Reducing all-cause mortality among patients with psychiatric disorders: a population-based study

Background:

Among patients with psychiatric disorders, there are 10 times as many preventable deaths from physical disorders as there are from suicide. We investigated whether compulsory community treatment, such as community treatment orders, could reduce all-cause mortality among patients with psychiatric disorders.

Methods:

We conducted a population-based survival analysis of an inception cohort using record linking. The study period extended from November 1997 to December 2008. The cohort included patients from all community-based and inpatient psychiatric services in Western Australia (state population 1.8 million). We used a 2-stage design of matching and Cox regression to adjust for demographic characteristics, previous use of health services, diagnosis and length of psychiatric history. We collected data on successive cohorts for each year for which community treatment orders were used to measure changes in numbers of patients, their characteristics and outcomes. Our primary outcome was 2-year all-cause mortality. Our secondary outcomes were 1-and 3-year all-cause mortality.

Results:

The study population included 2958 patients with community treatment orders (cases) and 2958 matched controls (i.e., patients with psychiatric disorders who had not received a community treatment order). The average age for cases and controls was 36.7 years, and 63.7% (3771) of participants were men. Schizophrenia and other nonaffective psychoses were the most common diagnoses (73.4%) among participants. A total of 492 patients (8.3%) died during the study. Cox regression showed that, compared with controls, patients with community treatment orders had significantly lower all-cause mortality at 1, 2 and 3 years, with an adjusted hazard ratio of 0.62 (95% confidence interval 0.45–0.86) at 2 years. The greatest effect was on death from physical illnesses such as cancer, cardiovascular disease or diseases of the central nervous system. This association disappeared when we adjusted for increased outpatient and community contacts with psychiatric services.

Interpretation:

Community treatment orders might reduce mortality among patients with psychiatric disorders. This may be partly explained by increased contact with health services in the community. However, the effects of uncontrolled confounders cannot be excluded.Mortality among patients with psychiatric disorders is higher than in the general population.¹ Chronic physical disorders such as cardiovascular disease and cancer are the main causes of death in this population, with risks 10 times that of suicide; however, such causes receive far less attention than suicides.^1,2 Patients with schizophrenia die 15–20 years earlier than people in the general population, a difference that has increased over time.^1,3 Reasons for this difference include socioeconomic disadvantage, adverse effects of medication and reduced access to health care.^4,5There are limited data on possible interventions aimed at preventing such deaths, most of which stress regular monitoring of physical status, peer support and collaboration with primary care.^6,7 One study from Victoria, Australia, found that patients on conditional release from hospital had lower mortality than expected when use of community care, age, sex, inpatient experience and diagnosis were taken into account.⁸ However, 10% of these patients had dementia or other diseases of the nervous system, and patients with these diagnoses made up 29% of the deaths in the study. Dementia is not a typical indication for compulsory community treatment. In addition, Victoria has one of the highest levels of use of community treatment orders, about 60 per 100 000 population; thus, those results may not be generalizable to other locales.⁸ Although the authors controlled for time at risk, death could occur from 1 day to 11 years after the index date;⁹ most evaluations of community treatment orders are limited to 1 or 2 years after the order is issued.^9,10 Finally, the results were not adjusted for patients’ marital status, education, country of birth, indigenous status or use of health services before the introduction of community treatment orders. Adjusting for these variables could reduce the bias inherent in drawing cases and controls from the same jurisdiction given the difficulties in controlling for all possible reasons for issuing these orders once they have been introduced.We sought to assess the impact of community treatment orders on 1-, 2-, and 3-year survival in Western Australia. Community treatment orders provide a legal framework within which patients with a serious mental disorder are required to accept psychiatric treatment while living outside hospital. These orders are used across both Canada and Australia, are of similar duration in both countries, and are clinician-initiated rather than court-ordered (in contrast to the United States).^10,11 Unlike in Canada, patients in Australia can be given community treatment orders without having been previously admitted to hospital. In practice, patients in both countries spend similar amounts of time in hospital before being given a community treatment order.¹²We focused on deaths from physical illness, rather than suicides, as these are the most common causes of preventable death among people with severe mental illness.^1,2 We thought that patients with community treatment orders would have lower mortality because of improved engagement with health services, thus allowing greater monitoring and management of physical health. Greater engagement would be shown via increased outpatient contacts following the receipt of a community treatment order, which would influence any association between compulsory community treatment and mortality.     

Long-term survival of patients with prostate cancer in Martinique: Results of a population-based study

BackgroundMartinique has one of the highest incidences of prostate cancer (PCa) worldwide. We analysed overall survival (OS) among patients with PCa in Martinique, using data from a population-based cancer registry between 2005 and 2014.MethodsThe log-rank test was used to assess the statistical differences between survival curves according to age at diagnosis, risk of disease progression including Gleason score, stage at diagnosis and Prostate Specific Antigen (PSA). A multivariable Cox model was constructed to identify independent prognostic factors for OS.ResultsA total of 5045 patients were included with a mean age at diagnosis of 68.1±9.0 years [36.0 – 98.0 years]. Clinical stage was analysed in 4999 (99.1% of overall), 19.5% were at low risk, 34.7% intermediate and 36.9% at high risk. In our study, 8.9% of patients with available stage at diagnosis, were regional/metastatic cancers. Median PSA level at diagnosis was 10.4 ng/mL. High-risk PCa was more frequent in patients aged 65-74 and ≥75 years as compared to those aged <65 years (36.6% and 48.8% versus 28.7% respectively; p<0.0001). One-year OS was 96.3%, 5-year OS was 83.4 and 10-year OS was 65.0%. Median survival was not reached in the whole cohort. High-risk PCa (HR=2.32; p<0.0001), regional/metastatic stage (HR= 9.51; p<0.0001) and older age (65-74 and ≥75 years - respectively HR=1.70; and HR=3.38), were independent prognostic factors for OS (p<0.0001).ConclusionThis study provides long term data that may be useful in making cancer management decisions for patients with PCa in Martinique.     

Long-term mortality in patients with tuberculous meningitis: a Danish nationwide cohort study

Background

With high short-term mortality and substantial excess morbidity among survivors, tuberculous meningitis (TBM) is the most severe manifestation of extra-pulmonary tuberculosis (TB). The objective of this study was to assess the long-term mortality and causes of death in a TBM patient population compared to the background population.

Methods

A nationwide cohort study was conducted enrolling patients notified with TBM in Denmark from 1972–2008 and alive one year after TBM diagnosis. Data was extracted from national registries. From the background population we identified a control cohort of individuals matched on gender and date of birth. Kaplan-Meier survival curves and Cox regression analysis were used to estimate mortality rate ratios (MRR) and analyse causes of death.

Findings

A total of 55 TBM patients and 550 individuals from the background population were included in the study. Eighteen patients (32.7%) and 107 population controls (19.5%) died during the observation period. The overall MRR was 1.79 (95%CI: 1.09–2.95) for TBM patients compared to the population control cohort. TBM patients in the age group 31–60 years at time of diagnosis had the highest relative risk of death (MRR 2.68; 95%CI 1.34–5.34). The TBM patients had a higher risk of death due to infectious disease, but not from other causes of death.

Conclusion

Adult TBM patients have an almost two-fold increased long-term mortality and the excess mortality stems from infectious disease related causes of death.     

Genotype-phenotype correlations for nervous system tumors in neurofibromatosis 2: a population-based study

Neurofibromatosis 2 (NF2) is an autosomal dominant disease that is characterized by tumors on the vestibular branch of the VIII cranial nerve, but other types of nervous system tumors usually occur as well. Genotype-phenotype correlations are well documented for overall NF2 disease severity but have not been definitively evaluated for specific types of non-VIII nerve tumors. We evaluated genotype-phenotype correlations for various types of non-VIII nerve tumors in 406 patients from the population-based United Kingdom NF2 registry, using regression models with the additional covariates of current age and type of treatment center (specialty or nonspecialty). The models also permitted consideration of intrafamilial correlation. We found statistically significant genotype-phenotype correlations for intracranial meningiomas, spinal tumors, and peripheral nerve tumors. People with constitutional NF2 missense mutations, splice-site mutations, large deletions, or somatic mosaicism had significantly fewer tumors than did people with constitutional nonsense or frameshift NF2 mutations. In addition, there were significant intrafamilial correlations for intracranial meningiomas and spinal tumors, after adjustment for the type of constitutional NF2 mutation. The type of constitutional NF2 mutation is an important determinant of the number of NF2-associated intracranial meningiomas, spinal tumors, and peripheral nerve tumors.     

Comparative study on different therapies on patients with primary central nervous system lymphoma

Objective

To compare and analyze three therapies on patients with primary central nervous system lymphoma (PCNSL), aiming to provide evidences for future treatment and prognosis.

Living alone and alcohol-related mortality: a population-based cohort study from Finland

Background

Social isolation and living alone are increasingly common in industrialised countries. However, few studies have investigated the potential public health implications of this trend. We estimated the relative risk of death from alcohol-related causes among individuals living alone and determined whether this risk changed after a large reduction in alcohol prices.

