treatment naive. Among treatment-intolerant patients, 55 (63%) had HIV-1 RNA<50 copies/ml at baseline. Overall, 15% of patients discontinued: 13% of men, 18% of women, 14% of blacks, and 17% of nonblacks. At week 48, HIV RNA was <50 copies/ml in 60/94 (64%) patients failing prior therapy, 61/80 (76%) patients intolerant to prior therapy, and 16/21 (76%) treatment-naive patients. Response rates were similar for men vs. women and black vs. nonblack patients. Drug-related clinical adverse events were reported by 8% of men, 18% of women, 14% of blacks, and 9% of nonblacks. After 48 weeks of treatment in a diverse cohort of HIV-infected patients, raltegravir was generally safe and well tolerated with potent efficacy regardless of gender or race.

Chronic obstructive pulmonary disease and socioeconomic status: a systematic review.

BACKGROUND: Along with age and sex, socioeconomic status is one of the most powerful determinants of health. We conducted a systematic review to examine the consistency and magnitude of the association between socioeconomic status and COPD health outcomes to determine the potential impact of SES disparity on the COPD population. METHODS: Electronic databases to October 2011 were searched for studies of adults who had or were at risk for COPD that quantified an association between a measure of socioeconomic status and at least one COPD health outcome. Two authors independently reviewed studies, assessed study quality, and for eligible studies, extracted data. RESULTS: Regardless of the population, socioeconomic status measure or COPD outcome examined, with few exceptions, consistent significant inverse associations between socioeconomic status and COPD outcomes were found. Most studies found that individuals of the lowest socioeconomic strata were at least twice as likely to have poor outcomes as those of the highest (range from no difference to 10-fold difference). CONCLUSIONS: Social and economic disadvantage appears to have a significant consistent impact on COPD mortality and morbidity. These findings point to the need for public health strategies and research to address socioeconomic status disparity in individuals with COPD.

What is resilience?

OBJECTIVE: While everyone-including front-line clinicians-should strive to prevent the maltreatment and other severe stresses experienced by many children and adults in everyday life, psychiatrists and other health professionals also need to consider how best to support, throughout the lifespan, those people affected by severe adversity. The first step in achieving this is a clear understanding of the definitions and concepts in the rapidly growing study of resilience. Our paper reviews the definitions of resilience and the range of factors understood as contributing to it, and considers some of the implications for clinical care and public health. METHOD: This narrative review took a major Canadian report published in 2006 as its starting point. The databases, MEDLINE and PsycINFO, were searched for new relevant citations from 2006 up to July 2010 to identify key papers considering the definitions of resilience and related concepts. RESULTS: Definitions have evolved over time but fundamentally resilience is understood as referring to positive adaptation, or the ability to maintain or regain mental health, despite experiencing adversity. The personal, biological, and environmental or systemic sources of resilience and their interaction are considered. An interactive model of resilience illustrates the factors that enhance or reduce homeostasis or resilience. CONCLUSIONS: The 2 key concepts for clinical and public health work are: the dynamic nature of resilience throughout the lifespan; and the interaction of resilience in different ways with major domains of life function, including intimate relationships and attachments.

Promoting LGBT health and wellbeing through inclusive policy development.

In this paper we argue the importance of including gender and sexually diverse populations in policy development towards a more inclusive form of health promotion. We emphasize the need to address the broad health and wellbeing issues and needs of LGBT people, rather than exclusively using an illness-based focus such as HIV/AIDS. We critically examine the limitations of population health, the social determinants of health (SDOH), and public health goals, in light of the lack of recognition of gender and sexually diverse individuals and communities. By first acknowledging the unique health and social care needs of LGBT people, then employing anti-oppressive, critical and intersectional analyses we offer recommendations for how to make population health perspectives, public health goals, and the design of public health promotion policy more inclusive of gender and sexual diversity. In health promotion research and practice, representation matters. It matters which populations are being targeted for health promotion interventions and for what purposes, and it matters which populations are being overlooked. In Canada, current health promotion policy is informed by population health and social determinants of health (SDOH) perspectives, as demonstrated by Public Health Goals for Canada. With Canada's multicultural makeup comes the challenge of ensuring that diverse populations are equitably and effectively recognized in public health and health promotion policy.

The role of secreted aspartyl proteinases in Candida albicans keratitis.

PURPOSE: To evaluate virulence in a murine keratitis model using Candida albicans homozygous mutants deficient in one or more secreted aspartyl proteinases encoded by SAP genes or in transcriptional factors encoded by EFG1 and CPH1 genes. METHODS: Corneas of BALB/c mice were scarified and topically inoculated with 10(6) colony-forming units of a C. albicans human isolate (SC5314), triple SAP-null mutants (SAP1-3(-/-) and SAP4-6(-/-)), double mutants (SAP4/5(-/-), SAP4/6(-/-), SAP5/6(-/-), and SAP9/10(-/-) and EFG1(-/-)/CPH1(-/-)), single mutants (SAP4(-/-), SAP5(-/-) and SAP6(-/-), EFG1(-/-), and CPH1(-/-)), SAP6 rescuant, or parental controls (CAF2-1 and CAI-4). Animals were evaluated daily for up to 8 days after inoculation. RESULTS: Wild-type C. albicans induced severe, sustained ulcerative keratitis, and the fungal strains (CAF2-1 and CAI-4) used to generate mutants had similar corneal pathogenicity. SAP1-3(-/-), SAP4/5(-/-), and SAP9/10(-/-) mutants produced moderate keratitis similar to the virulent parental strain. SAP4-6(-/-), SAP4/6(-/-), and SAP5/6(-/-) gave rise to significantly less severe corneal inflammation. The SAP6(-/-) single mutant resulted in mild nonulcerative keratitis that resolved spontaneously within 5 days, and the SAP6 rescuant reestablished moderate disease severity. The EFG1(-/-)/CPH1(-/-) and EFG1(-/-) mutants had reduced corneal virulence, but the CPH1(-/-) strain resulted in persistent keratitis similar to control corneas. CONCLUSIONS: The EFG1-regulated SAP6 gene of C. albicans encodes a unique secreted aspartyl proteinase that contributes to corneal pathogenicity. The role of SAP6 during corneal infection appears to be associated with the morphogenic transformation of C. albicans yeasts into invasive filamentous forms.