Adherence to antidepressant medications is associated with reduced premature mortality in patients with cancer: A nationwide cohort study

Background: Depression and anxiety are common in cancer and antidepressants (AD) are efficacious treatment. The relationship between AD adherence and mortality in cancer is unclear. This study aimed to evaluate the association between adherence to AD and all‐cause mortality in a population‐based cohort of patients with cancer. Materials and Methods: We conducted a 4‐year historical prospective cohort study including 42,075 patients with cancer who purchased AD at least once during the study period. Adherence to AD was modeled as nonadherence (<20%), poor (20–50%), moderate (50–80%), and good (>80%) adherence. We conducted multivariable survival analyses adjusted for demographic and clinical variables that may affect mortality. Results: During 1,051,489 person‐years at risk follow‐up, the adjusted hazard ratios (HR) for mortality were 0.89 (95% confidence interval [CI]: 0.83–0.95), 0.77 (95% CI: 0.66–0.72), and 0.80 (95% CI: 0.76–0.85) for the poor, moderate, and good adherence groups, respectively, compared to the nonadherent group. Analysis of the entire sample and a subgroup with depression, for cancer subtypes, revealed similar patterns for breast, colon, lung, and prostate cancers, but not for melanoma patients. Multivariate predictors of premature mortality included male gender (HR 1.48 [95% CI: 1.42–1.55]), current/past smoking status (HR 1.1, [95% CI: 1.04–1.15]; P < .0001), low socioeconomic status (HR 1.1, [95% CI: 1.03–1.17]; P < .0001) and more physical comorbidities. Conclusions: The present study is the first to demonstrate that higher adherence to AD is associated with a decrease of all‐cause mortality in a large nationwide cohort of cancer patients. Our data add to the pressing need to encourage adherence to AD among cancer patients.     

The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke

Wijnhoud AD, Koudstaal PJ, Dippel DWJ. The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke.
Acta Neurol Scand: 2011: 124: 238–244.
© 2011 John Wiley & Sons A/S. Background – Increased flow velocities, and combinations of low mean flow velocity (MFV) and a high pulsatility index (PI) are associated with intracranial arterial disease. We investigated the association of MFV and the ratio of PI and MFV (PI–MFV ratio) in the middle cerebral artery (MCA) with recurrence of vascular events in patients with a transient ischemic attack (TIA) or minor ischemic stroke. Methods – Five hundred and ninety‐eight consecutive patients underwent TCD investigation. Outcome events were fatal or non‐fatal stroke and the composite of stroke, myocardial infarction, or vascular death (major vascular events). Hazard ratios (HR) were estimated with Cox proportional hazards multiple regression method, adjusted for age, gender, and vascular risk factors. Results – TCD registration was successful in 489 patients. Mean follow‐up was 2.1 years. Cumulative incidence was 9% for all stroke and 12% for major vascular events. MFV over 60.5 cm/s increased the risk for both stroke (HR 2.8; 95% CI: 1.3–6.0) and major vascular events (HR 2.6; 95% CI: 1.3–5.0). Each unit increase in PI–MFV ratio was associated with a HR 2.8 (95% CI: 1.7–4.8) for stroke and HR 2.2 (95% CI: 1.3–3.6) for major vascular events. Conclusion – In patients with a TIA or non‐disabling ischemic stroke, MFV and the PI–MFV ratio in the MCA are independent prognostic factors for recurrent vascular events.     

