Multiple sclerosis survival: a population‐based study in Sicily

Background and purpose: There are few population‐based surveys on multiple sclerosis (MS) survival. To investigate MS survival in MS patients recruited during surveys conducted in Sicily. Methods: Multiple sclerosis patients identified during previous surveys were randomly matched to two referent subjects by residence, year of birth, and gender. Living status was obtained by municipality records (end of follow‐up June, 30th 2007) and, for the deceased, date and causes of death were searched. Kaplan‐Meier plots were used to calculate differences in mortality between MS patients and referent subjects. MS risks for mortality with 95% confidence intervals (CI) were also calculated. Results: We included 194 MS patients and 388 matched persons. Thirty MS patients (15.5%) and 28 referents (7.2%) had died until the end of follow‐up. Mean survival from onset of the disease to death was 20.6 years. Mean age at death was 55.5 for MS patients and 64.8 for the referents. Adjusted Hazard Ratios for mortality in MS was 1.81 (95% CI 1.36–2.40). Kaplan‐Meier estimates showed a higher mortality amongst patients compared to referent subjects (P < 0.001). Conclusions: The present study confirms the higher mortality risk in MS patients with no significant gender difference. Causes of death are related to complications of high disability and to increasing age.     

Relationship of initial glucose level and all‐cause death in patients with ischaemic stroke: the roles of diabetes mellitus and glycated hemoglobin level

Background and purpose: Previous studies demonstrated that post‐stroke hyperglycemia was associated with poor outcome in non‐diabetic patients. However, evidence was inconclusive amongst patients with diabetes. The aim of this study was to evaluate the relationship between initial glucose levels and mortality amongst patients with acute ischaemic stroke, and further, to assess whether the association varied by diabetes mellitus and glycated hemoglobin (HbA_1c) levels. Methods: Data were collected from the medical records of 1277 first‐ever stroke patients admitted to the emergency room between January 1, 2008 and June 30, 2009. Cox regression analysis was performed to assess the relationship between initial glucose level and mortality. Results: Compared with the lowest quartile of initial glucose level, a significant association with all‐cause death [hazard ratio (HR), 2.18; 95% CI, 1.36–3.48] and cardiovascular death (HR, 1.91; 95% CI, 1.01–3.61) was seen in the highest quartile. In non‐diabetic subgroup, those patients within the highest quartile of initial glucose level had a 3.29‐fold relative risks (RR) [95% confidence interval (CI), 1.62–6.68] for all‐cause and a 2.54‐fold RR (95% CI, 1.43–8.77) for cardiovascular death compared with those within the lowest quartile. However, the association between initial glucose levels and the risk of death was not significant amongst those with diabetes (P for interaction = 0.01). In addition, the risk amongst patients with diabetes varied by the HbA_1c levels. Conclusions: A significant association was confirmed between initial glucose level and mortality in non‐diabetic ischaemic stroke patients. The possible relationship between initial glucose level, HbA_1c level, and mortality amongst ischaemic stroke patients with diabetes warrants further research.     

High mortality from Guillain‐Barré syndrome in Bangladesh

Although Guillain‐Barré syndrome (GBS) has higher incidence and poor outcome in Bangladesh, mortality from GBS in Bangladesh has never been explored before. We sought to explore the frequency, timing, and risk factors for deaths from GBS in Bangladesh. We conducted a prospective study on 407 GBS patients who were admitted to Dhaka Medical College Hospital, Dhaka, Bangladesh from 2010 to 2013. We compared deceased and alive patients to identify risk factors. Cox regression model was used to adjust for confounders. Of the 407 GBS patients, 50 (12%) died, with the median time interval between the onset of weakness and death of 18 days. Among the fatal cases, 24 (48%) were ≥40 years, 36 (72%) had a Medical Research Council sum score ≤20 at entry, 33 (66%) had a progressive phase <8 days, and 27 (54%) required ventilation support. Ten patients (20%) died due to unavailability of ventilator. The strongest risk factor for deaths was lack of ventilator support when it was required (HR: 11.9; 95% confidence interval [CI]: 4.6–30.7). Other risk factors for death included age ≥40 years (HR: 5.9; 95% CI: 2.1–16.7), mechanical ventilation (HR: 2.3; 95% CI: 1.02–5.2), longer progressive phase (>8 days) (HR: 2.06; 95% CI: 1.1–3.8), autonomic dysfunction (HR: 1.9; 95% CI: 1.05–3.6), and bulbar nerve involvement (HR: 5.4; 95% CI: 1.5–19.2). In Bangladesh, GBS is associated with higher mortality rates, which is related to lack of ventilator support, disease severity, longer progressive phase of the disease, autonomic dysfunction, and involvement of the bulbar nerves.     

