BACKGROUND:Black carbon (BC) is an air pollutant of growing concern due to its adverse impacts on health and climate. Growing evidence suggests that BC could have a number of negative impacts on morbidity and mortality, but more evidence is needed. OBJECTIVE:The objectives of this study are to quantify any associations between BC exposure and cause-specific (cardiovascular and cancer) mortality outcomes. METHODS:Using the Malmö Diet and Cancer Cohort linked with a high-resolution dispersion model, we examined the association between long-term exposure to locally emitted BC, nitrogen oxides (NOx) and fine particulate matter (PM2.5) with cardiovascular and cancer mortality. RESULTS:In fully adjusted models, BC exposure was consistently associated with cardiovascular mortality (HR 1.15 [1.06-1.26] per IQR increase), an association that was stronger and more robust than for PM2.5 or NOx. This association was present across all models, all time periods and both sets of exposure intervals. This association was stronger than with the other pollutants. Less clear association was found between any pollutant and cancer mortality. CONCLUSION:This study shows associations between BC exposure and especially cardiovascular mortality, consistent with international evidence showing similar impacts. For cancer mortality, there were tendencies of an association with BC but less clear than for cardiovascular mortality. These findings suggest a unique role of BC in air pollution-related cardiovascular mortality and support the need for action on mitigation of air pollution in general and BC in particular.

Abstract Background Understanding disease natural history is important for the development of potential treatments for people with MSA. We describe the natural progression of early MSA in a Chinese population. Methods Observational, 12-month study conducted in 8 sites across China . Eligible participants were aged 40–75 years, with possible or probable MSA of the parkinsonian (MSA-P) or cerebellar (MSA-C) subtype, and anticipated survival of ≥ 3 years. Disease progression was analyzed using a linear mixed model of Total UMSARS (Part I + II) progression, including baseline, Month 6 and Month 12 data. Results A total of 89 participants with a mean ± SD time since diagnosis of 0.4 ± 0.6 years were enrolled. Of these 52% had MSA-C and 48% participants had MSA-P. The mean ± SE [95%CI] rate of Total UMSARS progression was 1.27 ± 0.13 [1.01, 1.53] points per month. Participants showed a progression of 0.64 ± 0.06 [0.51, 0.76] points/month on UMSARS Part I and 0.62 ± 0.07 [0.47, 0.77] points/month on UMSARS Part II. Differences in the rates of UMSARS progression between patients with MSA-P and MSA-C were not statistically significant ( p > 0.05). Conclusions This is the first multicenter natural history study of MSA progression conducted in China. While prior studies have indicated a predominance of MSA-C in Asian populations, we found a more even split of MSA-C and MSA-P subtypes. In this early population, patients showed an average progression rate of ~ 15 Total UMSARS points/year; rates of progression were similar between the two subtypes and were in alignment with previous studies that assessed disease progression using UMSARS in Western populations. Trial registration Clinicaltrals.gov, NCT05453058 (registered June 16, 2022).

Abstract Background Exposure to particulate air pollution seem to be a contributing cause to lung cancer incidence; however, the role of the size and composition of the particles is still unclear. The objective was to assess the association between source-specific concentrations of ambient particulate air pollution and lung cancer incidence in a Swedish cohort in a low-level area. Methods Participants in the Västerbotten intervention programme cohort from Northern Sweden were recruited between January 1990 and December 2014 and followed until diagnosis for lung cancer, as defined by Swedish national hospital, cause of death and pharmaceutical registers. Exposure to total particulate matter with aerodynamic diameter ≤ 10 µm (PM10) and ≤ 2.5 µm (PM2.5) as well as source-specific PM concentrations from traffic (PM10-traffic), exhaust (PM2.5-exhaust) and wood burning (PM2.5-wood burning) was estimated at each individual’s home address using dispersion models with high spatial resolution (down to 35 x 35 m2). For the years of follow-up, the moving average of source-specific pollutants was calculated for the time windows 1–5 years (lag 1–5) and 6–10 years (lag 6–10) preceding the outcome. Cox regression models were used to assess Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) for the association between air pollution exposure and lung cancer incidence, adjusted for relevant potential confounding factors. Results The median age of the 51,064 participants was 40 years at baseline. During 421,466 person-years of follow-up, 253 incident cases of lung cancer were observed. Non-statistically significant risk increases associated with PM10, PM2.5, PM10-traffic, PM2.5-exhaust and PM10-wood burning, respectively in single-pollutant unadjusted models. The risk estimates changed considerably by adjustment for individual-level baseline covariates as well as area-level socioeconomics. The HR for incident lung cancer associated with a 1 µg/m3 increase in PM2.5-exhaust was 1.20 (95% Confidence Interval, CI: 0.65–2.23), whereas the corresponding HR associated with PM2.5-wood burning was 1.05 (95% CI: 0.70–1.57), in single-pollutant models. Conclusions There was some evidence for an association between exposure to particles from traffic, but not wood burning, and incidence of lung-cancer in this register-based study, but not for with particles from wood burning.

