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Receipt of Electroconvulsive Therapy and Subsequent Development of Amyotrophic Lateral Sclerosis: A Cohort Study
Abstract
We investigated the potential relationship between receipt of electroconvulsive therapy (ECT) and development of amyotrophic lateral sclerosis (ALS). We conducted a cohort study using a sample of more than one million beneficiaries enrolled in the U.S. Medicare health insurance program from 1997 to 2017. Using time-varying proportional hazard modeling, we compared ALS occurrence among patients diagnosed with psychiatric conditions who received ECT to ALS occurrence among patients diagnosed with psychiatric conditions but who did not receive ECT. We observed moderately increased, but imprecise, hazard ratios (HR) for ALS following ECT (HR = 1.39, 95% confidence interval [CI]: 0.69-2.80). A statistically significant increase in the HR of ALS was observed among those who received more than 10 ECT treatments (>10 treatments, HR = 2.24, 95% CI: 1.00-5.01), compared to those receiving no ECT, with an even stronger association observed among subjects older than 65 years (HR = 3.03, 95% CI: 1.13-8.10). No monotonic exposure-response relationship was detected in categorical analyses. Our results provide weak support for the hypothesis that receipt of ECT increases the risk of developing ALS. Additional studies in larger populations, or in populations where ECT is more common, will be needed to refute or confirm an association between receipt of ECT and subsequent development of ALS. Bioelectromagnetics. 43:81-89, 2022. © 2021 Bioelectromagnetics Society.
... • ECT recipients have more than double the rate of subsequently developing amyotrophic lateral sclerosis before age 65 and triple the rate of ALS after the age 65. 16 • People with chronic exposure to pulsed high electric fields have greater rates of subsequently developing neurodegenerative conditions 17 H. Dr. Bennet Omalu, Neuropathologist who first identified Chronic Traumatic Encephalopathy in American Football players stated that "repetitive head trauma causing functional injuries are not readily seen on standard scans" and "neuropathology of electrical injury as well as the neuropathology of people with a history of electroconvulsive therapy is well recognized as causing extensive functional changes to brain activity and should be considered in the context of both electrical injury and repetitive electrical trauma to the head because natural laws governing electricity aren't changed based on the intent of medical administration." ...
... 2, 3 The registry was not created. So in 2022, after examining twenty years of Medicare data, researchers discovered people with a history of just 10 ECT treatments, have more than double the risk of developing ALS before age 65; That risk triples, after age 65. 4 Two American manufacturers make Connecticut's ECT devices: MECTA and Somatics. Both face multiple pending lawsuits for causing permeant brain damage. ...
Testimony opposing CT SB 898 to extend forced electroconvulsive therapy (ECT) based on Long-Term Consequences of Electroconvulsive Therapy/Electrical Injury's neurological sequalae's association with neurodegenerative diseases.
Objective: Many thousands of people still receive electroconvulsive therapy but it remains highly contested. A recent audit of the United Kingdom patient information leaflets found multiple inaccuracies and omissions, minimizing risks and exaggerating benefits (e.g., only six leaflets mentioned cardiovascular events). This study reports efforts to improve accuracy for patients and families. Methods: Letters were sent twice to managers of all 51 United Kingdom National Health Service trusts (regional bodies which deliver most health care) detailing the audit’s findings and the accuracy of their own trust’s leaflet, also asking what changes would be undertaken. Results: Only nine trusts responded and three committed to improvements. The Royal College of Psychiatrists released a slightly better but still highly misleading information sheet. Efforts to engage government and all other relevant United Kingdom bodies failed. Conclusions: Trusts are unwilling to correct misinformation/ensure balanced information.
Objectives:
To evaluate the accuracy of patient information leaflets about electroconvulsive therapy (ECT) used in Northern Ireland, Scotland and Wales, and their compliance with the principle of informed consent.
Design and methods:
To replicate an audit in England, Freedom of Information Act requests were sent to the 26 providers of ECT for their ECT patient information leaflet. These were scored, by two independent raters, on the same 40-item accuracy measure used in the England audit.
