What impact did the COVID-19 pandemic have on psychosis and the delivery of early intervention psychosis services?

BACKGROUND: In Australia, the first nationwide COVID-19 lockdown occurred in March 2020 bringing challenges for early intervention psychosis (EIP) services. Limited evidence exists on the impacts of the pandemic on treatment outcomes among EIP clients. METHODS: This prospective cohort study analysed routine data from 15 headspace Early Psychosis centres in Australia. Participants were 12 to 25 years, meeting criteria for First Episode Psychosis (FEP) or Ultra High Risk of psychosis (UHR) comparing those who commenced treatment 'pre-COVID-19' (between 16th August 2018 and 15th August 2019), and 'during-COVID-19' (between 1st March 2020 and 15th September 2020). Clinical symptoms at treatment commencement were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Kessler Psychological Distress Scale (K10). with outcomes after 6 months compared between cohorts using linear mixed-effects regression, controlling for confounders. RESULTS: Of 1246 young people analysed (653 FEP, 596 UHR), significant improvements were observed with treatment in both groups (5 to 13-point reduction in BPRS score per 6-months treatment). Treatment effectiveness reduced during-COVID-19 for psychosis symptoms, with the FEP BPRS treatment effect lower by 4.3 points (95%CI: 0.5, 8.1). UHR clients had lower BPRS negative symptoms during-COVID-19 (p = 0.020). Service contacts increased during-COVID-19, with increased telehealth services (p < 0.001). CONCLUSIONS: Early intervention remained effective for FEP and UHR, despite the pandemic and transition of EIP services to virtual service delivery. Reduced treatment efficacy in FEP psychosis symptoms may indicate potential limitations of telehealth. Further research to examine longer term clinical and functional outcomes due to the pandemic is required.

Vocational functioning in young people accessing services for first-episode psychosis and ultra-high risk of psychosis: A longitudinal naturalistic cohort study.

AIMS: Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment. METHODS: This is a naturalistic sample of young people aged 12-25 with FEP (n = 1574) and UHR (n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time. RESULTS: On entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment. CONCLUSION: While there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care.

Gender differences in first episode psychosis: Some arguments to develop gender specific treatment strategies.

INTRODUCTION: Some aspects of gender differences in patients with schizophrenia spectrum disorders (SSD) have been studied, especially in cross-sectional designs and with a short-term follow-up. However, only a few studies have considered the evolution during the follow-up of SSD patients according to their gender. In this study, we explore gender differences from the time of entry in an early intervention program for psychosis, up to three years follow-up. METHODS: We conducted a prospective study including a cohort of 474 patients treated at the Treatment and Early Intervention in Psychosis (TIPP) program, 319 men and 155 women, having presented a first episode of psychosis (FEP). Data regarding premorbid and baseline sociodemographic, psychopathological and patient functioning, were collected. These data were reassessed longitudinally after 2, 6, 12, 18, 24, 30 and 36 months after entry in TIPP. RESULTS: Regarding premorbid and baseline characteristics, woman developed threshold symptoms of a FEP 1 year later than men on average. Women were more likely to be married, men were more likely to live in pension or care home facility or to be homeless. Women displayed a higher rate of history of suicide attempts and exposure to childhood trauma, while men were more likely to have a forensic history, a history of abuse of alcohol and cannabis as well as a dependency to cannabis at the time of entry in TIPP. Regarding evolution, men were more prone to violent acts and were less likely to decrease their usage of substances. The longitudinal analysis highlighted that men displayed greater negative symptoms over the entire treatment period, lower functioning after 6 months and on all assessment points after. Both genders displayed similar rate of improvement in these 3 dimensions over time. CONCLUSION: Our study confirms that there are some gender differences in the early phase of psychosis that may require differentiation of assessment and treatment to improve recovery.

How "global" is research in early intervention for psychosis? A bibliometric analysis.

INTRODUCTION: Unlike high-income countries (HICs), there are few early intervention services for psychosis in low-and middle-income countries (LAMICs). In HICs, research spurred the growth of such services. Little is known about the state of EIP research in LAMICs, which we address by examining their research output and collaborations vis-à-vis that of HICs. METHODS: We conducted a search in Scopus database for early psychosis publications in scientific journals since 1980. Data from each record, including title, author affiliation, and date, were downloaded. For HIC-LAMIC collaborations, data on first, corresponding and last authors' affiliations, and funding were manually extracted. Descriptive statistics and social network analysis were conducted. RESULTS: Globally, early psychosis publications increased from 24 in 1980 to 1297 in 2022. Of 16,942 included publications, 16.1 % had LAMIC authors. 71.3 % involved authors from a single country (regardless of income level). 21.9 % were collaborations between HICs, 6.6 % between HICs and LAMICs, and 0.2 % among LAMICs. For research conducted in LAMICs and involving HIC-LAMIC collaborations, the first, last, and corresponding authors were LAMIC-based in 71.8 %, 60.7 %, and 63.0 %, respectively. These positions were dominated (80 %) by authors from four LAMICs. 29.4 % of the HIC-LAMIC subset was funded solely by LAMIC funders, predominantly two LAMICs. CONCLUSIONS: LAMICs are starkly underrepresented in the otherwise flourishing body of early psychosis research. They have far fewer collaborations and less funding than HICs. Closing these gaps in LAMICs where most of the world's youth live is imperative to generate the local knowledge needed to strengthen early psychosis services that are known to improve outcomes.

First episode psychoses in people over-35 years old: uncovering potential actionable targets for early intervention services.

The traditional youth-oriented design of Early Intervention Services (EIS) may lead to the exclusion of patients who have their psychotic onset later in life. A retrospective study was conducted to compare first-episode psychosis (FEP) patients who accessed treatment when aged ≤ 35 years with those ≥36+. A total of 854 patients were identified among 46,222 individuals who had access to community psychiatric services from 1991 to 2021. FEP were aged 18-65, received care between 2012 and 2021 and had a diagnosis of affective or non-affective FEP. Two groups were identified (FEP diagnosed at age ≤ 35 vs ≥ 36) and compared for sociodemographic and clinical characteristics. Most patients were diagnosed when aged ≥ 36+ (61.8%). Compared to the ≤ 35 group, older patients were more likely to be women, married and diagnosed with affective psychosis, and they were less frequently hospitalized. Long-acting injectables antipsychotics (LAI) were less frequently prescribed in the ≥ 36+ group, whereas antidepressants were more frequently prescribed compared to those aged ≤ 35. In both age groups, women were less frequently prescribed LAIs compared to men. These findings highlight the need to reorient EIS to accommodate the needs of older FEP, especially women.

Early specialised treatment for bipolar disorder: Long-term follow-up from the early intervention in affective disorders (EIA) randomised controlled trial.

BACKGROUND: It is unclear whether treatment early after onset in bipolar disorder may improve the long-term illness course. The early intervention in affective disorders (EIA) randomised controlled trial found that 2-years treatment in a specialised mood disorder clinic combining evidence-based pharmacological treatment with group psychoeducation improved clinical outcomes compared with standard treatment in patients with bipolar disorder discharged after their 1st, 2nd, or 3rd hospital admission. We aimed to assess the 16 years long-term outcomes after randomisation of the participants in the EIA trial. METHODS: Data were obtained by linking nation-wide Danish population-based registers. All 158 participants of the EIA trial (Trial Registration Number NCT00253071) were followed from time of randomisation (2005-2009) to end of study (31 December 2021). The primary outcome was risk of psychiatric readmission. Secondary outcomes were total admissions and costs, medication use, intentional self-harm or suicide attempt or suicide, and socio-economic measures. RESULTS: The absolute mean risk of psychiatric readmission was 49.3% in the intervention group and 59.8% in the control group, with no statistically significant difference between the groups (b = -0.10, 95% CI: -0.26 to 0.047, p = 0.18). Compared with the control group, patients in the intervention group had numerically fewer total admission days (mean (SD) 44 (77) versus 62 (109)), lower total cost of psychiatric hospital admissions and hospital-based outpatient visits (mean (SD) 22,001 (36793) euros versus 29,822 (52671) euros) and higher use of lithium and antipsychotics, but the differences were not statistically significant. Fewer patients in the intervention group had an event of intentional self-harm or suicide attempt or suicide during follow-up (OR 0.25, 95% CI: 0.15-0.40, p < 0.001) compared with the control group and more patients in the intervention group used antiepileptics (OR 2.21, 95% CI: 1.08-4.60, p = 0.031). CONCLUSION: Analyses of very long-term outcomes of the EIA trial may potentially indicate a beneficial effect of the intervention at the long term but were likely underpowered to detect a more subtle effect and for most outcomes the differences between groups were not statistically significant.