Background: The long-term effectiveness of vortioxetine for facilitating progress toward personal recovery goals and improving productivity at work was assessed in patients with major depressive disorder (MDD). Methods: Single-arm, prospective, 24-week cohort study in employed patients with MDD initiating treatment with vortioxetine (n = 121) in outpatient settings in Japan. The Goal Attainment Scale for Depression (GAS-D) was used to evaluate progress toward personal recovery goals. At baseline, a combination of patient-defined and pre-specified goals was established collaboratively with the treating psychiatrist, followed by longitudinal assessments at baseline and weeks 4, 8, 12, and 24. Work-related productivity was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire. Co-primary endpoints were the proportion of patients achieving their pre-specified personal recovery goals at week 12 and the change in work productivity from baseline. Results: In all, 45/107 patients (42.1%) had achieved their personal recovery goals at week 12, increasing to 62/100 (62.0%) at week 24. Significant improvement was observed across all WPAI domains (i.e., absenteeism, presenteeism, productivity loss, and activity impairment) at week 24. Depressive symptoms, global patient functioning, emotional and cognitive symptoms, cognitive performance, and quality of life also significantly improved over the 24 weeks of follow-up. At week 24, 80/102 patients (78.4%) remained on vortioxetine; 49 of these patients (61.3%) were receiving vortioxetine 20 mg/day. Limitations: Open-label study. Conclusions: Vortioxetine was found to be effective in helping to achieve personal recovery goals and in enhancing workplace productivity over the 6-month study period in patients with MDD. Trial registration: Japan Primary Registries Network: JRCT1031210200.

BACKGROUND:Presence of comorbidities can complicate the diagnosis and treatment of major depressive disorder (MDD), and often requires tailored therapeutic strategies. Primary effectiveness findings from the RELIEVE study demonstrated the effectiveness of vortioxetine treatment in improving patient function, cognitive performance, and health-related quality of life. The aim of the current sub-group analyses was to evaluate the effectiveness of vortioxetine in patients with MDD plus somatic comorbidities recorded at baseline. METHODS:RELIEVE was a 24-week observational study (NCT03555136) of outpatients with MDD starting vortioxetine in routine care. We evaluated effectiveness using patient reported outcomes in those sub-groups of patients with somatic comorbid conditions that had sufficient representation in the RELIEVE database (n ≥ 50). RESULTS:Of the 737 patients with MDD in the RELIEVE study, 428 (58.1 %) had a somatic co-morbidity and/or obesity reported in their medical records at baseline. The most common somatic conditions recorded were obesity 186 (25.2 %; defined as BMI ≥30), sleep disorders 162 (22.0 %), cardiovascular disorders 123 (16.7 %), chronic pain 63 (8.5 %), and diabetes 53 (7.2 %). Sustained clinically meaningful improvements in patient functioning as assessed by Sheehan disability scores (primary effectiveness endpoint; change from baseline to week 24 ranging from -7.1 to -9.7 points across sub-groups) were consistently observed in all comorbidity sub-groups. LIMITATIONS:The RELIEVE study was not primarily designed to investigate effectiveness of vortioxetine in patients with somatic comorbidities. CONCLUSIONS:Improvements in functioning and symptoms were observed over the 24-week period among patients with MDD and comorbid obesity, sleep disorders, cardiovascular disease, chronic pain, or diabetes, receiving vortioxetine treatment in routine practice.