Cardiovascular and mortality risks in Parkinson's disease patients treated with entacapone

The controlled trial Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE‐PD) reported an unexpected increase in acute myocardial infarction (AMI) with entacapone use in patients with Parkinson's disease (PD). The authors investigated whether entacapone increased cardiovascular and mortality risk compared with the use of a non‐levodopa dopamine agonist (DA) or a selective monoamine oxidase type‐B inhibitor (MAOBI). Using national Medicare data, a new‐user cohort of elderly patients with PD treated with entacapone was propensity score (PS) matched with new users of either DA or MAOBI. The PS model included variables for sociodemographics, cardiovascular disease, medications, prior PD treatment, and comorbidities. Cox proportional hazards regression was used to compare on‐therapy time to event for AMI, stroke, and death with DA‐MAOBI as a reference. Study cohorts included 8681 entacapone‐treated and 17,362 DA‐MAOBI‐treated initators who were followed for 2569 and 5385 person‐years, respectively. Cohorts were closely balanced for all covariates. During follow‐up, there were 106 AMIs, 89 strokes, and 201 deaths. The hazard ratio (HR) and 95% confidence interval (CI) associated with entacapone use was 0.86 (95% CI, 0.57–1.30) for AMI, 0.85 (95% CI, 0.54–1.35) for stroke, and 0.79 (95% CI, 0.58–1.07) for death. The risk was unchanged for treatment of≤6 months’ and>6 months’ duration and was unaffected by adjustment for time‐varying levodopa use during follow‐up. The risk of each endpoint was not differentially affected by diabetes, ischemic heart disease, or kidney failure status. However, the risk of stroke was modified by the presence (HR, 2.09; 95% CI, 0.98–4.45) or absence (HR, 0.51; 95% CI, 0.27–0.95) of advanced PD‐related morbidities (P value for interaction=0.004). Entacapone was not associated with an increased risk of AMI, stroke, or death in elderly patients with PD. © 2013 Movement Disorder Society     

Underweight predicts poststroke cardiovascular events in patients without atrial fibrillation

Background and purposeThe purpose of this study was to determine whether underweight is associated with poststroke cardiovascular events and whether such association is different according to the presence of atrial fibrillation (AF).MethodsPatients with acute stroke or transient ischemic attack who were prospectively registered in a multicenter stroke database from April 2008 to July 2020 were analyzed, excluding those aged 75 or older and those who were overweight. We prospectively captured major adverse cardiovascular events (MACE) within one year after stroke. Cox-proportional hazard regression analysis was conducted for each subgroup with or without AF after adjusting for predetermined vascular risk factors and potential confounders.ResultsAmong 30,912 patients, 1494 (4.8%) cases were underweight and 29,418 (95.2%) cases were normal weight. The cumulative event rate of 1-year MACE was higher in the underweight group (9.0%) than in the normal weight group (5.6%). In Cox-proportional regression, underweight was associated with significantly higher MACE (adjusted hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.26–2.09) and recurrent stroke (adjusted HR: 1.42, 95% CI: 1.02–1.98) in all study patients. In patients with AF, the risk of MACE for the underweight group was not significantly increased. In contrast, in patients without AF, the underweight group had a consistently higher risk of MACE (adjusted HR: 1.66, 95% CI: 1.25–2.22) and recurrent stroke (adjusted HR: 1.50, 95% CI: 1.05–2.14).ConclusionsUnderweight increased the risk of MACE and recurrent stroke within one year after acute stroke, especially in stroke without AF.     

Gender differences in bipolar disorder type I and II

Objective: We investigated gender differences in bipolar disorder (BD) type I and II in a representative cohort of secondary care psychiatric in‐ and out‐patients. Method: In the prospective, naturalistic Jorvi Bipolar Study of 191 secondary care psychiatric in‐ and out‐patients, 160 patients (85.1%) could be followed up for 18 months with a life chart. Results: After adjusting for confounders, no marked differences in illness‐related characteristics were found. However, female patients with BD had more lifetime comorbid eating disorders (P < 0.001, OR = 5.99, 95% CI 2.12–16.93) but less substance use disorders (P < 0.001, OR = 0.29, 95% CI 0.16–0.56) than males. Median time to recurrence after remission was 3.1 months longer among men than women, female gender carrying a higher hazard of recurrence (P = 0.006, HR = 2.00, 95% CI 1.22–3.27). Conclusion: Men and women with type I and II BD have fairly similar illness‐related clinical characteristics, but their profile of comorbid disorders may differ significantly, particularly regarding substance use and eating disorders. In medium‐term follow‐up, females appear to have a higher hazard of recurrence than males.     

