Permanent work disability before and after ischaemic heart disease or stroke event : a nationwide population-based cohort study in Sweden

Objectives We examined the risk of disability pension before and after ischaemic heart disease (IHD) or stroke event, the burden of stroke compared with IHD and which factors predicted disability pension after either event. Design A population-based cohort study with follow-up 5 years before and after the event. Register data were analysed with general linear modelling with binary and Poisson distributions including interaction tests for event type (IHD/stroke). Setting and participants All people living in Sweden, aged 25-60 years at the first event year, who had been living in Sweden for 5 years before the event and had no indication of IHD or stroke prior to the index event in 2006-2008 were included, except for cases in which death occurred within 30 days of the event. People with both IHD and stroke were excluded, resulting in 18 480 cases of IHD (65%) and 9750 stroke cases (35%). Primary outcome measures Disability pension. Results Of those going to suffer IHD or stroke event, 25% were already on disability pension a year before the event. The adjusted OR for disability pension at first postevent year was 2.64-fold (95% CI 2.25 to 3.11) for people with stroke compared with IHD. Economic inactivity predicted disability pension regardless of event type (OR=3.40; 95% CI 2.85 to 4.04). Comorbid mental disorder was associated with the greatest risk (OR=3.60; 95% CI 2.69 to 4.83) after an IHD event. Regarding stroke, medical procedure, a proxy for event severity, was the largest contributor (OR=2.27, 95% CI 1.43 to 3.60). Conclusions While IHD event was more common, stroke involved more permanent work disability. Demographic, socioeconomic and comorbidity-related factors were associated with disability pension both before and after the event. The results help occupational and other healthcare professionals to identify vulnerable groups at risk for permanent labour market exclusion after such an event.Peer reviewe

Work disability before and after a major cardiovascular event : a ten-year study using nationwide medical and insurance registers

We examined the trajectories of work disability before and after IHD and stroke events. New IHD (n = 13521) and stroke (n = 7162) cases in 2006-2008 were retrieved from nationwide Swedish hospital records and their annual work disability days five years before and after the date of diagnosis were retrieved from a nationwide disability register. There was no pre-event differences in disability days between the IHD and stroke cases and five years prior to the event, they were close to those observed in the general population. In the first post-event year, the adjusted mean days increased to 83.9 (95% CI 80.6-86.5) in IHD; to 179.5 (95% CI 172.4-186.8) in stroke, a six-fold increase in IHD and 14-fold in stroke. Work disability leveled off among the IHD cases but not among those who had stroke. The highest disability levels for the fifth post-event year after a stroke event was associated with preexisting diabetes (146.9), mental disorder (141.2), non-employment (137.0), and immigrant status (117.9). In a working-age population, the increase in work disability after a cardiovascular event decreases close to the pre-event level in IHD but remains particularly high after stroke; among patients with comorbid depression or diabetes, immigrants, and those not in employment.Peer reviewe

The eukaryotic leading and lagging strand DNA polymerases are loaded onto primer-ends via separate mechanisms but have comparable processivity in the presence of PCNA

Saccharomyces cerevisiae DNA polymerase δ (Pol δ) and DNA polymerase ε (Pol ε) are replicative DNA polymerases at the replication fork. Both enzymes are stimulated by PCNA, although to different levels. To understand why and to explore the interaction with PCNA, we compared Pol δ and Pol ε in physical interactions with PCNA and nucleic acids (with or without RPA), and in functional assays measuring activity and processivity. Using surface plasmon resonance technique, we show that Pol ε has a high affinity for DNA, but a low affinity for PCNA. In contrast, Pol δ has a low affinity for DNA and a high affinity for PCNA. The true processivity of Pol δ and Pol ε was measured for the first time in the presence of RPA, PCNA and RFC on single-stranded DNA. Remarkably, in the presence of PCNA, the processivity of Pol δ and Pol ε on RPA-coated DNA is comparable. Finally, more PCNA molecules were found on the template after it was replicated by Pol ε when compared to Pol δ. We conclude that Pol ε and Pol δ exhibit comparable processivity, but are loaded on the primer-end via different mechanisms

Pulmonary Epithelial Integrity in Children: Relationship to Ambient Ozone Exposure and Swimming Pool Attendance

Airway irritants such as ozone are known to impair lung function and induce airway inflammation. Clara cell protein (CC16) is a small anti-inflammatory protein secreted by the nonciliated bronchiolar Clara cells. CC16 in serum has been proposed as a noninvasive and sensitive marker of lung epithelial injury. In this study, we used lung function and serum CC16 concentration to examine the pulmonary responses to ambient O(3) exposure and swimming pool attendance. The measurements were made on 57 children 10–11 years of age before and after outdoor exercise for 2 hr. Individual O(3) exposure was estimated as the total exposure dose between 0700 hr until the second blood sample was obtained (mean O(3) concentration/m(3) × hours). The maximal 1-hr value was 118 μg/m(3) (59 ppb), and the individual exposure dose ranged between 352 and 914 μg/m(3)hr. These O(3) levels did not cause any significant changes in mean serum CC16 concentrations before or after outdoor exercise, nor was any decrease in lung function detected. However, children who regularly visited chlorinated indoor swimming pools had significantly lower CC16 levels in serum than did nonswimming children both before and after exercise (respectively, 57 ± 2.4 and 53 ± 1.7 μg/L vs. 8.2 ± 2.8 and 8.0 ± 2.6 μg/L; p < 0.002). These results indicate that repeated exposure to chlorination by-products in the air of indoor swimming pools has adverse effects on the Clara cell function in children. A possible relation between such damage to Clara cells and pulmonary morbidity (e.g., asthma) should be further investigated