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.     

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.     

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     

Parkinson's disease and risk of mortality: meta‐analysis and systematic review

To evaluate the existing prospective observational studies on the morality risk among Parkinson's disease (PD) patients and determine the overall risk ratio (RR) of mortality by conducting a meta‐analysis and systematic review. Original articles published in English were searched in PubMed and Embase databases prior to March 2013. Only prospective observational studies providing adjusted risk estimates related to PD and future mortality were considered eligible. Pooled adjusted RR and 95% confidence interval (CI) were computed either by fixed‐effects models or by random‐effects models. Eight studies with 72,833 participants were identified and analysed. In the pooled analyses, patients with PD had a greater risk of all‐cause mortality (RR = 2.22; 95% CI: 1.78–2.77). Subgroup analyses based on the design, gender, follow‐up duration and sample size showed that a consistent positive association between PD and the mortality risk in each subgroup. However, no statistical significance was found for the baseline age <65 years (RR = 1.42; 95% CI: 0.72–2.77). PD patients with dementia had particularly high mortality risks (RR = 3.78; 95% CI: 2.06–6.92). This meta‐analysis indicated that among patients with PD, the all‐cause mortality increased by 2.22‐fold compared with the general population. PD patients with dementia particularly had higher risks of mortality.     

Mortality risk in adults with newly diagnosed and chronic epilepsy: a population‐based study

Background: We analyzed mortality in adult patients with newly diagnosed and chronic epilepsy over a 13‐year period. Methods: Eighty‐one patients aged ≥20 years with newly diagnosed epilepsy and 309 adult patients with chronic epilepsy were originally identified from population‐based incidence and prevalence studies conducted in Tartu between 1994 and 1996. Patients with epilepsy were followed until the date of death or until the end of 2007. The standardized mortality ratio (SMR) was analyzed for both cohorts. The influences of age at diagnosis, sex, epilepsy syndrome, seizure type, risk factors and treatment compliance on the SMR were also investigated. Results: The SMR was significantly increased in both cohorts, but was higher in patients with chronic epilepsy (SMR 3.1; 95% confidence interval [CI] 2.5–3.8) relative to patients with newly diagnosed epilepsy (SMR 2.6; 95% CI 1.8–3.5). In the newly diagnosed epilepsy cohort, the increased mortality risk was more pronounced in patients with complex partial seizures (SMR 5.6; 95% CI 2.4–11.0). In the chronic epilepsy cohort, the mortality risk was higher in patients with secondary generalized tonic‐clonic seizures (SMR 3.4; 95% CI 2.5–4.5). Non‐compliant patients had twice the mortality risk (SMR 4.2; CI 95% 2.7–6.2) compared to those who were on anticonvulsant treatment. Conclusions: Mortality rates are higher in people with newly diagnosed and chronic epilepsy. Mortality risks should be discussed with patients with epilepsy, especially if anticonvulsant treatment is refused despite recurrent seizures.     

Oligoclonal bands predict multiple sclerosis in children with optic neuritis

We retrospectively evaluated predictors of conversion to multiple sclerosis (MS) in 357 children with isolated optic neuritis (ON) as a first demyelinating event who had a median follow‐up of 4.0 years. Multiple Cox proportional‐hazards regressions revealed abnormal cranial magnet resonance imaging (cMRI; hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.39–10.39, p < 0.001), presence of cerebrospinal fluid immunoglobulin G oligoclonal bands (OCB; HR = 3.69, 95% CI = 2.32–5.86, p < 0.001), and age (HR = 1.08 per year of age, 95% CI = 1.02–1.13, p = 0.003) as independent predictors of conversion, whereas sex and laterality (unilateral vs bilateral) had no influence. Combined cMRI and OCB positivity indicated a 26.84‐fold higher HR for developing MS compared to double negativity (95% CI = 12.26−58.74, p < 0.001). Accordingly, cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON. Ann Neurol 2015;77:1076–1082     