GAPi: A description of the initiative for early psychosis intervention in Latin America and the short- to medium-term outcomes in early psychosis patients.

INTRODUCTION: Schizophrenia is a debilitating disorder that affects a significant proportion of the population and leads to impaired functionality and long-term challenges. The first episode of psychosis (FEP) is a critical intervention stage for improving long-term outcomes. The GAPi program was established in São Paulo, Brazil to provide early intervention services and evaluate biomarkers in individuals with FEP. This article delineates the objectives of the GAPi program, detailing its innovative research protocol, examining the clinical outcomes achieved, and discussing the operational challenges encountered during its initial decade of operation. METHODS: The study comprised a prospective cohort of antipsychotic-naïve individuals with first-episode psychosis aged between 16 and 35 years. Participants were recruited from a public psychiatric facility in São Paulo. Emphasizing the initiative's commitment to early intervention, clinical assessments were systematically conducted at baseline and at two months, one year, two years, and five years of treatment to capture both short- and medium-term outcomes. Various assessment tools were utilized, including structured interviews, symptom scales, the Addiction Severity Index, and functional assessments. RESULTS: A total of 232 patients were enrolled in the cohort. Among them, 65.95 % completed the 2-month follow-up. Most patients presented with schizophrenia spectrum disorders, followed by bipolar disorder and major depressive disorder with psychotic features. Treatment response rates and remission rates were evaluated at different time points, with promising outcomes observed. The program also assessed socio-demographic factors, substance use, family history, and genetic and biomarker profiles, providing valuable data for research. DISCUSSION: The GAPi program has emerged as the largest ongoing cohort of antipsychotic-naïve first-episode psychosis in Latin America, contributing to the understanding of early psychosis in low- and middle-income countries. Despite operational challenges, the program has demonstrated efficacy in reducing the duration of untreated psychosis and in improving clinical outcomes. A multidisciplinary approach, including pharmacological treatment, psychosocial interventions, and family involvement, has been instrumental in enhancing treatment adherence and long-term prognosis. CONCLUSION: The GAPi program represents a valuable model for early intervention in first-episode psychosis and provides insights into the pathophysiology, treatment, and long-term outcomes of individuals with schizophrenia and related disorders. Continued research and resource allocation are essential for addressing operational challenges and expanding early intervention services in low- and middle-income countries.

Disengagement from the Ribeirão Preto early intervention program for psychosis: A retrospective cohort study.

BACKGROUND: Treatment discontinuation within Early Intervention Services (EIS) for psychosis poses a significant challenge to achieving better outcomes in the early stages of psychotic disorders. Prevalence and predictors of early disengagement from EIS located in low- and middle-income countries (LMICs) remain poorly investigated. We aimed to examine the rates and predictors of disengagement from the Ribeirão Preto Early Intervention Program for Psychosis (Ribeirão Preto-EIP) in Brazil. METHODS: We conducted a retrospective cohort study using data from patients referred to the Ribeirão Preto-EIP between January 01, 2015, and December 31, 2018. Exclusion criteria were individuals with a single consultation, a diagnosis other than a psychotic disorder, and documented cases of death. RESULTS: Our sample comprised 234 patients, with an overall median follow-up time of 14.2 months. Early treatment disengagement was observed in 26.5 % (n=62), with a median time to disengagement of 5.25 months. Univariable analysis identified non-white skin color (HR=2.10, 95 %CI 1.26-3.49), positive THC screening (HR=2.22, 95 %CI 1.23-4.01), and substance-induced psychosis (HR=2.15, 95 %CI 1.10-4.21) as significant predictors. In multivariable analysis, only non-white skin color remained a significant predictor of early disengagement (HR=1.87, 95 %CI 1.08-3.27). CONCLUSIONS: The observed rates of early disengagement in our sample are similar to those reported in wealthy countries, but higher than previously reported for LMICs. Non-white skin color predicted early disengagement in our sample, probably due to social disadvantages. Our data highlights the need for enhanced research elucidating the specific features of EIS in LMICs.

Tracking the 3-year trajectory of referrals to an early psychosis intervention service.

AIM: To review the baseline and clinical characteristics of patients referred to a New Zealand Early Psychosis Intervention (EPI) service across a 4-year timeframe. METHOD: We compared two cohorts, and identified variables associated with being accepted or declined, and reasons for decline, by an EPI service between 2013 and 2017. RESULTS: There were 576 people with suspected psychosis referred to the EPI service for assessment: 300 (52%) were accepted, 221 (38%) declined and 55 (10%) were not processed. Reasons for being declined by EPI services were a long duration of psychosis (DUP, 48%) and no evidence of psychosis (47%). There were no significant differences between the accepted and declined group in Emergency Department presentations for self-harm or suicide attempts and acute admissions to a psychiatric inpatient unit over the 3-year follow-up period. CONCLUSION: To optimise the identification of true positive cases, EPI services require clear entry criteria. Replicating this study in other EPI services with different entry criteria may provide evidence to develop a more uniform screening process. Improved outcomes may be enhanced by measuring effectiveness and liaising with other EPI services.

Sociodemographic and clinical correlates of hallucinations in patients entering an early intervention program for first episode psychosis.

Hallucinations are a core feature of psychosis, and their severity during the acute phase of illness is associated with a range of poor outcomes. Various clinical and sociodemographic factors may predict hallucinations and other positive psychotic symptoms in first episode psychosis (FEP). Despite this, the precise factors associated with hallucinations at first presentation to an early intervention service have not been extensively researched. Through detailed interviews and chart reviews, we investigated sociodemographic and clinical predictors in 636 minimally-medicated patients who entered PEPP-Montréal, an early intervention service for FEP, between 2003 and 2018. Hallucinations were measured using the Scale for the Assessment of Positive Symptoms (SAPS), while negative symptoms were assessed using the Scale for the Assessment of Negative symptoms (SANS). Depressive symptoms were evaluated through the Calgary Depression Scale for Schizophrenia (CDSS), and anxiety symptoms via the Hamilton Rating Scale for Anxiety (HAS). A majority (n = 381, 59.9 %) of the sample presented with clinically significant hallucinations (SAPS global hallucinations score ≥ 3) at program entry. These patients had an earlier age at onset, fewer years of education, and a higher severity of delusions, depression and negative symptoms than those without clinical-level hallucinations. These results suggest that individuals with clinically significant hallucinations at admission tend to be younger and have a greater overall symptom burden. This makes it especially important to monitor hallucinations alongside delusions, depression and negative symptoms in order to identify who might benefit from targeted interventions. The implications of these findings for early intervention and person-centered care are discussed.

Ethnic density and first episode psychosis in the British Pakistani population: findings from the East Lancashire Early Intervention Service.

BACKGROUND: Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups. AIMS: To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire. METHOD: Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas. RESULTS: A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased. CONCLUSIONS: Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

Duration of Untreated Psychosis and Outcomes in First-Episode Psychosis: Systematic Review and Meta-analysis of Early Detection and Intervention Strategies.

BACKGROUND: The role of duration of untreated psychosis (DUP) as an early detection and intervention target to improve outcomes for individuals with first-episode psychosis is unknown. STUDY DESIGN: PRISMA/MOOSE-compliant systematic review to identify studies until February 1, 2023, with an intervention and a control group, reporting DUP in both groups. Random effects meta-analysis to evaluate (1) differences in DUP in early detection/intervention services vs the control group, (2) the efficacy of early detection strategies regarding eight real-world outcomes at baseline (service entry), and (3) the efficacy of early intervention strategies on ten real-world outcomes at follow-up. We conducted quality assessment, heterogeneity, publication bias, and meta-regression analyses (PROSPERO: CRD42020163640). STUDY RESULTS: From 6229 citations, 33 intervention studies were retrieved. The intervention group achieved a small DUP reduction (Hedges' g = 0.168, 95% CI = 0.055-0.283) vs the control group. The early detection group had better functioning levels (g = 0.281, 95% CI = 0.073-0.488) at baseline. Both groups did not differ regarding total psychopathology, admission rates, quality of life, positive/negative/depressive symptoms, and employment rates (P > .05). Early interventions improved quality of life (g = 0.600, 95% CI = 0.408-0.791), employment rates (g = 0.427, 95% CI = 0.135-0.718), negative symptoms (g = 0.417, 95% CI = 0.153-0.682), relapse rates (g = 0.364, 95% CI = 0.117-0.612), admissions rates (g = 0.335, 95% CI = 0.198-0.468), total psychopathology (g = 0.298, 95% CI = 0.014-0.582), depressive symptoms (g = 0.268, 95% CI = 0.008-0.528), and functioning (g = 0.180, 95% CI = 0.065-0.295) at follow-up but not positive symptoms or remission (P > .05). CONCLUSIONS: Comparing interventions targeting DUP and control groups, the impact of early detection strategies on DUP and other correlates is limited. However, the impact of early intervention was significant regarding relevant outcomes, underscoring the importance of supporting early intervention services worldwide.