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) might theoretically reduce post‐stroke disability by direct effects on the brain. This Cochrane Review was first published in 2012 and last updated in 2019. OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 7 January 2021), Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, 7 January 2021), MEDLINE (1946 to 7 January 2021), Embase (1974 to 7 January 2021), CINAHL (1982 to 7 January 2021), PsycINFO (1985 to 7 January 2021), and AMED (1985 to 7 January 2021). PsycBITE had previously been searched (16 July 2018). We searched clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) recruiting stroke survivors within the first year. The intervention was any SSRI, at any dose, for any period, and for any indication. The comparator was usual care or placebo. Studies reporting at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, cognition, healthcare cost, death, adverse events and leaving the study early) were included in the meta‐analysis. The primary analysis included studies at low risk of bias. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, stroke type and, our pre‐specified outcomes, and bias sources. Two review authors independently extracted data. We used mean difference (MD) or standardised mean differences (SMDs) for continuous variables, and risk ratios (RRs) for dichotomous variables, with 95% confidence intervals (CIs). We assessed bias risks and applied GRADE criteria. MAIN RESULTS: We identified 76 eligible studies (13,029 participants); 75 provided data at end of treatment, and of these two provided data at follow‐up. Thirty‐eight required participants to have depression to enter. The duration, drug, and dose varied. Six studies were at low risk of bias across all domains; all six studies did not need participants to have depression to enter, and all used fluoxetine. Of these six studies, there was little to no difference in disability between groups SMD ‐0.0; 95% CI ‐0.05 to 0.05; 5 studies, 5436 participants, high‐quality evidence) or in independence (RR 0.98; 95% CI 0.93 to 1.03; 5 studies, 5926 participants; high‐quality evidence) at the end of treatment. In the studies at low risk of bias across all domains, SSRIs slightly reduced the average depression score (SMD 0.14 lower, 95% CI 0.19 lower to 0.08 lower; 4 studies; 5356 participants, high‐quality evidence) and there was a slight reduction in the proportion with depression (RR 0.75, 95% CI 0.65 to 0.86; 3 studies, 5907 participants, high‐quality evidence). Cognition was slightly better in the control group (MD ‐1.22, 95% CI ‐2.37 to ‐0.07; 4 studies, 5373 participants, moderate‐quality evidence). Only one study (n = 30) reported neurological deficit score (SMD ‐0.39, 95% CI ‐1.12 to 0.33; low‐quality evidence). SSRIs resulted in little to no difference in motor deficit (SMD 0.03, ‐0.02 to 0.08; 6 studies, 5518 participants, moderate‐quality evidence). SSRIs slightly increased the proportion leaving the study early (RR 1.57, 95% CI 1.03 to 2.40; 6 studies, 6090 participants, high‐quality evidence). SSRIs slightly increased the outcome of a seizure (RR 1.40, 95% CI 1.00 to 1.98; 6 studies, 6080 participants, moderate‐quality evidence) and a bone fracture (RR 2.35, 95% CI 1.62 to 3.41; 6 studies, 6080 participants, high‐quality evidence). One study at low risk of bias across all domains reported gastrointestinal side effects (RR 1.71, 95% CI 0.33, to 8.83; 1 study, 30 participants). There was no difference in the total number of deaths between SSRI and placebo (RR 1.01, 95% CI 0.82 to 1.24; 6 studies, 6090 participants, moderate quality evidence). SSRIs probably result in little to no difference in fatigue (MD ‐0.06; 95% CI ‐1.24 to 1.11; 4 studies, 5524 participants, moderate‐quality of evidence), nor in quality of life (MD 0.00; 95% CI ‐0.02 to 0.02, 3 studies, 5482 participants, high‐quality evidence). When all studies, irrespective of risk of bias, were included, SSRIs reduced disability scores but not the proportion independent. There was insufficient data to perform a meta‐analysis of outcomes at end of follow‐up. Several small ongoing studies are unlikely to alter conclusions. AUTHORS' CONCLUSIONS: There is high‐quality evidence that SSRIs do not make a difference to disability or independence after stroke compared to placebo or usual care, reduced the risk of future depression, increased bone fractures and probably increased seizure risk

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up lschaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding. Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CON-SORT) statement and provides clear and open reporting. Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.Peer reviewe

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up lschaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding. Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CON-SORT) statement and provides clear and open reporting. Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.Peer reviewe

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit