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Hitherto no therapeutic has received regulatory approval for the treatment of post-COVID-19 condition (PCC). Cognitive deficits, mood symptoms and significant reduction in health-related quality of life (HRQoL) are highly replicated and debilitating aspects of PCC. We sought to determine the impact of vortioxetine on the foregoing symptoms and HRQoL in persons living with PCC. An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years of age residing in Canada and who are experiencing symptoms of World Health Organization (WHO)-defined PCC, with a history of confirmed SARS-CoV-2 infection, was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled (487 invited: 121 ineligible and 59 eligible but declined participation; 307 cleared pre-screening stage), a total of 149 participants were randomized (1:1) to receive either vortioxetine (5–20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment (i.e. end point). The primary outcome was the change from baseline-to-end point in the Digit Symbol Substitution Test. Secondary outcomes included the effect on depressive symptoms and HRQoL, as measured by changes from baseline-to-end point on the Quick Inventory of Depressive Symptomatology 16-item and WHO Wellbeing Scale 5-item, respectively. A total of 68 (90.7%) participants randomized to vortioxetine and 73 (98.6%) participants randomized to placebo completed all 8 weeks. Between-group analysis did not show a significant difference in the overall change in cognitive function [ P = 0.361, 95% confidence interval (CI) (−0.179, 0.492)]. However, in the fully adjusted model, a significant treatment × time interaction was observed in favour of vortioxetine treatment with baseline c-reactive protein (CRP) as a moderator (P = 0.012). In addition, a significant improvement in Digit Symbol Substitution Test scores were observed in vortioxetine versus placebo treated participants in those whose baseline CRP was above the mean (P = 0.045). Moreover, significant improvement was obtained in measures of depressive symptoms [ P < 0.001, 95% CI (−4.378, −2.323)] and HRQoL [ P < 0.001, 95% CI (2.297, 4.647)] in vortioxetine-treated participants and between the treatment groups [depressive symptoms: P = 0.026, 95% CI (−2.847, −0.185); HRQoL: P = 0.004, 95% CI (0.774, 3.938)]. Although vortioxetine did not improve cognitive function in the unadjusted model, when adjusting for CRP, a significant pro-cognitive effect was observed; antidepressant effects and improvement in HRQoL in this debilitating disorder were also noted. [ABSTRACT FROM AUTHOR]

Objective To evaluate the development and implementation of clinical practice guidelines for the management of depression globally. Methods We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries. Findings We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence. Conclusion Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes. [phrase omitted] [phrase omitted] Objectif Evaluer le developpement et la mise en reuvre des directives de pratique clinique pour la gestion de la depression dans le monde. Methodes Nous avons effectue une revue systematique des directives existantes en matiere de gestion de la depression chez les adultes souffrant de troubles depressifs majeurs ou de troubles bipolaires. Pour chaque directive identifiee, nous avons verifie le degre de conformite vis-a-vis des mesures de qualite du developpement des directives (transparence des processus d'elaboration des directives et de leur financement, composition multidisciplinaire du groupe d'auteurs, revue systematique des etudes d'efficacite comparative) ainsi que de la mise en reuvre (indicateurs de qualite). Nous avons confronte les directives des pays a faible et moyen revenu avec celles des pays a haut revenu. Resultats Nous avons identifie 82 directives de pratique clinique nationales et 13 directives de pratique clinique internationales dans 83 pays et en 27 langues. Les processus d'elaboration des directives et les sources de financement etaient explicitement indiquees dans une moindre proportion chez les pays a faible et moyen revenu (8/29; 28%) par rapport aux pays a haut revenu (35/58; 60%). Le nombre de directives redigees par un groupe d'auteurs multidisciplinaire etait moins eleve dans les pays a faible et moyen revenu (2/29; 7%) que dans les pays a haut revenu (22/58; 38%). Une revue systematique de l'efficacite comparative a ete menee pour 31% (9/29) des directives dans les pays a faible et moyen revenu, contre 71% (41/58) des directives dans les pays a haut revenu. Seulement 10% (3/29) des directives emises par les pays a faible et moyen revenu et 19% (11/58) de celles emises par les pays a haut revenu comprenaient