Mortality of patients with multiple sclerosis: a cohort study in UK primary care

We aimed to estimate rates, causes and risk factors of all-cause mortality in a large population-based cohort of multiple sclerosis (MS) patients compared with patients without MS. Using data from the UK General Practice Research Database, we identified MS cases diagnosed during 2001–2006 and validated using patients’ original records where possible. We also included MS cases during 1993–2000 identified and validated in an earlier study. Cases were matched to up to ten referents without MS by age, sex, index date (date of first MS diagnosis for cases and equivalent reference date for controls), general practice and length of medical history before first MS diagnosis. Patients were followed up to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox-proportional regression. MS patients (N = 1,822) had a significantly increased risk of all-cause mortality compared with referents (N = 18,211); adjusted HR 1.7 (95 % CI 1.4–2.1). Compared with referents, female MS patients had a higher but not significantly different HR for death than males; adjusted HR 1.86 (95 % CI 1.46–2.38) vs. HR 1.31 (95 % CI 0.93–1.84), respectively. The most commonly recorded cause of death in MS patients was ‘MS’ (41 %), with a higher proportion recorded among younger patients. A significantly higher proportion of referents than MS patients had cancer recorded as cause of death (40 vs. 19 %). Patients with MS have a significant 1.7-fold increased risk of all-cause mortality compared with the general population. MS is the most commonly recorded cause of death among MS patients.     

Depressive symptoms and mortality-findings from Helsinki birth cohort study

Background

Individuals with depression and depressive symptoms have a higher mortality rate than non-depressed individuals. The increased comorbidity and mortality associated with depression has remained largely unexplained. The underlying pathophysiological differences between depressive subtypes, melancholic and non-melancholic, may provide some explanation to this phenomenon.

Methods

One thousand nine hundred and ninety five participants (mean age 61 years) from the Helsinki Birth Cohort Study were recruited for this prospective study and followed up for a mean of 14.1 years. Information regarding medical history, lifestyle, and biochemical parameters were obtained. Depressive symptoms were assessed using the Beck Depression Inventory. Standardized mortality ratios were calculated.

Results

Participants were followed up for a total of 28,044 person-years. The melancholic depressive group had an increased adjusted risk of mortality [HR 1.49 (95% CI: 1.02–2.20)] when compared to the non-depressive group. Comparing mortality to the whole population of Finland using standardized mortality ratios (SMR) both the non-melancholic [1.11 (95% CI: 0.85–1.44)] and melancholic depressive [1.26 (95% CI: 0.87–1.81)] groups had higher mortality than the non-depressive group [0.82 (95% CI: 0.73–0.93)].

Conclusions

Melancholic depressive symptoms are most strongly related to a higher mortality risk.     

Mortality risk in a nationwide cohort of individuals with tic disorders and with tourette syndrome

Background : Few studies have investigated mortality risk in individuals with tic disorders. Methods : We thus measured the risk of premature death in individuals with tic disorders and with Tourette syndrome in a prospective cohort study with 80 million person‐years of follow‐up. We estimated mortality rate ratios and adjusted for calendar year, age, sex, urbanicity, maternal and paternal age, and psychiatric disorders to compare individuals with and without tic disorders. Results : The risk of premature death was higher among individuals with tic disorders (mortality rate ratio, 2.02; 95% CI, 1.49‐2.66) and with Tourette syndrome (mortality rate ratio, 1.63; 95% CI, 1.11‐2.28) compared with controls. After the exclusion of individuals with comorbid attention‐deficit/hyperactivity disorder, obsessive‐compulsive disorder, and substance abuse, tic disorder remained associated with increased mortality risk (mortality rate ratio, 2.30; 95% CI, 1.57‐3.23), as did also Tourette Syndrome (mortality rate ratio, 1.81; 95% CI, 1.11–2.75). Conclusions : These results are of clinical significance for clinicians and advocacy organizations. Several factors may contribute to this increased risk of premature death, and more research mapping out these factors is needed. © 2017 International Parkinson and Movement Disorder Society     

Effect of statin treatment on three-month outcomes in patients with stroke-associated infection: a prospective cohort study