Time to diagnosis of acute complications after cardiovascular implantable electronic device insertion and optimal timing of discharge within the first 24 hours.

BACKGROUND: More than 3 million cardiovascular implantable electronic devices (CIEDs) are implanted annually. There are minimal data regarding the timing of diagnosis of acute complications after implantation. It remains unclear whether patients can be safely discharged less than 24 hours postimplantation. OBJECTIVE: The purpose of this study was to determine the precise timing of acute complication diagnosis after CIED implantation and optimal timing for same-day discharge. METHODS: A retrospective cohort analysis of adults 18 years or older who underwent CIED implantation at a large urban quaternary care medical center between June 1, 2015, and March 30, 2020, was performed. Standard of care included overnight observation and chest radiography 6 and 24 hours postprocedure. Medical records were reviewed for the timing of diagnosis of acute complications. Acute complications included pneumothorax, hemothorax, pericardial effusion, lead dislodgment, and implant site hematoma requiring surgical intervention. RESULTS: A total of 2421 patients underwent implantation. Pericardial effusion or cardiac tamponade was diagnosed in 13 patients (0.53%), pneumothorax or hemothorax in 19 patients (0.78%), lead dislodgment in 11 patients (0.45%), and hematomas requiring surgical intervention in 5 patients (0.2%). Of the 48 acute complications, 43 (90%) occurred either within 6 hours or more than 24 hours after the procedure. Only 3 acute complications identified between 6 and 24 hours required intervention during the index hospitalization (0.12% of all cases). CONCLUSION: Most acute complications are diagnosed either within the first 6 hours or more than 24 hours after implantation. With rare exception, patients can be considered for discharge after 6 hours of appropriate monitoring.

The Danish OPUS Early Intervention Services for First-Episode Psychosis: A Phase 4 Prospective Cohort Study With Comparison of Randomized Trial and Real-World Data.

OBJECTIVE: The Danish OPUS trial showed significant efficacy of early intervention services for first-episode schizophrenia spectrum disorders compared with standard treatment, leading to implementation of the OPUS intervention in clinical practice. The authors sought to determine whether the effectiveness of OPUS treatment in real-world clinical practice is comparable to the efficacy seen in the trial. METHODS: The study compared patients who received OPUS treatment as part of the original randomized trial to those who received standard treatment in the trial (the control group) and those who received OPUS treatment after it was implemented in Denmark. The authors investigated whether the three groups differed on register-based outcomes, such as use of secondary health care, functional outcomes, and death. Analyses were adjusted for relevant confounders. RESULTS: Compared with trial study participants, patients who received OPUS treatment after implementation (N=3,328) had a tendency toward lower mortality (hazard ratio=0.60, 95% CI=0.33, 1.09), fewer and shorter psychiatric admissions, and possibly fewer filled prescriptions of antipsychotics and other psycholeptics after 4 or 5 years. While at first less likely to be working or studying, patients who received postimplementation OPUS treatment eventually had higher odds of working than did those in the OPUS trial (after 5 years, odds ratio=1.49, 95% CI=1.07, 2.09). The odds of being in a couple relationship were also higher among patients in the postimplementation group than those in the trial. Other outcomes showed less clear associations with treatment group. Generally, the control group in the trial fared worse than both of the OPUS treatment groups. CONCLUSIONS: Not only did OPUS treatment maintain its efficacy after it was implemented as a standard treatment, it paralleled or surpassed many of the effects observed when the OPUS intervention was delivered in a randomized trial. The study results provide further evidence in support of implementation and funding of early intervention services worldwide.