Multiple system atrophy is a neurodegenerative and rapidly progressing disease. Although symptoms often overlap, diagnostic criteria define two motor phenotypes: cerebellar and Parkinsonian. Little is known about available health-economic parameters for multiple system atrophy, and it remains unclear if the current available data are sufficient to construct an early health technology assessment. This assessment considered (i) if data gaps can be minimised or cost-effectiveness modelling can be facilitated by conducting literature searches for disease analogues, (ii) if an early health technology assessment is feasible with the currently available data, and (iii) the potential for developing user-friendly model interfaces in rare diseases. Literature searches were conducted for economic evaluations and health-economic parameters (including costs, utilities, natural history of disease) for multiple system atrophy. The searches for disease analogues focussed on economic evaluations and showed a widespread use of functional or disability scales to inform model structures; we therefore used the unified multiple system atrophy rating scale part IV (global disability scale) to inform the model structure. Natural history of disease data were used to inform utilities and transition probabilities. Analyses of a hypothetical intervention were conducted from the perspective of the United Kingdom National Health Service with a cost-effectiveness threshold of £30,000 per quality-adjusted life year. The cost-effectiveness analysis was presented using a user-friendly interface in R Shiny, which provides stakeholders with an opportunity to explore results. Cost-effectiveness analyses were not identified for multiple system atrophy; however, two cost-of-illness, 20 quality-of-life, and nine natural history of disease studies were identified. Health-economic parameters were estimated from registry data, such as utilities and transition probabilities. A cost-effectiveness analysis was constructed for a hypothetical intervention despite evidence shortcomings, for example, aggregated cost data. An R Shiny app with a user-friendly interface was developed for stakeholders to change inputs and evaluate results. Literature searches for disease analogues proved useful for early modelling in multiple system atrophy, for example, to inform model structures, but surrogate data could only be used when sufficient granularity was available (e.g., micro costing). These findings suggest that early conceptual modelling can help identify data gaps and guide future evidence generation, such as selecting appropriate endpoints for natural history of disease studies. Cost-effectiveness results can be highly uncertain for rare diseases at these early stages and should be considered as part of an iterative modelling framework.

Objective: Postoperative atrial fi brillation (POAF) is a common complication after cardiac surgery that is associated with other adverse outcomes. Recent studies have shown that drainage of pericardial effusion by a posterior pericardial incision reduces the incidence of POAF. An alternative approach is a chest tube placed posteriorly in the pericardium. We evaluated whether the use of a posterior pericardial drain was associated with reduced risk of POAF in patients undergoing coronary artery bypass graft (CABG) and/or aortic valve replacement (AVR). Methods: This observational study included 2535 patients who underwent CABG (n = 1997), AVR (n = 293), or combined CABG and AVR (n = 245) in Iceland from 2002 to 2020. From our study population, 553 (22%) received a 20-Fr posterior pericardial chest tube in addition to standard mediastinal and left pleural drains. The incidence of POAF in patients with and without a posterior pericardial drain was compared before and after 1:1 propensity score matching. Results: Of 2535 patients, 1100 were included in the matched cohort. The incidence of POAF was lower in patients receiving posterior pericardial chest tube drainage compared with the control group, both before (34% vs 43%, P < .001) and after (33% vs 43%, P = .002) matching. In a multivariable analysis, posterior pericardial chest tube drainage was independently associated with a reduced risk for POAF (adjusted odds ratio 0.67; 95% confidence interval, 0.52-0.88; P = .003). Conclusions: This observational study suggested that posterior pericardial chest tube drainage is associated with a significant reduction of POAF after routine CABG and/or AVR procedures. The results are hypothesis-generating and must be confirmed in prospective randomized trials. (JTCVS Open 2024;22:244-54)

Background and Objectives There are significant challenges when obtaining clinical and economic evidence for health technology assessments of rare diseases. Many of them have been highlighted in previous systematic reviews but they have not been summarised in a comprehensive manner. For all stakeholders working with rare diseases, it is important to be aware and understand these issues. The objective of this review is to identify the main challenges for the economic evaluation of orphan drugs in rare diseases.Methods An umbrella review of systematic reviews of economic studies concerned with orphan and ultra-orphan drugs was conducted. Studies that were not systematic reviews, or on advanced therapeutic medicinal products, personalised medicines or other interventions that were not considered orphan drugs were excluded. The database searches included publications from 2010 to 2023, and were conducted in MEDLINE, EMBASE and the Cochrane library using filters for systematic reviews, and economic evaluations and models. These filters were combined with search terms for rare diseases and orphan drugs. A hand search supplemented the literature searches. The findings were reported by a compliant Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.Results Two hundred and eighty-two records were identified from the literature searches, of which 64 were duplicates, whereas five reviews were identified from the hand search. A total of 36 reviews were included after screening against inclusion/exclusion criteria, 35 from literature searches and one from hand searching. Of those studies 1, 27 and 8 were low, moderate and high quality, respectively. The reviews highlight the scarcity of evidence for health economic parameters, for example, clinical effectiveness, costs, quality of life and the natural history of disease. Health economic evaluations such as cost-effectiveness and budget-impact analyses were scarce, and generally low-to-moderate quality. The causes were limited health economic parameters, together with publications bias, especially for cost-effectiveness analyses.Conclusions The results highlighted issues around a considerable paucity of evidence for economic evaluations and few cost-effectiveness analyses, supporting the notion that a paucity of evidence makes economic evaluations of rare diseases more challenging compared with more prevalent diseases. Furthermore, we provide recommendations for more sustainable approaches in economic evaluations of rare diseases.

Background: Patients with major depressive disorder (MDD) experience depressive symptoms such as anhedonia as well as cognitive dysfunction which can subsequently impair their work performance. Purpose: To assess the effectiveness and safety of vortioxetine in working patients with MDD in South Korea. Patients and Methods: This was a subgroup analysis of a prospective, multicenter, non-interventional, non-comparative post-marketing surveillance (PMS) study. Vortioxetine-na & iuml;ve patients aged >18 years who were administered with vortioxetine were followed for up to 24 +/- 2 weeks. Working patients were defined as those who were working or studying full- (>= 6 hours/day) or part-time (<6 hours/day) at baseline. Effectiveness and adverse events (AEs), assessed by both clinician and patient-reported measured, were analyzed. Results: A total of 1082 working patients (mean age: 39.56 years) were included in the subgroup analysis. Clinically significant improvements in depressive symptoms, including anhedonia, were observed over the 24 weeks of follow-up, with mean scores for the total Montgomery-Asberg Depression Rating Scale (MADRS) and anhedonia subscale both significantly decreasing from baseline by mean +/- standard deviation (SD) of 9.73 +/- 9.08 and 5.37 +/- 5.24 points, respectively, at 24 weeks (both p<0.001 vs baseline). The vast majority of patients (80.01%) treated with vortioxetine also showed improvements in mental health symptoms over the 24 weeks, measured using the Clinical Global Impression - Improvement (CGI-I) scores. Significant improvements in cognitive symptoms were also observed over the study period, measured by the Korean Version of the Perceived Deficits Questionnaire-Depression as well as Digit Symbol Substitution Test (all p<0.0001 from baseline at Visits 2 and 3). Vortioxetine was well tolerated in working patients, with the respective rates of any AEs and serious AEs being 18.67% and 1.20%. Conclusion: Working patients treated with vortioxetine had improvements in their depressive symptoms (including anhedonia), cognitive function and performance. Vortioxetine was found to be well tolerated in this study.