Results:
The number of accurate statements (out of a possible 29) ranged from seven to 20, with a mean of 16.9. The most frequently omitted statements included: cardiovascular risks (mentioned by five leaflets), that it is not known how ECT works (3), risk of mortality (2), risks from multiple general anaesthetic procedures (2), how to access a legal advocate (2) and that that there is no evidence of long-term benefits (1). The leaflets made between six and nine inaccurate statements (out of 11) with a mean of 7.0. Nineteen minimised memory loss, blamed the memory loss on depression, claimed that ECT is the 'most effective treatment' and asserted it has very high response rates without mentioning similar placebo response rates. All 23 leaflets wrongly told patients that ECT saves lives.
Conclusions:
Electroconvulsive therapy information leaflets in these three nations are barely more accurate than those in England and do not comply with the ethical principle of informed consent. Patients and families across the UK are systematically being misled about the risks they are taking and the limited nature of ECT's benefits.
Original research discussing acquired communication disorders caused by electrical trauma which pose unique communication barriers due to their evolving symptom manifestation. As the person ages away from the initial injury, communication barriers can become more pronounced with age.
This presentation provides details explaining how electrical trauma, repeated electrical trauma and lengthy exposure to other forms of non-ionizing radiation can impact speech and communication. Following both UK's National Radiological Protection Board and United States Gulf War Hearing recommendations to study electroconvulsive therapy recipients to better understand the heterogeneity of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. I present four different case studies: Functional NeuroCognitive Imaging results and videos of ECT recipients now living with the neurological sequela of electrical injury which impacts speech and communication. It provides insights into the potential interventions which successfully work for the presenter who lives with speech and communication disorders as a result of chronic electroconvulsive therapy. It identifies strategies to make alternative augmentative communication (AAC) less fatiguing for people who live with a history of chronic exposure to non-ionizing radiation. The presentation concludes with ideas for future research.
-Non-ionizing radiation exposures and subsequent neurodegenerative diseases (Progressive supranuclear palsy and Myoneural Disorders: Amyotrophic Lateral Sclerosis, Motor Neuron Disease and Muscular Sclerosis).
-Immediate and delayed consequences of Electrical Injury/Electromagnetic injury
-Repetitive mild to moderate Traumatic Brain Injuries
-Cognitive communication disorder
-Anoxia/Hypoxia
-Trigeminal, vagal and other cranial nerve dysfunction.
-Electroporation
-Motor Neuron Dysfunction/Motor Neuron Loss
-Demyelination
-Episodic Paroxysmal Neuromuscular Disorders
-Acquired Channelopathies
-Thiols
-Aphasia
-Verbal Apraxia
-Dysarthria, Anarthria
-Preserving residual voice
-Barriers to accessing AAC
-Voice Banking
-AAC Recommendations
The presentation is available with 1.0 CEU through "AAC in the Cloud" website (https://presenters.aacconference.com/videos/UXpVd1FUSXk=)
In a New Zealand population-based case-control study we assessed associations with occupational exposure to electric shocks, extremely low-frequency magnetic fields (ELF-MF) and motor neurone disease using job-exposure matrices to assess exposure. Participants were recruited between 2013 and 2016. Associations with ever/never, duration, and cumulative exposure were assessed using logistic regression adjusted for age, sex, ethnicity, socioeconomic status, education, smoking, alcohol consumption, sports, head or spine injury and solvents, and mutually adjusted for the other exposure. All analyses were repeated stratified by sex. An elevated risk was observed for having ever worked in a job with potential for electric shocks (odds ratio (OR)=1.35, 95% confidence interval (CI): 0.98, 1.86), with the strongest association for the highest level of exposure (OR=2.01, 95%CI: 1.31, 3.09). Analysis by duration suggested a non-linear association: risk was increased for both short-duration (<3 years) (OR= 4.69, 95%CI: 2.25, 9.77) and long-duration in a job with high level of electric shock exposure (>24 years; OR=1.88; 95%CI: 1.05, 3.36), with less pronounced associations for intermediate durations. No association with ELF-MF was found. Our findings provide support for an association between occupational exposure to electric shocks and motor neurone disease but did not show associations with exposure to work-related ELF-MF.
Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with still unknown etiology. We aimed at investigating the association between environmental and occupational factors with ALS risk. Methods: We performed a population-based case-control study in four Italian provinces (Catania, Modena, Novara, and Reggio Emilia) by administration of tailored questionnaires to ALS cases (n = 95) and randomly selected population referents (n = 135). We estimated ALS risk by calculating the odds ratio (OR) with its 95% confidence interval (CI) using an unconditional logistic regression model. Results: We found a positive association with disease risk for history of occupation in the agricultural sector (OR = 2.09, 95% CI 0.79–7.54), especially for longer than 10 years (OR = 2.72, 95% 1.02–7.20). Overall occupational exposure to solvents also suggested a positive association, especially for thinners (OR = 2.27, 95% CI 1.14–4.54) and paint removers (OR = 2.01, 95% CI 0.90–4.48). Both occupational and environmental exposure to electromagnetic fields show a slightly increased risk with OR = 1.69 (95% CI 0.70–4.09) and 2.41 (95% CI 1.13–5.12), respectively. Occupational but not environmental exposure to pesticides (OR = 1.22, 95% CI 0.63–2.37), particularly fungicides, and exposure to metals (OR = 4.20, 95% CI 1.88–9.38), particularly lead, mercury, and selenium, showed an imprecise but positive association. Finally, there was an indication of increased risk for living in proximity to water bodies. Conclusions: Despite the caution that needs to be used due to some study limitations, such as the low number of exposed subjects and the possibility of recall bias, these results suggest the potential role of some environmental and occupational factors in ALS etiology.
Background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease of the motor neurons. The etiology of ALS remains largely unknown, particularly with reference to the potential environmental determinants. Methods: We performed a population-based case-control study in four provinces from both Northern and Southern Italy in order to assess non-genetic ALS risk factors by collecting through tailored questionnaires information about clinical and lifestyle factors. We estimated ALS risk by calculating odds ratio (OR) with its 95% confidence interval (CI) using unconditional logistic regression models adjusted for sex, age and educational attainment. Results: We recruited 230 participants (95 cases and 135 controls). We found a possible positive association of ALS risk with trauma, particularly head trauma (OR = 2.61, 95% CI 1.19–5.72), electric shock (OR = 2.09, 95% CI 0.62–7.06), and some sports, although at a competitive level only. In addition, our results suggest an increased risk for subjects reporting use of private wells for drinking water (OR = 1.38, 95% CI 0.73–2.27) and for use of herbicides during gardening (OR = 1.95, 95% CI 0.88–2.27). Conversely, there was a suggestion of an inverse association with overall fish consumption (OR = 0.27, 95% CI 0.12–0.60), but with no dose-response relation. Consumption of some dietary supplements, namely those containing amino acids and, in the Southern Italy population, vitamins and minerals such as selenium, seemed associated with a statistically imprecise increased risk. Conclusions: Our results suggest a potential etiologic role a number of clinical and lifestyle factors with ALS risk. However, caution is needed due to some study limitations. These include the small sample size and the low number of exposed subjects, which affect statistical precision of risk estimates, the potential for exposure misclassification, and the uncertainties about mechanisms underpinning the possible association between these factors and disease risk.
Objectives: To carry out an integrated and stratified meta-analysis on occupational exposure to electromagnetic fields (EMFs), metals and pesticides and its effects on amyotrophic lateral sclerosis (ALS) and Parkinson’s and Alzheimer’s disease, and investigate the possibility of publication bias. Methods: In the current study, we updated our recently published meta-analyses on occupational exposures in relation to ALS, Alzheimer’s and Parkinson’s disease. Based on 66 original publications of good scientific epidemiological standard, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines, we analysed subgroups by carrying out stratified meta-analyses on publication year, statistical precision of the relative risk (RR) estimates, inspection of the funnel plots and test of bias. Results: Based on 19 studies the weighted RR for occupational exposure to EMFs was 1.26 (95% confidence interval (CI) 1.07–1.50) for ALS, 1.33 (95% CI 1.07–1.64) for Alzheimer’s disease and 1.02 (95% CI 0.83–1.26) for Parkinson’s disease. Thirty-one studies concerned occupational exposure to pesticides and the weighted RR was 1.35 (95% CI 1.02–1.79) for ALS, 1.50 (95% CI 0.98–2.29) for Alzheimer’s disease and 1.66 (95% CI 1.42–1.94) for Parkinson’s disease. Finally, 14 studies concerned occupational exposure to metals and only exposure to lead (five studies) involved an elevated risk for ALS or Parkinson’s disease and the weighted RR was 1.57 (95% CI 1.11–2.20). The weighted RR for all the non-lead exposures was 0.97 (95% CI 0.88–1.06). Conclusions: Exposure to pesticides increased the risk of getting the mentioned neurodegenerative diseases by at least 50%. Exposure to lead was only studied for ALS and Parkinson’s disease and involved 50% increased risk. Occupational exposure to EMFs seemed to involve some 10% increase in risk for ALS and Alzheimer’s disease only.