Sex differences in emergency medical services management of patients with myocardial infarction: analysis of routinely collected data for over 110,000 patients.

Emergency medical services (EMS) activation is an integral component in managing individuals with myocardial infarction (MI). EMS play a crucial role in early MI symptom recognition, prompt transport to percutaneous coronary intervention centres and timely administration of management. The objective of this study was to examine sex differences in prehospital EMS care of patients hospitalized with Ml using data from a retrospective population-based cohort study of linked health administrative data for people with a hospital diagnosis of MI in Australia (2001-18).

Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19: The TOGETHER Randomized Clinical Trial.

Importance: Data on the efficacy of hydroxychloroquine or lopinavir-ritonavir for the treatment of high-risk outpatients with COVID-19 in developing countries are needed. Objective: To determine whether hydroxychloroquine or lopinavir-ritonavir reduces hospitalization among high-risk patients with early symptomatic COVID-19 in an outpatient setting. Design, Setting, and Participants: This randomized clinical trial was conducted in Brazil. Recently symptomatic adults diagnosed with respiratory symptoms from SARS-CoV-2 infection were enrolled between June 2 and September 30, 2020. The planned sample size was 1476 patients, with interim analyses planned after 500 patients were enrolled. The trial was stopped after the interim analysis for futility with a sample size of 685 patients. Statistical analysis was performed in December 2020. Interventions: Patients were randomly assigned to hydroxychloroquine (800 mg loading dose, then 400 mg daily for 9 days), lopinavir-ritonavir (loading dose of 800 mg and 200 mg, respectively, every 12 hours followed by 400 mg and 100 mg, respectively, every 12 hours for the next 9 days), or placebo. Main Outcomes and Measures: The primary outcomes were COVID-19-associated hospitalization and death assessed at 90 days after randomization. COVID-19-associated hospitalization was analyzed with a Cox proportional hazards model. The trial included the following secondary outcomes: all-cause hospitalization, viral clearance, symptom resolution, and adverse events. Results: Of 685 participants, 632 (92.3%) self-identified as mixed-race, 377 (55.0%) were women, and the median (range) age was 53 (18-94) years. A total of 214 participants were randomized to hydroxychloroquine; 244, lopinavir-ritonavir; and 227, placebo. At first interim analysis, the data safety monitoring board recommended stopping enrollment of both hydroxychloroquine and lopinavir-ritonavir groups because of futility. The proportion of patients hospitalized for COVID-19 was 3.7% (8 participants) in the hydroxychloroquine group, 5.7% (14 participants) in the lopinavir-ritonavir group, and 4.8% (11 participants) in the placebo group. We found no significant differences between interventions for COVID-19-associated hospitalization (hydroxychloroquine: hazard ratio [HR], 0.76 [95% CI, 0.30-1.88]; lopinavir-ritonavir: HR, 1.16 [95% CI, 0.53-2.56] as well as for the secondary outcome of viral clearance through day 14 (hydroxychloroquine: odds ratio [OR], 0.91 [95% CI, 0.82-1.02]; lopinavir-ritonavir: OR, 1.04 [95% CI, 0.94-1.16]). At the end of the trial, there were 3 fatalities recorded, 1 in the placebo group and 2 in the lopinavir-ritonavir intervention group. Conclusions and Relevance: In this randomized clinical trial, neither hydroxychloroquine nor lopinavir-ritonavir showed any significant benefit for decreasing COVID-19-associated hospitalization or other secondary clinical outcomes. This trial suggests that expedient clinical trials can be implemented in low-income settings even during the COVID-19 pandemic. Trial Registration: ClinicalTrials.gov Identifier: NCT04403100.

Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial.

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.

Economic Evaluation of Extended Early Intervention Service vs Regular Care Following 2 Years of Early Intervention: Secondary Analysis of a Randomized Controlled Trial.