Background and purpose: Infection is a major medical problem in patients with acute stroke. Recent evidences suggest that statins reduce infection‐associated complications. The purpose of this study was to examine the influence of statin treatment on mortality and functional outcomes in patients with stroke‐associated infection. Methods: In this prospective observational cohort study, 514 patients with acute ischaemic stroke or transient ischaemic attack (mean age, 74 ± 11 years; men, 48%) with infection occurring in the first 7 days after admission were included. We examined the effect of in‐hospital statin treatment on mortality and favorable functional outcome (modified Rankin Scale score ≤2) at 3 months follow‐up. Results: Infection occurred at 0.93 ± 1.49 days after admission. All patients had not received statin treatment prior to admission, and 121 patients (24%) received statin at 1.71 ± 1.28 days after admission. Follow‐up at 3 months was completed for 511 patients (99%). National Institutes of Health Stroke Scale score and Charlson index were the most important independent predictors of mortality and functional outcome. Univariate [hazard ratio (HR), 0.82; 95% confidence intervals (CI), 0.47–1.42] and multivariate (HR, 1.68; 95% CI, 0.79–3.56) Cox regression analysis showed that statin did not significantly decrease the morality. In propensity analysis, statin treatment still had no significant association with mortality (HR, 1.54; 95% CI, 0.68–3.47) in the multivariate analyses after adjusting for age, sex, and propensity score. Conclusions: Statin use was not associated with a better functional outcome or survival in patients with stroke‐associated infection.     

Falling status epilepticus mortality rates in England and Wales: 2001–2013?

Status epilepticus (SE) is associated with significant mortality and accounts for ~10% of epilepsy‐related deaths. Epilepsy and SE mortality data from 2001 to 2013, in addition to annual age group populations for England and Wales, were obtained from the Office of National Statistics website ( www.ons.gov.uk ). Age‐adjusted mortality rates for epilepsy and SE with 95% confidence intervals (CIs) were calculated using the European Standard Population. Trends in mortality rates for both epilepsy and SE were investigated using the Spearman coefficient. The crude mean epilepsy mortality rate per 100,000 person‐years between 2001 and 2013 was 1.87 (95% CI 1.83–1.91), with a corresponding SE mortality rate of 0.14 (95% CI 0.13–0.15). The mean age‐adjusted epilepsy mortality rate per 100,000 person years was 3.24 (95% CI 3.12–3.35), with a corresponding SE mortality rate of 0.24 (95% CI 0.21–0.27). All epilepsy deaths significantly decreased from 2001 to 2013 (Spearman's ρ ?0.733, p = 0.004); this decrease was predominantly due to a decrease in SE deaths (Spearman's ρ ?0.917, p < 0.001). In summary, our finding supports the hypothesis that the policy of early and aggressive treatment of SE may be improving the prognosis of this condition in England and Wales.     

Mortality in Parkinson's disease and its association with dementia and depression

OBJECTIVE: To compare the mortality rate in Parkinson's disease (PD) with a control group without PD, and to assess the relationship between mortality and features of PD. MATERIAL AND METHODS: Ninety PD patients and 50 controls, mortality ascertained at 11 years follow-up. RESULTS: The hazard ratio (HR) for mortality in PD patients compared with controls was 1.64 (95% CI: 1.21-2.23). Multivariate analysis showed age, dementia and depression were independent predictors of mortality but age at onset of PD and severity of neurological symptoms were not. The HR for age was 1.09 (95% CI: 1.05-1.13), for dementia 1.94 (95% CI: 1.26-2.99), and for depression 2.66 (95% CI: 1.59-4.44). CONCLUSION: Mortality in PD is increased compared with controls. Psychological variables are important predictors of mortality in PD.     

Cigarette Smoking and Mortality Risk in People With Schizophrenia

This study examined effects of cigarette smoking on mortality risk in 1213 persons aged 19–69 years with schizophrenia-related psychotic disorders admitted to State of Maryland Hospitals between 1994 and 2000. Inpatient medical records from 7 hospitals were reviewed to obtain demographic information, diagnosis, medication use, as well as smoking and other substance use. Social Security Death Index data were used to identify deaths in the study group between 1994 and 2004. Death records were reviewed to obtain manner of death and underlying disorders. Of the 1213, 55% were smokers and 71% abused substances. There was an age × smoking interaction (χ² = 14.6, df = 1, P = .0001) for mortality, with estimated hazard ratios (HRs) for smokers vs nonsmokers of 2.1 among 35- to 54-year olds and HR of 0.7 among those aged 55–69 years. Five- and 10-year mortality rates for smokers aged 35–54 years were 7.0% and 14.2%, compared with 3.3% and 10.0% for nonsmokers, respectively (χ² = 5.53, df = 1, P = .019). Cardiac causes were identified in 43% of deaths in smokers but only 19% of deaths in nonsmokers (P < .006). For those aged 35–54 years, the odds of cardiac related death was increased by 12 fold in smokers relative to nonsmokers (HR = 12.4, χ² = 12.0, df = 1, P = .0005). Among people aged 35–54 years, those smoking greater than one pack daily have a significantly increased total mortality risk (HR = 2.7) vs nonsmokers. Cigarette smoking, particularly in people aged 35–54 years, contributes to an increased risk of death. Greater smoking severity significantly increases this risk. Smoking cessation in people with schizophrenia deserves significant attention.     

Depressive symptoms as an independent risk factor for mortality in elderly persons: Results of a national longitudinal study

Objective: Depressive symptoms have been associated with increased mortality risk in previous cohort studies, but there is a paucity of research on Asian elderly in recent years. The authors investigated the depression–mortality link using data from a representative national cohort.

Methods: Data came from the Survey of Health and Living Status of the Elderly in Taiwan. A cohort of 2416 men and women in Taiwan aged 65 or older were followed up for eight years from 1999 to 2007. Depressive symptoms were assessed by the 10-item Center for Epidemiologic Studies Depression Scale. The mortality risk of depression was computed after adjustment for a variety of covariates. Data on the presence or absence of chronic diseases were further analyzed.

Results: Overall, depressive symptoms were associated with all-cause mortality (hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.03–1.42) after eight years follow-up, but this mortality risk was detected in men only (HR, 1.27; 95% CI, 1.03–1.56), not in women (HR, 1.1; 95% CI, 0.86–1.4). Further analyses showed that in the group without chronic diseases (without diabetes mellitus, stroke, lung disease, cancer, or cognitive impairment), depressive symptoms were associated with mortality (HR, 1.40; 95% CI, 1.12–1.76) after eight years follow-up; however, there was no association between depressive symptoms and mortality in participants with chronic diseases (HR, 1.02; 95% CI, 0.82–1.26).

Conclusion: Depressive symptoms are an independent risk factor for mortality in the elderly. Elderly depressive men and elderly without chronic diseases seemed to have a greater mortality risk.     

Mortality in epilepsy in the first 11 to 14 years after diagnosis: multivariate analysis of a long-term, prospective, population-based cohort