Ginsenoside-Rd improves outcome of acute ischaemic stroke - a randomized, double-blind, placebo-controlled, multicenter trial

Background and purpose: Ginsenoside‐Rd is a receptor‐operated calcium channel antagonist and has shown promise as a neuroprotectant in our phase II study. As an extended work, we sought to confirm its efficacy and safety of Ginsenoside‐Rd in patients with acute ischaemic stroke. Methods: We conducted a randomized, double‐blind, placebo‐controlled trial involving 390 patients with acute ischaemic stroke in a 3:1 ratio to receive a 14‐day intravenous infusion of Ginsenoside‐Rd or placebo within 72 h after the onset of stroke. Our primary end‐point was the distribution of disability scores on the modified Rankin scale (mRs) at 90 days. Results: The efficacy analysis was based on 386 patients (Ginsenoside‐Rd group: 290; placebo group: 96). Ginsenoside‐Rd significantly improved the overall distribution of scores on the mRs, as compared with the placebo (P = 0.02; odds ratios [OR], 1.74; 95% confidence interval [CI], 1.08–2.78). There were significant differences between the two groups when we categorized the scores into 0–1 vs. 2–5 (P = 0.01; OR, 2.32; 95% CI, 1.23–4.38; 66.8% vs. 53.1%). It also improved the National Institutes of Health Stroke Scale (NIHSS) at 15 days [P < 0.01; least squares mean (LSM), ?0.77; 95% CI, ?1.31 to ?0.24]. Mortality and rates of adverse events were similar in the two groups. Conclusions: Ginsenoside‐Rd improved the primary outcome of acute ischaemic stroke and had an acceptable adverse‐event profile.     

Cancer risk in people with epilepsy using valproate-sodium

Singh G, Bell GS, Hernáiz‐Driever P, Sander JW. Cancer risk in people with epilepsy using valproate‐sodium.
Acta Neurol Scand: 2012: 125: 234–240.
© 2011 John Wiley & Sons A/S. Objectives – Based on reports of antitumour properties of sodium‐valproate, we hypothesised that valproate has a cancer‐protective effect in people with epilepsy. We aimed to determine cancer risk in people with epilepsy using sodium‐valproate. Materials and methods – Continuous data for 2997 people with epilepsy who had been prescribed valproate for at least two years, and for 11,988 unexposed people were provided by the UK General Practice Research Database. Hazard ratios (HRs) for all cancers and individual cancers between the exposed and unexposed groups, with smoking and alcohol consumption and age as covariates, were calculated using the Cox proportional hazards method. Results – Exposure to valproate had no influence on the incidence of the composite of all cancers [HR: 1.19, 95% CI: 0.97–1.47, P = 0.10]; there was, however, a significant excess of colon cancers [HR: 3.95, 95% CI: 1.97–7.92, P = 0.001] and a trend towards an excess of prostate neoplasms [HR: 2.15, 95% CI: 0.92–5.02, P = 0.08] and in addition, a trend towards reduced incidence of breast cancer [HR: 0.40, 95% CI: 0.14–1.30, P = 0.08] in the exposed group. Conclusions – The lack of an inverse association between valproate use and hazard ratios for all cancers and several individual cancer sites does not lend support for a cancer‐protective role for valproate.     

High‐Sensitivity C‐Reactive Protein is a Strong Risk Factor for Death after Acute Ischemic Stroke among Chinese