Cost-effectiveness studies of early intervention services (EIS) for psychosis have not included extension beyond the first 2 years. We sought to evaluate the cost-effectiveness of a 3-year extension of EIS compared to regular care (RC) from the public health care payer's perspective. Following 2 years of EIS in a university setting in Montreal, Canada, patients were randomized to a 3-year extension of EIS (n = 110) or RC (n = 110). Months of total symptom remission served as the main outcome measure. Resource use and cost data for publicly covered health care services were derived mostly from administrative systems. The incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curve were produced. Relative cost-effectiveness was estimated for those with duration of untreated psychosis (DUP) of 12 weeks or less vs longer. Extended early intervention had higher costs for psychiatrist and nonphysician interventions, but total costs were not significantly different. The ICER was $1627 per month in total remission. For the intervention to have an 80% chance of being cost-effective, the decision-maker needs to be willing to pay $5942 per month of total symptom remission. DUP ≤ 12 weeks was associated with a reduction in costs of $12 276 even if no value is placed on additional months in total remission. Extending EIS for psychosis for people, such as those included in this study, may be cost-effective if the decision-maker is willing to pay a high price for additional months of total symptom remission, though one commensurate with currently funded interventions. Cost-effectiveness was much greater for people with DUP ≤12 weeks.

Ictus vertebrobasilar: registro de tiempos de asistencia y factores relacionados con la atención precoz / Vertebrobasilar stroke: recording of care times and factors related to early care

OBJETIVO: Conocer el estado de la cadena asistencial del ictus vertebrobasilar en el área de referencia de nuestro centro hospitalario, evaluando los factores relacionados con la activación del código ictus y tiempos de actuación. PACIENTES Y MÉTODOS: Estudio observacional, analítico y retrospectivo, realizado durante el período 2017-2018, que incluye a pacientes ingresados con diagnóstico de ictus confirmado por neuroimagen. Se recogieron los datos de manera consecutiva durante su valoración en urgencias e ingreso en la unidad de ictus. Se evaluaron factores clínicos, síntomas y signos neurológicos en el momento del ingreso, detección de oclusión de gran vaso y variables relacionadas con la cadena asistencial: primera asistencia, activación de código ictus, tiempo inicio-puerta y tiempo puerta-imagen. RESULTADOS: Se incluyó a 954 pacientes, 233 con ictus vertebrobasilar. Los tiempos inicio-puerta y puerta-imagen registrados fueron significativamente mayores para el ictus de circulación posterior. Los factores relacionados con menor retraso en el tiempo inicio-puerta fueron: National Institute of Health Stroke Scale > 4, disartria y pérdida de fuerza. Se observó un menor retraso en el tiempo puerta-imagen para las variables: primera asistencia por servicio de emergencias médicas, disartria, pérdida de fuerza y presencia de más de un síntoma/signo. Fueron variables predictoras de activación del código ictus el antecedente de fumador, la clínica de disartria o pérdida de fuerza, y la presencia de más de una manifestación clínica. CONCLUSIONES: Existen dificultades en la fase prehospitalaria para identificar el ictus vertebrobasilar, lo cual origina retrasos en los tiempos de asistencia. La formación en conocimientos sobre la clínica de ictus vertebrobasilar podría permitir la optimización de esos tiempos

AIM: To determine the state of the vertebrobasilar stroke care chain in our hospital reference area by evaluating the factors related to stroke code activation and management times. PATIENTS AND METHODS: Observational, analytical and retrospective study, carried out during the period 2017-2018, which includes patients admitted with a diagnosis of stroke confirmed by neuroimaging. Data were collected consecutively during assessment in the emergency department and admission to the stroke unit. Clinical factors, neurological signs and symptoms at the time of admission, detection of large-vessel occlusion and variables related to the care chain were evaluated, namely, basic medical attention, stroke code activation, onset-to-door time and door-to-imaging time. RESULTS: Altogether 954 patients were included in the study, 233 with vertebrobasilar stroke. The onset-to-door and door-to-imaging times registered were significantly higher for posterior circulation stroke. The factors related to a lower delay in onset-to-door time were: National Institutes of Health Stroke Scale > 4, dysarthria and loss of strength. A shorter delay in door-to-imaging time was observed for the variables basic attention by medical emergency service, dysarthria, loss of strength and presence of more than one symptom/sign. Predictive variables for stroke code activation were a history of smoking, clinical signs of dysarthria or loss of strength, and the presence of more than one clinical manifestation. CONCLUSIONS: In the pre-hospital phase is is difficult to identify vertebrobasilar stroke, which causes delays in care times. Training in knowledge of the clinical features of vertebrobasilar stroke could allow these times to be optimized