ObjectiveNarrative review of the processes of goal setting and goal attainment scaling, as practical approaches to operationalizing and implementing the principles of shared decision making (SDM) in the routine care of people living with major depressive disorder (MDD).MethodsWe searched electronic databases for clinical studies published in English using key terms related to MDD and goal setting or goal attainment scaling. Two clinical studies of goal setting in MDD are considered in detail to exemplify the practicalities of the goal setting approach.ResultsWhile SDM is widely recommended for people living with mental health problems, there is general agreement that it has thus far been implemented variably. In other areas of medicine, the process of goal setting is an established way to engage the patient, facilitate motivation, and assist the recovery process. For people living with MDD, the concept of goal setting is in its infancy, and only few studies have evaluated its clinical utility. Two clinical studies of vortioxetine for MDD demonstrate the utility of goal attainment scaling as an appropriate outcome for assessing functional improvement in ways that matter to the patient.ConclusionsGoal setting is a pragmatic approach to turning the principles of SDM into realities of clinical practice and aligns with the principles of recovery that encompasses the notions of self-determination, self-management, personal growth, empowerment, and choice. Accumulating evidence supports the use of goal attainment scaling as an appropriate personalized outcome measure for use in clinical trials. Shared decision making is a structured approach in which a doctor assists their patient in making informed choices about treatment that consider the patient's own preferences. However, while acknowledged as the ideal approach, many doctors working in the mental health area say it can be difficult to apply in their daily clinical practice. In other areas of medicine, such as physical rehabilitation, the structured process of patients setting treatment goals in dialogue with their doctor has been recommended as a practical way to put the principles of shared decision making into practice.In this paper, we reviewed the medical literature to better understand how goal setting can be used to improve the care of people with major depressive disorder. The available evidence supports goal setting as a powerful way to engage patients in healthcare decisions, and ultimately improve health-related outcomes. The goal setting process provides patients the opportunity to verbalize their own, tangible goals for treatment; and following some negotiation, receive endorsement of their goals from their doctor. Patients feel supported and are better motivated to continue with their treatment.While still in its infancy, the growing evidence base supporting goal setting for people with major depressive disorder is encouraging. For example, the Goal Attainment Scaling (GAS) method of evaluating treatment success has been suitably adapted for use in people living with depression (GAS-D) and provides an easy, structured format for discussing personal treatment goals, as well as a method for tracking success, both in clinical practice and research studies.

Abstract Background To assess whether retrograde cerebral perfusion reduces neurological injury and mortality in patients undergoing surgery for acute type A aortic dissection. Methods Single-center, retrospective, observational study including all patients undergoing acute type A aortic dissection repair with deep hypothermic circulatory arrest between January 1998 and December 2022 with or without the adjunct of retrograde cerebral perfusion. 515 patients were included: 257 patients with hypothermic circulatory arrest only and 258 patients with hypothermic circulatory arrest and retrograde cerebral perfusion. The primary endpoints were clinical neurological injury, embolic lesions, and watershed lesions. Multivariable logistic regression was performed to identify independent predictors of the primary outcomes. Survival analysis was performed using Kaplan-Meier estimates. Results Clinical neurological injury and embolic lesions were less frequent in patients with retrograde cerebral perfusion (20.2% vs. 28.4%, p = 0.041 and 13.7% vs. 23.4%, p = 0.010, respectively), but there was no significant difference in the occurrence of watershed lesions (3.0% vs. 6.1%, p = 0.156). However, after multivariable logistic regression, retrograde cerebral perfusion was associated with a significant reduction of clinical neurological injury (OR: 0.60; 95% CI 0.36–0.995, p = 0.049), embolic lesions (OR: 0.55; 95% CI 0.31–0.97, p = 0.041), and watershed lesions (OR: 0.25; 95%CI 0.07–0.80, p = 0.027). There was no significant difference in 30-day mortality (12.8% vs. 11.7%, p = ns) or long-term survival between groups. Conclusion In this study, we showed that the addition of retrograde cerebral perfusion during hypothermic circulatory arrest in the setting of acute type A aortic dissection repair reduced the risk of clinical neurological injury, embolic lesions, and watershed lesions.

In this study, the long-term mortality effects associated with exposure to PM10 (particles with an aerodynamic diameter smaller than or equal to 10 µm), PM2.5 (particles with an aerodynamic diameter smaller than or equal to 2.5 µm), BC (black carbon), and NOx (nitrogen oxides) were analyzed in a cohort in southern Sweden during the period from 1991 to 2016. Participants (those residing in Malmö, Sweden, born between 1923 and 1950) were randomly recruited from 1991 to 1996. At enrollment, 30,438 participants underwent a health screening, which consisted of questionnaires about lifestyle and diet, a clinical examination, and blood sampling. Mortality data were retrieved from the Swedish National Cause of Death Register. The modeled concentrations of PM10, PM2.5, BC, and NOx at the cohort participants’ home addresses were used to assess air pollution exposure. Cox proportional hazard models were used to estimate the associations between long-term exposure to PM10, PM2.5, BC, and NOx and the time until death among the participants during the period from 1991 to 2016. The hazard ratios (HRs) associated with an interquartile range (IQR) increase in each air pollutant were calculated based on the exposure lag windows of the same year (lag0), 1–5 years (lag1–5), and 6–10 years (lag6–10). Three models were used with varying adjustments for possible confounders including both single-pollutant estimates and two-pollutant estimates. With adjustments for all covariates, the HRs for PM10, PM2.5, BC, and NOx in the single-pollutant models at lag1–5 were 1.06 (95% CI: 1.02–1.11), 1.01 (95% CI: 0.95–1.08), 1.07 (95% CI: 1.04–1.11), and 1.11 (95% CI: 1.07–1.16) per IQR increase, respectively. The HRs, in most cases, decreased with the inclusion of a larger number of covariates in the models. The most robust associations were shown for NOx, with statistically significant positive HRs in all the models. An overall conclusion is that road traffic-related pollutants had a significant association with mortality in the cohort.

In their recent publication, Kühnel et al1 described the progression of multiple system atrophy (MSA) in the European MSA study group (EMSA-SG) cohort via an innovative disease progression model (DPM). DPMs are valuable longitudinal methods to describe MSA natural history while accounting for data uncertainty (delayed diagnosis, uncertain timing, heterogeneous staging).2 The mean trajectories of clinical progression are described along the homogeneous disease continuum (Fig. 1C) rather than the observed time since diagnosis (Fig. 1A) thanks to a temporal recalibration of progression according to an individual latent disease time, anchored to MSA disease stage at inclusion. The population characteristics and the length of individual follow-up are critical in natural history studies and DPMs. Kühnel's study relied on 121 patients with rather advanced stage, outdated diagnosis criteria, and short follow-up of 2 years.1, 3 We replicated Kühnel's analysis on repeated Unified MSA Rating Scale sum scores I (activities of daily living) and II (motor examination) from the French MSA cohort4 (663 patients) with maximum follow-up of 11 years, consensus diagnosis criteria,5 and early stages at entry (see Supplementary Material Data S1 for details). MSA progression spanned a larger period than in the original paper (Fig. 1C) with mean time gaps at inclusion estimated at 3.6 and 9.1 years for moderately-dependent and helpless patients at inclusion, respectively (Fig. 1B right panels); and significant inter-patient differences (SD = 2.14 years). When restricting the sample to 2.5-year follow-up, these differences were smaller, especially among the most aggressively affected patients at entry, with estimates of 2.5 and 6.6 years (Fig. 1B left panels) and smaller inter-patient differences (SD = 0.79 years). This suggests that studies restricted to short-term follow-up overestimate the progression rate and underestimate inter-patient differences. When applying DPMs, differences across stages should be carefully interpreted. They do not quantify the expected amount of time spent in each stage by a patient, but the time gap between patients entering the study at different stages. Estimating the duration spent in each disability stage requires specific modeling of disability over time. Non-informative death: death is assumed to be predictable by the observed course of the markers when death caused by MSA may induce a more informative dropout to be jointly modeled.6 In conclusion, DPM constitutes a promising tool for disease study, but it needs to be interpreted with caution and calls for less stringent assumptions. The replication on the French MSA cohort highlights the importance of describing MSA progression based on long-term follow-up data and large cohorts to prevent too pessimistic projections and underestimation of sample sizes. We would like to thank the French National Research Agency (Project DyMES-ANR-18-C36-0004-01) and the Nouvelle-Aquitaine region (Project AAPR2021A-2020-11937310) for their financial support that made this work possible. Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases—Project ID no: 739510. T.S.: 1A, 1B, 1C, 2A, 2B, 3A M.F.: 2C, 3B A.P.L.: 2C, 3B M.L.: 2C, 3B C.H.: 2C, 3B P.P.: 2C, 3B W.G.M.: 2C, 3B O.R.: 2C, 3B A.F.S.: 1A, 1B, 2A, 2C, 3A C.P.L.: 1A, 1B, 2A, 2C, 3A Research data are not shared. Data S1. Supporting Information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Purpose: Originally developed in English, the Oxford Depression Questionnaire (ODQ) is a patient-reported scale specifically developed for assessing emotional blunting in people with major depressive disorder (MDD). We aimed to examine the reliability and validity of the Japanese version of the ODQ.Patients and methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the ODQ and other clinical rating scales at baseline and Weeks 8, 12 and 24. Results: One hundred and sixteen patients initiated vortioxetine and had >= 1 post-baseline visit. Directionally, the associations between ODQ scores and other clinical measures were as expected and demonstrated good concurrent validity. Factor analysis shows that the scale has a good fit for three factors. The Cronbach's alpha coefficient was 0.912, and the scale also showed good test-retest reliability with intraclass correlation coefficients for the ODQ total score and domains ranging between 0.69 and 0.82. ODQ scores had strong positive correlations with symptom severity assessed using the Montgomery and angstrom sberg Depression Rating Scale and were moderately correlated with work productivity, overall functioning, and quality of life scales.Conclusion: Data from this prospective analysis confirm that the Japanese version of the ODQ retains the good validity and reliability of the original English scale and is suitable for use in prospective studies wanting to capture treatment effects on emotional blunting in MDD.

Background Vortioxetine has demonstrated procognitive effects in patients with major depressive disorder (MDD). We assessed the effectiveness and safety of vortioxetine in a cohort of patients with MDD and comorbid Alzheimer’s disease participating in a large post-marketing surveillance study in South Korea. Methods Subgroup analysis of a 6-month, prospective, multicenter, non-interventional cohort study in outpatients with MDD with a pre-baseline diagnosis of Alzheimer’s disease receiving vortioxetine in routine care settings ( n = 207). Patients were assessed at baseline and after 8 weeks; a subset of patients was also assessed after 24 weeks. Depression severity was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) scale, cognitive symptoms using the Perceived Deficits Questionnaire–Depression, Korean version (PDQ-K), and cognitive performance using the Digit Symbol Substitution Test (DSST). Results Most patients were receiving a mean daily vortioxetine dose of 5 mg/day (174/190 patients; 91.6%). After 24 weeks of vortioxetine treatment, 71.4% of patients (40/56) had experienced overall clinical improvement (i.e., CGI–Improvement score ≤3) and 51.9% (28/54) had achieved remission from depressive symptoms (i.e., MADRS total score ≤10 points). Respective mean changes in MADRS, PDQ-K, and DSST total scores from baseline to week 24 were −11.5 ( p < 0.0001), −5.1 ( p = 0.03), and +3.8 points ( p = 0.0524). Adverse events were reported by 27 patients (13.0%) and were mostly mild (89.2%). Conclusion Patients with MDD and comorbid Alzheimer’s disease receiving vortioxetine in routine care settings in South Korea demonstrated clinically meaningful improvements in depressive symptoms, cognitive symptoms, and objective cognitive performance over the 6-month treatment period. Treatment with vortioxetine was well tolerated in this patient cohort, with reported adverse events consistent with the established tolerability profile of vortioxetine.

ABSTRACTBackgroundClinical Impression of Severity Index for Parkinson's Disease (CISI‐PD) is a simple tool that can easily be used in clinical practice. Few studies have investigated the relationship between health‐related quality of life and the CISI‐PD.ObjectiveTo analyze the association of CISI‐PD scores with those of generic (EQ‐5D‐5L) and Parkinson's disease (PD) disease‐specific (Parkinson's Disease Questionnaire–8 [PDQ‐8]) health‐related quality of life assessments.MethodsPersons with idiopathic PD in the Swedish Parkinson's Disease registry with simultaneous registrations of CISI‐PD and EQ‐5D‐5L and/or PDQ‐8 were included. Correlations with EQ‐5D dimensions were analyzed. The relationships between the CISI‐PD, EQ‐5D‐5L, and PDQ‐8 were estimated by linear mixed models with random intercept.ResultsIn the Swedish Parkinson's Disease registry, 3511 registrations, among 2168 persons, fulfilled the inclusion criteria. The dimensions self‐care, mobility, and usual activities correlated moderately with the CISI‐PD (rs = 0.60, rs = 0.54, rs = 0.57). Weak correlations were found for anxiety/depression and pain/discomfort (rs = 0.39, rs = 0.29) (P values < 0.001). The fitted model included the CISI‐PD, age, sex, and time since diagnosis. The CISI‐PD had a statistically significant impact on the EQ‐5D and PDQ‐8 (P values < 0.001).ConclusionsThe CISI‐PD provides a moderate correlation with the EQ‐5D and could possibly be useful as a basis for defining health states in future health economic models and serving as outcomes in managed entry agreements. Nonetheless, the limitation of capturing nonmotor symptoms of the disease remains a shortcoming of clinical instruments, including the CISI‐PD.

Dear Colleagues, We thank the authors for their thoughts on our article ‘Once after a full moon: acute type A aortic dissection (ATAAD) and lunar phases’ [1]. The relation between varying acute illnesses and calendrical, geographical and meteorological phenomena has been investigated extensively lately. In addition to the current article, we have used the NORCAAD registry to investigate the relation between ATAAD and national holidays/weekends and temperature [2, 3]. We observed that weekends and national holidays had a lower incidence of surgery for ATAAD and we found that cold (<-5 C) and warm (>21 C) temperatures seem to be associated with an increase in surgery for ATAAD. Although theoretically intriguing, we wish to be humble and transparent regarding the limited clinical implication of our findings. Hypertension is the strongest risk factor for ATAAD [4] and we believe that increased blood pressure is the common denominator for the findings in our studies. The authors suggest that large seasonal variation in daylight in the Nordic countries may be a potential confounder. However, due to the case-crossover design of the current study, individual time-invariant confounders are adjusted for by design. Control days were selected within the same month and year as the date of surgery and were matched on the day of the week. Therefore, daylight variations are unlikely to have had an effect on our results. We agree that the finding of an increased incidence of ATAAD after full moon could be both fortuitous and unexplainable and therefore sought to find an explanation beyond the lunar phases per se. For instance, Cajochen et al. [5] demonstrated that during full moon, deep sleep was reduced by 30%, time to falling asleep was 5 min longer and total sleep time was reduced by 20 min. In turn, Lusardi et al. [6] showed that sleep deprivation leads to a 5to 15-mmHg increase in systolic blood pressure and a 35% increase in urine levels of norepinephrine in hypertensive patients. Finally, the nature and strength of our findings limits the clinical relevance of the study, and the results should not be regarded as definite but as an inspiration to think beyond the obvious pathophysiological mechanisms of disease. We now realize that our curiosity is shared by others.

The Unified Multiple System Atrophy Rating Scale (UMSARS) is a commonly used semiquantitative rating scale to assess symptoms and measure disease progression in multiple system atrophy (MSA). However, it is currently incompletely understood which UMSARS items are the most sensitive to change and most relevant to the patient.