Background and purpose: Elevated plasma C‐reactive protein (CRP) has been suggested as a risk factor for ischemic stroke (IS) and coronary ischemic disease. Evidence has shown that high‐sensitivity CRP (hs‐CRP) is related to a worsening prognosis after IS, but hs‐CRP was rare in a large‐sample study in a Chinese population. We investigated the associations between hs‐CRP and outcome of Chinese patients after acute IS. Methods: Seven hundred and forty‐one consecutive acute IS patients (74.9% male, mean age 60.9 years), with baseline characteristics and hs‐CRP measured within 24 h after hospitalization, were admitted in this study. We also prospectively followed up for clinical outcome and death 3 months after disease onset. hs‐CRP was divided into two categories: hs‐CRP >3 mg/L and hs‐CRP ≤3 mg/L. Survival analysis using multivariable Cox regression was performed to analyze the association between hs‐CRP and stroke outcomes after adjusting for potential confounding factors. Results: Compared with low hs‐CRP, patients with high hs‐CRP (>3 mg/L) had a significantly higher rate of all‐cause death (0.71% vs. 10.00%; P < 0.001) at 3 months after stroke onset. High hs‐CRP was an independent risk factor for all‐cause death (HR, 6.48; 95% CI, 1.41 to 29.8; P= 0.016), as well as history of atrial fibrillation (HR, 5.24; 95% CI, 1.83 to 15.0; P= 0.002), no statin therapy during hospitalization (HR, 4.56; 95% CI, 2.18 to 9.55; P < 0.001), high homocysteine (>15.1 mmol/L) (HR, 2.66; 95% CI, 1.26 to 5.60; P= 0.01); fasting glucose (>6.1 mmol/L) (HR, 9.14; 95% CI, 3.34 to 25.0; P < 0.001), NIHSS at admission (HR, 2.35; 95% CI, 1.35 to 4.09; P= 0.003) and history of coronary heart disease (CHD) (HR, 2.34; 95% CI, 1.06 to 5.17; P= 0.035). Kaplan–Meier survival curves showed a higher risk of death for patients with hs‐CRP >3 mg/L (P= 0.016). Conclusion: Elevated plasma hs‐CRP independently predicted risk of all‐cause death within 3 months after acute IS in Chinese patients.     

Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP)

Thomas SHL, Drici MD, Hall GC, Crocq MA, Everitt B, Lader MH, Le Jeunne C, Naber D, Priori S, Sturkenboom M, Thibaut F, Peuskens J, Mittoux A, Tanghøj P, Toumi M, Moore ND, Mann RD. Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP) Objective: To explore whether sertindole increases all‐cause mortality or cardiac events requiring hospitalization, compared with risperidone. Method: Multinational randomized, open‐label, parallel‐group study, with blinded classification of outcomes, in 9858 patients with schizophrenia. Results: After 14147 person‐years, there was no effect of treatment on overall mortality (sertindole 64, risperidone 61 deaths, Hazard Ratio (HR) = 1.12 (90% CI: 0.83, 1.50)) or cardiac events requiring hospitalization [sertindole 10, risperidone 6, HR = 1.73 (95% CI: 0.63, 4.78)]: Of these, four were considered arrhythmia‐related (three sertindole, one risperidone). Cardiac mortality was higher with sertindole (Independent Safety Committee (ISC): 31 vs. 12, HR=2.84 (95% CI: 1.45, 5.55), P = 0.0022; Investigators 17 vs. 8, HR=2.13 (95% CI: 0.91, 4.98), P = 0.081). There was no significant difference in completed suicide, but fewer sertindole recipients attempted suicide (ISC: 68 vs. 78, HR=0.93 (95% CI: 0.66, 1.29), P = 0.65; Investigators: 43 vs. 65, HR=0.67 (95% CI: 0.45, 0.99), P = 0.044). Conclusion: Sertindole did not increase all‐cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole.     