Methods and Findings

We conducted a population-based natural experimental study of a change in the price of alcohol that occurred because of new laws enacted in Finland in January and March of 2004, utilising national registers. The data are based on an 11% sample of the Finnish population aged 15–79 y supplemented with an oversample of deaths. The oversample covered 80% of all deaths during the periods January 1, 2000–December 31, 2003 (the four years immediately before the price reduction of alcohol), and January 1, 2004–December 31, 2007 (the four years immediately after the price reduction). Alcohol-related mortality was defined using both underlying and contributory causes of death. During the 8-y follow-up about 18,200 persons died due to alcohol-related causes. Among married or cohabiting people the increase in alcohol-related mortality was small or non-existing between the periods 2000–2003 and 2004–2007, whereas for those living alone, this increase was substantial, especially in men and women aged 50–69 y. For liver disease in men, the most common fatal alcohol-related disease, the age-adjusted risk ratio associated with living alone was 3.7 (95% confidence interval 3.3, 4.1) before and 4.9 (95% CI 4.4, 5.4) after the price reduction (p<0.001 for difference in risk ratios). In women, the corresponding risk ratios were 1.7 (95% CI 1.4, 2.1) and 2.4 (95% CI 2.0, 2.9), respectively (p ≤ 0.01). Living alone was also associated with other mortality from alcohol-related diseases (range of risk ratios 2.3 to 8.0) as well as deaths from accidents and violence with alcohol as a contributing cause (risk ratios between 2.1 and 4.7), both before and after the price reduction.

Conclusions

Living alone is associated with a substantially increased risk of alcohol-related mortality, irrespective of gender, socioeconomic status, or the specific cause of death. The greater availability of alcohol in Finland after legislation-instituted price reductions in the first three months of 2004 increased in particular the relative excess in fatal liver disease among individuals living alone. Please see later in the article for the Editors'' Summary     

Sex differences in mortality: results from a population-based study of 12 longitudinal cohorts

BACKGROUND:Women generally have longer life expectancy than men but have higher levels of disability and morbidity. Few studies have identified factors that explain higher mortality in men. The aim of this study was to identify potential factors contributing to sex differences in mortality at older age and to investigate variation across countries.METHODS:This study included participants age ≥ 50 yr from 28 countries in 12 cohort studies of the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. Using a 2-step individual participant data meta-analysis framework, we applied Cox proportional hazards modelling to investigate the association between sex and mortality across different countries. We included socioeconomic (education, wealth), lifestyle (smoking, alcohol consumption), social (marital status, living alone) and health factors (cardiovascular disease, diabetes, mental disorders) as covariates or interaction terms with sex to test whether these factors contributed to the mortality gap between men and women.RESULTS:The study included 179 044 individuals. Men had 60% higher mortality risk than women after adjustment for age (pooled hazard ratio [HR] 1.6; 95% confidence interval 1.5–1.7), yet the effect sizes varied across countries (I² = 71.5%, HR range 1.1–2.4). Only smoking and cardiovascular diseases substantially attenuated the effect size (by about 22%).INTERPRETATION:Lifestyle and health factors may partially account for excess mortality in men compared with women, but residual variation remains unaccounted for. Variation in the effect sizes across countries may indicate contextual factors contributing to gender inequality in specific settings.

Life expectancy has increased over the last 6 decades in many societies around the world.¹ Women generally have longer life expectancy than men, yet have higher levels of disability and morbidity.^2,3 Male:female mortality ratios increased from the beginning of the 19th century and slightly decreased over the last 3 decades.^4,5 It has been suggested that the biological differences between the sexes, including genetics and hormones, provide stronger resilience to disadvantageous situations for women than men.⁶ However, biological sex is related to gender, a construct that also incorporates cultural and social differences between men and women. Although some studies suggest that the recent reduction in the male:female mortality ratio is likely a result of improvements in men’s health, lifestyle or occupational environments, others attribute it to women’s changing societal roles and increasing mortality from diseases such as lung cancer, which have traditionally affected mostly men.^3,7–9 Many studies have examined the potential impact of social, behavioural and biological factors on sex differences in mortality,^10,11 but few have been able to investigate potential variation across countries. Different cultural traditions, historical contexts, and economic and societal development may influence gender experiences in different countries, and thus variably affect the health status of men and women.We aimed to identify factors that may explain the difference in mortality risk between men and women at older age and to investigate potential variation across countries, using the harmonized data set of 12 cohort studies from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium.¹²     

Bacteriology of abscesses of the central nervous system: a multicentre prospective study.

Pus from 46 patients with abscesses of the central nervous system (CNS) was examined for bacteria; bacteria were found in all patients. Streptococci were isolated from 36 patients and most isolates were Streptococcus milleri, Lancefield Group F, Ottens and Winkler type O III. Staphylococci were isolated from nine patients, organisms of the bacteroides group from 11, Proteus spp from seven, Klebsiella aerogenes from one, and Haemophilus aphrophilus from one. Pure cultures predominated over mixed cultures. Streptococci were isolated from abscesses of all types, and at all sites, but members of the Enterobacteriaceae and of the bacteroides group were isolated, in mixed cultures, principally from abscesses of the temporal lobe secondary to infection of the middle ear. Staphylococci predominated in abscesses that followed accidental or surgical trauma. Compared with fully sensitive control organisms, microbes infecting half the patients were resistant to penicillin. The prognosis of abscess of the CNS is grave, and the microbiological findings have important consequences for treatment. Prompt inoculation of specimens to culture plates and prompt incubation are mandatory if bacteria are to be cultured. Inhibitors of antimicrobial agents should be added to culture media if antibiotics have been administered. Provided that the site of the abscess and the antecedent history are ascertainable, the neurosurgeon should be able to start appropriate treatment while awaiting the results of culture.     

Mortality among patients with hypertension from 1995 to 2005: a population-based study

Background

We have reported that the prevalence of diagnosed hypertension increased by 60% from 1995 to 2005 in Ontario. In the present study, we asked whether this increase is explained by a decrease in the mortality rate.

Methods

We performed a population-based cohort study using linked administrative data for Ontario, a Canadian province with over 12 million residents. We identified prevalent cases of hypertension using a validated case-definition algorithm for hypertension, and we examined trends in mortality from 1995 to 2005 among adults aged 20 years and older with hypertension.

Results

The age-and sex-adjusted mortality among patients with hypertension decreased from 11.3 per 1000 people in 1995 to 9.6 per 1000 in 2005 (p < 0.001), which is a relative reduction of 15.5%. We found that the relative decrease in age-adjusted mortality was higher among men than among women (–22.2% v. –7.3%, p < 0.001).

Interpretation

Mortality rates among patients with hypertension have decreased. Along with an increasing incidence, decreased mortality rates may contribute to the increased prevalence of diagnosed hypertension. Sex-related discrepancies in the reduction of mortality warrant further investigation.High blood pressure is the leading risk factor for mortality around the world.^1,2 Over a decade ago, the Canadian Heart Health Survey reported that 42% of Canadian adults with hypertension were unaware that they had the condition and that only 16% of cases were treated and controlled.³ More recent studies in the United States⁴ and England⁵ have reported improved awareness, treatment and control among adults with hypertension. In addition, increased initiation of hypertensive medications among elderly patients⁶ and increased use of polytherapy for treating hypertension have been reported.⁷ Given that blood pressure control has been shown to reduce mortality, one might expect that enhanced awareness and treatment of hypertension has led to improvements in mortality among patients with this condition. Greater survival of patients with hypertension would contribute to an overall increase in the prevalence of hypertension.In another article in this issue of CMAJ, we report that the prevalence of diagnosed hypertension among adults increased by 60% from 1995 to 2005, which greatly surpassed prior projections for the developed world.⁸ Previous projections may have underestimated prevalence⁹ because researchers did not adequately account for the contribution of increased survival. Indeed, the increased prevalence cannot be explained by increased incidence alone, because the incidence of hypertension increased by 25.7% between 1997 and 2004 whereas prevalence increased by 35.5% during that same period. In the present study, our objective was to examine the mortality rates among patients with hypertension to determine whether declining mortality also contributed to the rising prevalence of hypertension.     

New approaches in the study of the neuroplasticity process in patients with central nervous system lesions

Methods that, on the one hand, can ensure patient’s mobility and, on the other hand, activate afferent inputs are the main in the rehabilitation treatment. Recent studies have shown that plasticity is the structural basis of recovery after central nervous system lesions. Reorganization of cortical areas, increase in the efficiency of the functioning of preserved structures; and active use of alternative ascending pathways, e.g., intensification of afferent input, constitute the anatomical basis of plasticity. However, sensory correction methods, without accounting of functional condition of patients, may lead to the formation of pathological symptoms: spasticity, hyperreflexia, etc. So, the main aim is to study adequate management of the neuroplasticity process. This problem cannot be solved without modern methods of neuroimaging and brain mapping. The new approach for the study of cortical mechanisms of neuroplasticity, responsible for locomotion, was developed in the present study. This approach is an integrated use of functional magnetic resonance imaging (fMRI) and navigation transcranial magnetic stimulation (nTMS). It has been shown that vast fMRI activation area in the first and second sensorimotor areas emerges with a passive sensorimotor paradigm usage that imitates backing load during walking. The Korvit mechanical stimulator of backing zones of footsteps is used to create this paradigm. The nTMS examination used after fMRI helps to localize motor representation of muscles which control locomotion more accurately. We assume that the new approach can be used for studying the neuroplasticity process and assessing neuroplasticity changes when taking rehabilitation measures to restore and correct the walking process.     