un programme d'evaluation des indicateurs de qualite ou de l'adherence aux recommandations. Conclusion La mise en reuvre des directives est mal planifiee, mal analysee et mal mesuree. Reduire les disparites de developpement et de mise en reuvre des directives dans les pays a faible et moyen revenu est une priorite. A l'avenir, ces directives devraient prevoir des strategies d'execution des recommandations, mais aussi d'evaluation de la faisabilite, de la rentabilite et de l'impact sur l'etat de sante. [phrase omitted] Objetivo Evaluar la elaboracion e implementacion de las directrices de practica clinica para el tratamiento de la depresion a nivel mundial. Metodos Se realizo una revision sistematica de las directrices existentes para el tratamiento de la depresion en adultos con trastorno depresivo mayor o bipolar. Por cada directriz identificada, se evaluo el cumplimiento de las medidas de calidad de elaboracion de directrices (como la transparencia en los procesos de elaboracion de directrices y su financiamiento, la composicion del grupo multidisciplinario de autores, la revision sistematica del estudio de eficacia comparativo) y la implementacion (como los indicadores de calidad). En este contexto, se compararon las directrices de los paises de ingresos bajos y medios con las de los paises de ingresos altos. Resultados Se identificaron las directrices de practica clinica a nivel nacional (82) y a nivel internacional (13) de 83 paises en 27 idiomas. Los procesos de elaboracion de directrices y las fuentes de financiamiento se especificaron de manera explicita en un porcentaje menor de directrices de los paises de ingresos bajos y medios (8/29; 28 %) en relacion con las de los paises de ingresos altos (35/58; 60 %). Un grupo de desarrollo multidisciplinario elaboro menos directrices (2/29; 7 %) para los paises de ingresos bajos y medios, en relacion con las de los paises de ingresos altos (22/58; 38 %). Ademas, se realizo una revision sistematica sobre la efectividad comparativa en el 31 % (9/29) de las directrices de los paises de ingresos bajos y medios, frente al 71 % (41/58) de las directrices de los paises de ingresos altos. Solo el 10 % (3/29) de las directrices de los paises de ingresos bajos y medios y el 19 % (11/58) de las directrices de los paises de ingresos altos describieron planes para evaluar los indicadores de calidad o el cumplimiento de las recomendaciones. Conclusion La implementacion de las directrices no se planifica, notifica ni evalua de manera adecuada a nivel mundial. Es prioritario reducir las desigualdades en la elaboracion y la implementacion de las directrices en los paises de ingresos bajos y medios. Las directrices que se elaboren en el futuro deberan presentar estrategias para implementar las recomendaciones y evaluar la viabilidad, la rentabilidad y el impacto en los resultados sanitarios., Introduction The rising prevalence and burden of depression worldwide disproportionately affect low- and middle-income countries. (1-4) Major depressive and bipolar disorders independently increase the risk for other chronic diseases, including [...]

Purpose Multiple endocrine neoplasia types 1 (MEN1) and 2 (MEN2) are inherited endocrine tumor syndromes caused by mutations in the MEN1 or RET genes. This study aimed to investigate clinical outcomes and molecular characteristics among children with MEN. Methods This study included eight patients from seven unrelated families. Data on clinical course, biochemical findings, and radiologic studies were collected by retrospective chart review. All diagnoses were genetically confirmed by Sanger sequencing of MEN1 in three MEN1 patients and RET in four patients with MEN2A and one patient with MEN2B. Results Three patients with MEN1 from two families presented with hypoglycemia at a mean age of 11±2.6 years. Four patients with MEN2A were genetically diagnosed at a mean of 3.0±2.2 years of age by family screening; one of them was prenatally diagnosed by chorionic villus sampling. Three patients with MEN2A underwent prophylactic thyroidectomy from 5 to 6 years of age, whereas one patient refused surgery. The patient with MEN2B presented with a tongue neuroma and medullary thyroid carcinoma at 6 years of age. Subsequently, he underwent a subtotal colectomy because of bowel perforation and submucosal ganglioneuromatosis at 18 years of age. Conclusion This study described the relatively long clinical course of pediatric MEN with a mean follow-up duration of 7.5±3.8 years. Insulinoma was the first manifestation in children with MEN1. Early diagnosis by family screening during the asymptomatic period enabled early intervention. The patient with MEN2B exhibited the most aggressive clinical course. [ABSTRACT FROM AUTHOR]