Clinical outcome of stable outpatients with coronary, cerebrovascular or peripheral artery disease, and atrial fibrillation

BACKGROUND: The influence of atrial fibrillation (AF) on outcome in patients with symptomatic atherosclerotic disease has not been thoroughly studied. METHODS: FRENA is an ongoing registry of stable outpatients with coronary (CAD), cerebrovascular (CVD), or peripheral (PAD) artery disease. With the aim to guide therapy, we assessed the incidence of subsequent myocardial infarction (MI), ischemic stroke or major bleeding in patients with AF, according to initial presentation. RESULTS: As of June 2011, 3848 patients were recruited: 1436 had CAD, 1104 CVD, and 1308 had PAD. Of these, 470 (12%) had AF: 151 patients with CAD, 157 with CVD, and 162 with PAD. Over a mean follow-up of 16±13months, 19 patients with AF developed acute MI, 22 ischemic stroke and 7 bled. Among AF patients with CAD, the incidence of subsequent MI (5.00 events per 100 patient-years; 95% CI: 2.54-8.91) was non-significantly higher than that of stroke (1.48; 95% CI: 0.38-4.04) or major bleeding (1.47; 95% CI: 0.37-4.01). Among those with CVD, the incidence of stroke (5.61; 95% CI: 2.95-9.75) exceeded that of MI (no events) or major bleeding (0.51; 95% CI: 1.24-6.36). Among those with PAD, the incidence of MI (4.41; 95% CI: 2.15-8.10) and stroke (3.93; 95% CI: 1.82-7.46) were similar. CONCLUSIONS: CAD patients with AF are at a higher risk of subsequent MI than of stroke. Among those with CVD, the risk of stroke far exceeds that of MI. Those with PAD have a high and similar risk for both events.     

Comparison of the impact of atrial fibrillation on the risk of early death after stroke in women versus men

BACKGROUND: Atrial fibrillation (AF) is considered a predictive factor of poor clinical outcome in patients with an ischemic stroke (IS). This study addressed whether the impact of AF on the in-hospital mortality after first ever IS is different according to the patient's gender. METHODS: We prospectively studied 1678 patients with first ever IS consecutively admitted to two University Hospitals. We recorded demographic data, vascular risk factors, and the stroke severity (NIHSS) at admission analyzing their impact on the in-hospital mortality and on the combined mortality-dependency at discharge using a Cox proportional hazards model. Two variable interactions between those factors independently related to in-hospital mortality and combined mortality-dependency at discharge were tested. RESULTS: Overall in-hospital mortality was 11.3%. Cox proportional hazards model showed that NIHSS at admission (HR: 1.178 [95% CI 1.149-1.207]), age (HR: 1.044 [95% CI 1.026-1.061]), AF (HR: 1.416 [95% CI 1.048-1.913]), male gender (HR: 1.853 [95% CI 1.323-2.192) and ischemic heart disease (HR: 1.527 [95% CI 1.063-2.192]) were independent predictors of in-hospital mortality. A significant interaction between gender and AF was found (p = 0.017). Data were stratified by gender, showing that AF was an independent predictor of poor outcome just for woman (HR: 2.183 [95% CI 1.403-3.396]; p < 0.001). The independent predictors of combined mortality-disability at discharge were NIHSS at admission (HR: 1.052 [95% CI 1.041-1.063]), age (HR: 1.011 [95% CI 1.004-1.018]), AF (HR: 1.197 [95% CI 1.031-1.390]), ischemic heart disease (HR: 1.222 [95% CI 1.004-1.488]), and smoking (HR: 1.262 [95% CI 1.033-1.541]). CONCLUSIONS: The impact of AF is different in the two genders and appears as a specific ischemic stroke predictor of in-hospital mortality just for women.     

Concomitant irritable bowel syndrome is associated with failure of step‐down on‐demand proton pump inhibitor treatment in patients with gastro‐esophageal reflux disease