Congenital central nervous system malformations and vinyl chloride monomer exposure: a community study

Incidence rates for central nervous system (CNS) malformations in infants born to residents of Kanawha County, West Virginia, 1970-1974, were significantly higher than comparable United States rates during those years. Since Kanawha County contains a polyvinyl chloride (PVC) polymerization plant, a case-control study was conducted on the possible relationship between the occurrence of CNS defects and parental occupational or residential exposure to vinyl chloride monomer emissions from this plant. No relationship with parental occupation was found. While a tendency was noted for residences of case families to be located in an area northeast of the plant, this observation did not entirely correlate with existing data on local patterns of wind direction and air pollution.     

前庭代偿：研究中枢神经系统可塑性的一个理想模型

前庭代偿是一个研究神经系统损伤后机制修复和替代的理想模型,这个模型在中枢神经系统可塑性和机能恢复的研究机具有普遍意义,本文综述了有关前庭代偿的电生理学,生物化学和分子神经生物学的研究现状,还特别讨论了在前庭代偿中神经生长相关蛋白（ＧＡＰ－４３）ｍＲＮＡ的表达以及银杏叶提取物在前庭代偿过程中的促进作用。     

High diversity of poliovirus strains isolated from the central nervous system from patients with vaccine-associated paralytic poliomyelitis.

To establish the etiology of vaccine-associated paralytic poliomyelitis (VAPP), isolates from the central nervous system (CNS) from eight patients with VAPP were compared with stool isolates from the same patients. The vaccine (Sabin) origin was checked for all of the available isolates. Unique and similar strains were recovered from paired stool and CNS samples for five of the eight VAPP cases and the three wild-type cases included in the study. In the remaining three VAPP cases, the stool samples and, in one case, the CNS samples contained mixtures of strains. In two of these cases an equivalent of the CNS isolate was found among the strains separated by plaque purification from stool mixtures, and in one case different strains were isolated from CNS and stool. This shows that the stool isolate in VAPP might not be always representative of the etiologic agent of the neurological disease. A wide variety of poliovirus vaccine genomic structures appeared to be implicated in the etiology of VAPP. Of nine CNS vaccine-derived strains, four were nonrecombinant and five were recombinant (vaccine/vaccine or even vaccine/nonvaccine). The neuropathogenic potential of the isolates was evaluated in transgenic mice sensitive to poliovirus. All of the CNS-isolated strains lost the attenuated phenotype of the Sabin strains. However, for half of them, the neurovirulence was lower than expected, suggesting that the degree of neurovirulence for transgenic mice is not necessarily correlated with the neuropathogenicity in humans.     

Incidence,mortality and outcome of meningiomas: A population-based study from Germany

BackgroundMeningiomas are mostly benign tumors that originate from the coverings of the brain and spinal cord. Compared to malignant glial tumors, meningiomas are relatively understudied with regard to their risk factors and epidemiology. In particular, population-based data on cancer burden and patient outcomes are scant.MethodsPopulation-based data from Saarland, a federal state in South-Western Germany, were used; the data included 992 patients diagnosed with a first meningioma between 2000 and 2015. Incidence and mortality rates—as well as estimates of observed and relative survival and cumulative incidence of tumor recurrence up to 10 years after diagnosis—were derived by sex, age, WHO grade, and whether or not the patient had undergone surgery.ResultsThis population-based study not only included patients treated in the regional university hospital but also those treated elsewhere or patients without any surgical treatment. The mean age of the patients at diagnosis was 63 years, and 70%, 28% and 3% had WHO grade I, II and III meningiomas, respectively. Ten-year observed and relative survival of all patients combined was 72% and 91% respectively. Tumor-related mortality varied by sex and increased with age at diagnosis and the WHO grade of the tumor. The overall 10-year cumulative incidence of meningioma recurrence was 9%.ConclusionThis analysis represents the first modern population-based analysis of meningioma incidence and mortality and outcomes of patients with such neoplasms in Germany. Derived from an unselected sample of patients, this study may fill a hitherto existing gap in the literature on meningiomas.