The United Kingdom National General Practice Study of Epilepsy is a prospective, population-based study of newly diagnosed epilepsy. A cohort of 792 patients has now been followed for up to 14 years (median follow-up [25th, 75th percentiles] 11.8 years, range 10.6-11.7 years), a total of 11,400 person-years. These data are sufficient for a detailed analysis of mortality in this early phase of epilepsy. Over 70% of patients in this cohort have developed lasting remission from seizures, although the mortality rate in the long term was still twice that of the general population. The standardized mortality ratio (SMR), the number of observed deaths per number of expected deaths, was 2.1 (95% confidence interval [CI] = 1.8, 2.4). Patients with acute symptomatic epilepsy (SMR 3.0; 95% CI = 2.0, 4.3), remote symptomatic epilepsy (SMR 3.7; 95% CI = 2.9, 4.6), and epilepsy due to congenital neurological deficits (SMR 25; 95% CI = 5.1, 73.1) had significantly increased long-term mortality rates, whereas patients with idiopathic epilepsy did not (SMR 1.3; 95% CI = 0.9, 1.9). This increase in mortality rate was noted particularly in the first few years after diagnosis. Multivariate Cox regression and time-dependent co-variate analyses were utilized for the first time in a prospective study of mortality in epilepsy. The former showed that patients with generalized tonic-clonic seizures had an increased risk of mortality. The hazard ratio (HR), or risk of mortality in a particular group with a particular risk factor compared to another group without that particular risk factor, was 6.2 (95% CI = 1.4, 27.7; p = 0.049). Cerebrovascular disease (HR 2.4; 95% CI = 1.7, 3.4; p < 0.0001), central nervous system tumor (HR 12.0; 95% CI = 7.9, 18.2; p < 0.0001), alcohol (HR 2.9; 95% CI = 1.5, 5.7; p = 0.004), and congenital neurological deficits (HR 10.9; 95% CI = 3.2, 36.1; p = 0.003) as causes for epilepsy and older age at index seizure (HR 1.9; 95% CI = 1.7,2.0; p < 0.0001) were also associated with significantly increased mortality rates. These hazard ratios suggest that epilepsy due to congenital neurological deficits may carry almost the same risk of mortality as epilepsy due to central nervous system tumors and that epileptic seizures subsequent to alcohol abuse may carry almost the same risk of mortality as epilepsy due to cerebrovascular disease. The occurrence of one or more seizures before the index seizure (the seizure that led to the diagnosis of epilepsy and enrolment in the study) was associated with a significantly reduced mortality rate (HR 0.57; 95% CI = 0.42, 0.76; p = 0.00001). Time-dependent co-variate analysis was used to examine the influence of ongoing factors, such as seizure recurrence, remission, and antiepileptic drug use, on mortality rates in the cohort. Seizure recurrence (HR 1.30; 95% CI = 0.84, 2.01) and antiepileptic drug treatment (HR 0.97; 95% CI = 0.67, 1.38) did not influence mortality rate. There were only 5 epilepsy-related deaths (1 each of sudden unexpected death in epilepsy, status epilepticus, burns, drowning, and cervical fracture), suggesting that death directly due to epileptic seizures is uncommon in a population-based cohort with epilepsy.     

Mortality in a population-based cohort of patients treated with antiparkinsonian drugs

Objectives - A number of studies have been focused on the mortality of parkinsonian patients, as compared with the rest of the population. In these studies, a mortality greater than expected on the basis of mortality of the general population has been shown. Nevertheless, just a few of these studies have investigated in detail the specific causes of death, probably as a consequence of both small cohort sizes and a short time period of observation. The aim of this study was to estimate cause-specific mortality in a cohort of patients treated with antiparkinsonian drugs. Methods - The study was performed on a wide population-based cohort of patients identified and followed-up through the computerized health databases of the Italian province of Rome (about 3,800,000 inhabitants). The follow-up lasted from January 1987 to December 1994. Standardized Mortality Ratios (SMR) were calculated for each specific cause of death, using the Rome province population as reference. Results - A cohort of 10,322 subjects, receiving antiparkinsonian drugs, were identified. There were 4328 deaths on an average follow-up of 5.7 years. This figure was 17% higher than was expected. A gradual decrease in SMR was observed in the oldest age groups. Statistically significant (95%) excesses of death were related to the nervous system (SMR=1037; 95% CI 964–1110), mental disorders (SMR=182; 95% CI 129–246), and endocrine and metabolic diseases (SMR=117; 95% CI 102–133). Lower than expected mortality was found to be caused by malignant neoplasms (SMR=56; 95% CI 51–61). Conclusions - Apart from deaths specifically related to Parkinson's disease, the main differences between our cohort of patients and the general population were related to mortality due to malignant neoplasms and mental disorders. The gradual decrease in SMR for the oldest age groups, seems to indicate a greater reduction of life expectancy for patients with early onset of symptoms. This age-related trend could explain the relatively small excess of mortality, as in our cohort the median age of patients at entry was 74 years.     

Juvenile mortality,mental disturbances and criminality: a prospective study of the Northern Finland 1966 birth cohort

Mortality, criminality and mental illness among young adults were studied in an unselected birth cohort of 12 058 children born live in Northern Finland during 1966. The cohort members were followed up to the age of 27 years. The total number of all deaths was 117, and 79.5% of these deaths were from unnatural causes. The mortality of males was more than threefold higher than that of females. There was a significantly higher mortality risk in men with schizophrenia (OR, 9.31; 95% CI, 3.14–25.53), other psychoses (OR, 10.28; 95% CI, 2.40–37.02), personality disorders (OR, 4.28; 95% CI, 1.04–14.67) and combined personality disorders and criminality (OR, 3.27,95% CI, 0.99–9.59). In the group of major mental disorders, 75% of deaths were suicides.