Background The predictors for treatment failure of on‐demand proton pump inhibitor (PPI) therapy in gastro‐esophageal reflux disease (GERD) patients are unclear. We studied the efficacy and predictors for treatment failure of step‐down on‐demand PPI therapy in patients with non‐erosive reflux disease (NERD) and those with low grade erosive esophagitis. Methods Consecutive symptomatic GERD patients who had positive esophageal pH studies and complete symptom resolution with initial treatment of esomeprazole were given step‐down on‐demand esomeprazole for 26 weeks. Patients with esophagitis of Los Angeles (LA) grade C or above and recent use of PPI were excluded. Treatment failure was defined as an inadequate relief of reflux symptoms using global symptom assessment. Potential predictors of treatment failure were determined using multivariate analysis. Key Results One hundred and sixty three NERD and 102 esophagitis patients were studied. The 26‐week probability of treatment failure was 36.2% (95% CI: 23.9–46.5%) in NERD group and 20.1% (95% CI: 10.9–28.3%) in esophagitis group, respectively (P = 0.021). Irritable bowel syndrome (adjusted HR: 2.1, 95% CI: 1.5–3.8, P = 0.01), in addition to daily reflux symptom (adjusted hazard ratio: 2.7, 95% CI: 1.9–4.2, P = 0.001) and concomitant dyspepsia (adjusted hazard ratio: 1.7, 95% CI: 1.1–2.8, P = 0.04), were independent predictors for treatment failure. Conclusions & Inferences Compared to patients with esophagitis, NERD patients have higher failure rate of on‐demand PPI therapy. Concomitant irritable bowel syndrome, in addition to daily reflux symptom and dyspepsia, is associated with the failure of on‐demand PPI in these patients.     

Rapid Risk Stratification of Acute Ischemic Stroke Patients in the Emergency Department: The Incremental Prognostic Role of Left Atrial Reservoir Strain

ObjectivesTo determine the prognostic value of positive global left atrial strain (LA-GSA+), measured by two-dimensional speckle tracking echocardiography (2D-STE) in a population of acute ischemic stroke (AIS) patients without atrial fibrillation (AF), in the setting of Emergency Department (ED).MethodsAll consecutive AIS patients with sinus rhythm on ECG and without AF history entered this prospective study. All patients underwent complete blood tests and transthoracic echocardiography implemented with 2D-STE analysis of LA strain parameters within 6–12 h after symptoms onset. At 6-months follow-up, we evaluated the composite endpoint of all-cause mortality plus cardiovascular re-hospitalizations.ResultsA total of 102 AIS patients (76.4 ± 10.8 yrs, 47% males) were prospectively included. LA-GSA+ was markedly reduced in AIS patients (20.8 ± 7.7%), without any statistically significant difference between the stroke subtypes. At 6-months follow-up, 7 deaths and 27 re-hospitalizations occurred. On multivariate Cox regression analysis, variables independently associated with outcome were: LA-GSA+ (per unit) (HR 0.29, 95% CI 0.19–0.39) and C-reactive protein (CRP) (per 0.1 mg/dl) (HR 1.45, 95% CI 1.15–1.75) as continuous variables; statin therapy (HR 0.45, 95%CI 0.28–0.62), and type 2 diabetes (HR 1.65, 95% CI 1.15–2.35) as categorical variables. A LA-GSA+ ≤20.0% predicted the occurrence of the above-mentioned outcome at 6-months follow-up with 94% sensitivity and 81% specificity (AUC=0.84). Interestingly, GSA+ showed a strong inverse correlation with CRP levels (r = -0.86).ConclusionsA LA-GSA+ ≤20% reflects a more advanced atrial cardiomyopathy and might provide a rapid and reliable prognostic risk stratification of AIS patients without AF history in the setting of ED.     

Patterns of diffusion‐weighted magnetic resonance imaging associated with etiology improve the accuracy of prognosis after transient ischaemic attack

Objective: Diffusion‐weighted magnetic resonance imaging (DWI) is a sensitive diagnostic tool for detecting acute ischaemic lesions in patients with transient ischaemic attacks (TIAs). The additional predictive value of DWI lesion patterns is not well known. Methods: Two hundred and fifty‐four consecutive patients with TIA underwent DWI within 7 days of symptom onset. The presence and pattern of acute ischaemic lesions were related to clinical features, etiology, and stroke recurrence at seven‐ and 90‐day follow‐up. Results: Diffusion‐weighted images abnormalities were identified in 117 (46.1%) patients. The distribution of DWI lesions was cortical, 31; subcortical, 32; scattered lesions in one arterial territory (SPOT) 42; and in multiple areas, 12. SPOT were significantly associated with motor weakness, large‐artery atherosclerosis (LAA), and the cardioembolic subtype of TIA. Single cortical lesions were also associated with cardioembolism, whereas subcortical acute lesions were associated with recurrent episodes, dysarthria, and motor weakness. During follow‐up, seven patients had a stroke within 7 days (2.8%, 95% CI 2.9–6.4%), and 12 had a stroke within 3 months (4.7%%, 95% CI 2.9–6.4%). In the Cox logistic regression model, the combination of LAA and positive DWI remained as independent predictors of stroke recurrence at 90‐day follow‐up (HR 5.78, 95 CI 1.74–19.21, P = 0.004). Conclusion: According to our results, MRI, including DWI, should be considered a preferred diagnostic test when investigating patients with potential TIAs. The combination of neuroimaging and vascular information could improve prognostic accuracy in patients with TIA.     

A randomised,placebo-controlled 52-week trial of continued quetiapine treatment in recently depressed patients with bipolar I and bipolar II disorder

Objectives. To examine the longer-term efficacy of quetiapine monotherapy in bipolar depression in a preplanned pooling of data from the EMBOLDEN I and II studies. Methods. Patients (N = 584) with bipolar I or II disorder (most recent episode: depressed) who achieved remission after 8 weeks of treatment with quetiapine (300 or 600 mg/day) were randomised to the same quetiapine dose or placebo for 26–52 weeks or until mood event recurrence. Results. The risk for recurrence of a mood event was significantly lower with quetiapine than placebo (HR 0.51 (95% CI: 0.38–0.69); P < 0.001). Quetiapine was associated with a lower risk for recurrence of depressive events (HR 0.43 (95% CI: 0.30–0.62); P < 0.001) but recurrence of manic/hypomanic events was not significantly reduced (HR 0.75 (95% CI: 0.45–1.24; P = 0.263). There was a lower risk of recurrence of mood events in bipolar I (HR 0.58 (95% CI: 0.41–0.82), P = 0.002) and bipolar II patients (HR 0.33 (95% CI: 0.18–0.60), P < 0.001). Discontinuation rates due to adverse events were 4.3, 4.0 and 1.7% for quetiapine 300 mg/day, 600 mg/day and placebo, respectively. Safety data, including changes in lipid and glucose parameters, were consistent with the recognized profile of quetiapine. Conclusions. The efficacy of quetiapine monotherapy in bipolar depression is maintained during continued treatment for 26–52 weeks. Quetiapine was generally well tolerated.     

Causes of death in patients with multiple sclerosis and matched referent subjects: a population‐based cohort study

Background and purpose: Multiple sclerosis (MS) has been associated with increased mortality rates. However, influence of lifestyle parameters remains unknown, and inconsistencies exist regarding findings for causes of death. Methods: We conducted a population‐based cohort study using the General Practice Research Database, Hospital Episode Statistics, and national death certificates (January 2001 through March 2008). To each patient with MS (n = 1270), up to six referent subjects without MS were matched by age, gender, and practice. Cox proportional hazards models were used to estimate mortality rate ratios (HRs). Results: Patients with MS had a 3.5‐fold increased mortality rate for all‐cause mortality, compared with referent subjects (HR 3.51, 95% CI 2.63–4.69). The rate further increased amongst current smokers (HR 6.72, 95% CI 4.16–10.87) (but not in ex‐smokers) and subjects with a body mass index of <20 kg/m² (HR 6.67, 95% CI 3.50–12.73). The HR was highest for infectious/respiratory‐related deaths (HR 7.69, 95% CI 4.92–12.02) and was significantly increased for deaths related to cardiovascular diseases (2.4‐fold) and cancer (1.9‐fold), but not for accidents and suicide related deaths. Conclusion: British patients with MS have a 3.5‐fold increased mortality rate compared with the general population. Smoking and respiratory diseases are major (potentially preventable) factors related to increased mortality rate amongst patients with MS.     

Post-stroke fatigue and return to work: a 2-year follow-up

Andersen G, Christensen D, Kirkevold M, Johnsen SP. Post‐stroke fatigue and return to work: a 2‐year follow‐up.
Acta Neurol Scand: 2012: 125: 248–253.
© 2011 John Wiley & Sons A/S. Background – Post‐stroke fatigue may affect the ability to return to work but quantitative studies are lacking. Method – We included 83 first‐ever stroke patients <60 years and employed either full‐time (n = 77) or part‐time (n = 6) at baseline. The patients were recruited from stroke units at Aarhus University Hospital between 2003 and 2005 and were followed for 2 years. Fatigue was assessed by the Multidimensional Fatigue Inventory. Pathological fatigue was defined as a score ≥12 on the General Fatigue dimension. Return to paid work was defined as working at least 10 h per week. Data were analyzed using multivariable logistic regression. Results – A total of 58% of patients had returned to paid work after 2 years. The adjusted Odds Ratio (OR) for returning to paid work was 0.39 (95% confidence interval (CI) 0.16–1.08) for patients with a General Fatigue score ≥12 at baseline. Persisting pathological fatigue after 2 years of follow‐up was associated with a lower chance of returning to paid work [adjusted OR 0.29 (95% CI 0.11–0.74)]. Higher scores of General Fatigue at follow‐up also correlated negatively with the chance of returning to paid work when analyzing fatigue on a continuous scale (adjusted OR 0.87, 95% CI 0.80–0.94 for each point increase in General Fatigue). Conclusions – Post‐stroke fatigue appears to be an independent determinant of not being able to resume paid work following stroke.     

Low conversion rate of ocular to generalized myasthenia gravis in Singapore

Introduction: Ocular myasthenia gravis (OMG) is a common condition of the neuromuscular junction that may convert to generalized myasthenia gravis (GMG). Our aim in this study was to determine the conversion rate and predictive factors for generalization in OMG, in an Asian population. Methods: The investigation consisted of a retrospective study of OMG patients with a minimum 2 years of follow‐up. Results: Among 191 patients with OMG, 155 had the minimum 2‐year follow‐up. The conversion rate at median follow‐up (40.8 months) was 10.6% (95% confidence interval 7.9%–13.3%), and at the 2‐year follow‐up it was 7.7% (95% confidence interval 5.6%–9.8%). At baseline, the predictive factors for generalization were positive acetylcholine receptor antibodies (hazard ratio 3.71, P = 0.024), positive repetitive nerve stimulation (RNS) studies (hazard ratio 4.42, P = 0.003), and presence of radiologically presumed or pathologically confirmed thymoma (hazard ratio 3.10, P = 0.013). Discussion: The conversion rate of OMG to GMG in Asian patients is low, as predicted by presence of acetylcholine receptor antibodies, presence of thymoma, and positive RNS studies. Muscle Nerve 57 : 756–760, 2018     

Depressive symptoms predispose females to metabolic syndrome: a 7‐year follow‐up study

Objective: To evaluate the risk for developing metabolic syndrome when having depressive symptoms. Method: The prevalence of depressive symptoms and metabolic syndrome at baseline, and after a 7‐year follow‐up as measured with Beck depression inventory (BDI), and using the modified National Cholesterol Education Program – Adult Treatment Panel III criteria for metabolic syndrome (MetS) were studied in a middle‐aged population‐based sample (n = 1294). Results: The logistic regression analysis showed a 2.5‐fold risk (95% CI: 1.2–5.2) for the females with depressive symptoms (BDI ≥10) at baseline to have MetS at the end of the follow‐up. The risk was highest in the subgroup with more melancholic symptoms evaluated with a summary score of the melancholic items in BDI (OR 6.81, 95% CI: 2.09–22.20). In men, there was no risk difference. Conclusion: The higher risks for MetS in females with depressive symptoms at baseline suggest that depression may be an important predisposing factor for the development of MetS.