Amyotrophic lateral sclerosis is a neurodegenerative disease predominantly affecting upper and lower motor neurons, resulting in progressive paralysis and death from respiratory failure within 2 to 3 years. The peak age of onset is 55 to 70 years, with a male predominance. The causes of amyotrophic lateral sclerosis are only partly known, but they include some environmental risk factors as well as several genes that have been identified as harbouring disease-associated variation. Here we review the nature, epidemiology, genetic associations, and environmental exposures associated with amyotrophic lateral sclerosis.
Since the 1930s, the Department of Psychiatry and Psychotherapy at Semmelweis University (DPPSU) in Budapest has played a leading role in convulsive therapy in Hungary. The aim of this study was to describe the pattern of ECT use at the DPPSU over an 11-year period.
Analysis of the medical notes of all patients treated with ECT in this academic centre between 1999 and 2009.
During the study period, 28,230 patients were admitted to the DPPSU, of whom 457 (1.6%) received ECT. More than 50% of patients receiving ECT were diagnosed with schizophrenia. The percentage of female patients receiving ECT significantly exceeded that of the male patients, above what was expected in view of the diagnostic mix.
The data indicate that in the first decade of the 21(th) century, ECT use shows a declining tendency in this Hungarian academic centre. The mean number of treatment sessions was relatively low and nearly the same across diagnostic groups. ECT was mainly used as a last resort for treatment-resistant patients. In the majority of cases, bifronto-temporal brief pulse stimulation was applied. Seizures were monitored with EEG and EMG.
We have performed a systematic review to summarize current knowledge concerning factors related to survival in ALS and to evaluate the implications of these data for clinical trials design. The median survival time from onset to death ranges from 20 to 48 months, but 10-20% of ALS patients have a survival longer than 10 years. Older age and bulbar onset are consistently reported to have a worse outcome. There are conflicting data on gender, diagnostic delay and El Escorial criteria. The rate of symptom progression was revealed to be an independent prognostic factor. Psychosocial factors, FTD, nutritional status, and respiratory function are also related to ALS outcome. The effect of enteral nutrition on survival is still unclear, while NIPPV has been found to improve survival. There are no well established biological markers of progression, although some are likely to emerge in the near future. These findings have relevant implications for the design of future trials. Randomization, besides the type of onset, should take into account age, respiratory status at entry, and a measure of disease progression pre-entry. Alternative trial designs can include the use of natural history controls, the so-called minimization method for treatment allocation, and the futility approach.
Conditional logistic regression was developed to avoid "sparse-data" biases that can arise in ordinary logistic regression analysis. Nonetheless, it is a large-sample method that can exhibit considerable bias when certain types of matched sets are infrequent or when the model contains too many parameters. Sparse-data bias can cause misleading inferences about confounding, effect modification, dose response, and induction periods, and can interact with other biases. In this paper, the authors describe these problems in the context of matched case-control analysis and provide examples from a study of electrical wiring and childhood leukemia and a study of diet and glioma. The same problems can arise in any likelihood-based analysis, including ordinary logistic regression. The problems can be detected by careful inspection of data and by examining the sensitivity of estimates to category boundaries, variables in the model, and transformations of those variables. One can also apply various bias corrections or turn to methods less sensitive to sparse data than conditional likelihood, such as Bayesian and empirical-Bayes (hierarchical regression) methods.
Exposure to extremely low frequency magnetic fields (ELF-MF) and electric shocks occurs in many workplaces and occupations but it is unclear whether any of these exposures cause Amyotrophic lateral sclerosis (ALS). The aim of this systematic review and meta-analysis is to explore whether occupational exposure to ELF-MF and/or electric shocks are risk factor for ALS. We searched PubMed, Embase, and Web of Science databases up to the end of 2019. Pooled risk estimates were calculated using random-effects meta-analysis including exploration of the sources of heterogeneity between studies and publication bias. Twenty-seven publications fulfilled the inclusion criteria. We found a weak, significant, association between occupational exposure to ELF-MF and the risk of ALS (RRPooled estimate: 1.20; 95%CI: 1.05, 1.38) with moderate to high heterogeneity (I2=66.3%) and indication of publication bias (PEgger's test=0.03). No association was observed between occupational exposure to electric shocks and risk of ALS (RRPooled estimate: 0.97; 95%CI: 0.80, 1.17) with high heterogeneity (I2=80.5%), and little indication for publication bias (PEgger's test=0.24). The findings indicate that occupational exposure to ELF-MF, but not electric shocks, might be a risk factor for ALS. However, given the moderate to high heterogeneity and potential publication bias, the results should be interpreted with caution.
We explored the associations of occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and electric shocks with the risk of amyotrophic lateral sclerosis (ALS) in a pooled case-control study (European Multidisciplinary ALS Network Identification to Cure Motor Neurone Degeneration (Euro-MOTOR)) of data from 3 European countries. ALS patients and population-based controls were recruited in Ireland, Italy, and the Netherlands between 2010 and 2015. Lifetime occupational and lifestyle histories were obtained using structured questionnaires. We applied previously developed job exposure matrices assigning exposure levels to ELF-MF and potential for electric shocks. Odds ratios and 95% confidence intervals were estimated by means of logistic regression for exposure to either ELF-MF or electric shocks, adjusted for age, sex, study center, education, smoking, and alcohol consumption and for the respective other exposure. Complete occupational histories and information on confounding variables were available for 1,323 clinically confirmed ALS cases and 2,704 controls. Both ever having had exposure to ELF-MF above the background level (odds ratio = 1.16, 95% confidence interval: 1.01, 1.33) and ever having had potential exposure above background for electric shocks (odds ratio = 1.23, 95% confidence interval: 1.05, 1.43) were associated with ALS. Adjustment for the respective other exposure resulted in similar risk estimates. Heterogeneity in risks across study centers was significant for both exposures. Our findings support possible independent associations of occupational exposure to ELF-MF and electric shocks with the risk of ALS.
We performed a meta-analysis to examine associations of occupational exposure to extremely-low frequency magnetic fields (ELF-MF) with amyotrophic lateral sclerosis (ALS). Epidemiologic studies were identified in EMBASE and MEDLINE, in reference lists and a specialist database. We included studies that reported risk estimates of ALS in association with occupational ELF-MF exposure. Summary relative risks (RR) or odds ratios (OR) were obtained with random effect meta-analysis, and analyses were stratified by type of exposure assessment. This was done to evaluate whether observed heterogeneity between studies could be explained with differences in the way the exposure had been determined. We included 20 studies in our meta-analysis. Overall, studies reported a slightly increased risk of ALS in those exposed to higher levels of ELF-MF compared to lower levels with a summary RR (sRR) of 1.14 (95% Confidence Interval [CI] 1.00–1.30) and for workers in electrical occupations (sRR 1.41, CI 1.05–1.92), but with large heterogeneity between studies (I2 > 70%). Self-reported exposure or occupations determined from death certificates did not show increased risks. Highest-longest types of exposure translated into increased risks of ALS if the studies had evaluated the whole occupational history, in contrast to evaluating only few points in time (e.g., from census records); sRR were 1.89 (CI 1.31–2.73, I2 0%) and 1.06 (CI 0.75–1.57, I2 76%), respectively. In this meta-analysis, we observed an increased risk of ALS in workers occupationally exposed to ELF-MF. Results of studies depended on the quality of the exposure assessment. Bioelectromagnetics.
As our knowledge of amyotrophic lateral sclerosis (ALS) increases, the salient question has become: Is ALS a single disease or a group of diseases with a final common pathway? Traditionally, ALS has been defined as a rapidly progressive neurodegenerative disorder that affects the large motor neurons of the brain and spinal cord. It presents with an upper or lower motor neuron pattern of weakness but progresses to include all motor neurons (upper and lower, bulbar, cervical, thoracic, and lumbar). Cognition was thought to be affected in only a small subset of patients with ALS. The primary causation theory was that ALS was the result of a single common exposure or genetic mutation, and the primary pathologic finding was simple motor neuron degeneration. Recent studies on the genetics of ALS have changed this view.
Objective:
To prospectively study suspected occupational risk factors for amyotrophic lateral sclerosis (ALS).
Methods:
For this case-cohort analysis within the prospective Netherlands Cohort Study, 58?279 men and 62?573 women aged 55-69 years at enrolment in 1986 were followed up for 17.3 years on ALS mortality. Information on occupational history and potential confounders were collected at baseline through a self-administered questionnaire and entered for a random subcohort (2092 men and 2074 women) and ALS deaths (76 men and 60 women). Occupational exposure to solvents, pesticides, metals, extremely low frequency magnetic fields (ELF-MFs) and electrical shocks was estimated by means of job exposure matrices (JEMs). Associations between ever/never occupationally exposed and cumulative exposure and ALS mortality were analysed by gender using Cox regression.
Results:
Occupational exposure to ELF-MF showed a possible association with ALS mortality among men: HR for ever holding a job with high exposure versus background 2.19 (95% (CI): 1.02 to 4.73) and HR for the highest tertile of cumulative exposure versus background 1.93 (95% CI 1.05 to 3.55).
Interpretation:
These results strengthen the evidence suggesting a positive association between ELF-MF exposure and ALS. We did not replicate earlier positive findings for other occupational exposures.
Effects of treatment or other exposure on outcome events are commonly measured by ratios of risks, rates, or odds. Adjusted versions of these measures are usually estimated by maximum likelihood regression (eg, logistic, Poisson, or Cox modelling). But resulting estimates of effect measures can have serious bias when the data lack adequate case numbers for some combination of exposure and outcome levels. This bias can occur even in quite large datasets and is hence often termed sparse data bias. The bias can arise or be worsened by regression adjustment for potentially confounding variables; in the extreme, the resulting estimates could be impossibly huge or even infinite values that are meaningless artefacts of data sparsity. Such estimate inflation might be obvious in light of background information, but is rarely noted let alone accounted for in research reports. We outline simple methods for detecting and dealing with the problem focusing especially on penalised estimation, which can be easily performed with common software packages.
This book provides the foundation for conducting rigorous epidemiologic and clinical research on neurologic disorders. The book has three parts, each emphasizing the unique aspects of studying neurologic disorders. The first focuses on classic principles of epidemiologic and clinical research, including study design, sources of study bias, and methods for assessing the role of environmental and genetic factors in neurologic disorders. The second part covers each of the major neurologic disorders, with an emphasis on the methodologic aspects of studying these disorders and discussion of future research directions. The third part is devoted to clinical and translational research methods, including the design and conduct of clinical trials and prognostic studies, as well as the principles of health services research and evidence-based medicine. Throughout the book, the principles of neuroepidemiology are illustrated with examples from published studies.
Background: Amyotrophic lateral sclerosis (ALS) has been consistently related to "electric occupations," but associations with magnetic field levels were generally weaker than those with electrical occupations. Exposure to electric shock has been suggested as a possible explanation. Furthermore, studies were generally based on mortality or prevalence of ALS, and studies often had limited statistical power. Methods: Using two electric shock and three magnetic field jobexposure matrices, we evaluated the relationship of occupational magnetic fields, electric shocks, electric occupations, and incident ALS in a large population-based nested case-control study in Sweden. Subanalyses, specified a priori, were performed for subjects by gender and by age (less than and more than 65 years). Results: Overall, we did not observe any associations between occupational magnetic field or electric shock exposure and ALS. For individuals less than 65 years old, high electric shock exposure was associated with an odds ratio (OR) of 1.22 (95% confidence interval [CI] = 1.03, 1.43). The corresponding result for the age group 65 years or older was OR = 0.92 (95% CI = 0.81, 1.05). Results were similar regardless which job exposure matrices, exposure definitions, or cutpoints were used. For electric occupations, ORs were close to unity, regardless of age. For welders, no association was observed overall, although for welders <65 years the OR was 1.52 (95% CI = 1.05, 2.21). Conclusions: In this very large population-based study based on incident ALS case subjects, we did not confirm previous observations of higher risk of ALS in electrical occupations, and provided only weak support for associations between electric shocks and ALS.
With explanatory covariates, the standard analysis for competing risks data involves modeling the cause-specific hazard functions via a proportional hazards assumption. Unfortunately, the cause-specific hazard function does not have a direct interpretation in terms of survival probabilities for the particular failure type. In recent years many clinicians have begun using the cumulative incidence function, the marginal failure probabilities for a particular cause, which is intuitively appealing and more easily explained to the nonstatistician. The cumulative incidence is especially relevant in cost-effectiveness analyses in which the survival probabilities are needed to determine treatment utility. Previously, authors have considered methods for combining estimates of the cause-specific hazard functions under the proportional hazards formulation. However, these methods do not allow the analyst to directly assess the effect of a covariate on the marginal probability function. In this article we propose a novel semiparametric proportional hazards model for the subdistribution. Using the partial likelihood principle and weighting techniques, we derive estimation and inference procedures for the finite-dimensional regression parameter under a variety of censoring scenarios. We give a uniformly consistent estimator for the predicted cumulative incidence for an individual with certain covariates; confidence intervals and bands can be obtained analytically or with an easy-to-implement simulation technique. To contrast the two approaches, we analyze a dataset from a breast cancer clinical trial under both models.
Amyotrophic lateral sclerosis (ALS) has been associated with exposures in so-called 'electrical occupations'. It is unclear if this possible link may be explained by exposure to extremely low-frequency magnetic fields (ELF-MF) or by electrical shocks. We evaluated ALS mortality in 2000-2008 and exposure to ELF-MF and electrical shocks in the Swiss National Cohort, using job exposure matrices for occupations at censuses 1990 and 2000. We compared 2.2 million workers with high or medium vs. low exposure to ELF-MF and electrical shocks using Cox proportional hazard models. Results showed that mortality from ALS was higher in people who had medium or high ELF-MF exposure in both censuses (HR 1.55 (95% CI 1.11-2.15)), but closer to unity for electrical shocks (HR 1.17 (95% CI 0.83-1.65)). When both exposures were included in the same model, the HR for ELF-MF changed little (HR 1.56), but the HR for electric shocks was attenuated to 0.97. In conclusion, there was an association between exposure to ELF-MF and mortality from ALS among workers with a higher likelihood of long-term exposure.
We investigated the relationship between occupational exposure to electric shocks (ES) and magnetic fields (MF) and amyotrophic lateral sclerosis (ALS) using 1991-1999 US mortality data. For each of the 5886 included ALS deaths, 10 controls-matched on sex-, age-, year- and region-were selected from among other deaths. Usual occupation as reported on death certificates was linked to job-exposure matrices for ES and MF. Education and electric occupations were associated with moderately increased ALS risks (odds ratio (OR)=1.85, 95% confidence interval (CI)=1.67, 2.04; OR=1.23, 95% CI=1.04, 1.47, respectively). For ES, ALS mortality OR were 0.73 (95% CI=0.67, 0.79) for high and 0.90 (95% CI=0.84, 0.97) for medium exposure compared with low exposure. For MF, ALS ORs were 1.09 (95% CI=1.00, 1.19) for high and 1.09 (95% CI=0.96, 1.23) for medium exposure as compared with low exposure. For electric occupations, ALS ORs were insensitive to adjustments for ES, MF or both. Consistent with previous publications, an association between electric occupations and ALS was observed. Findings do not support occupational exposure to ES or MF as an explanation.Journal of Exposure Science and Environmental Epidemiology advance online publication, 11 June 2014; doi:10.1038/jes.2014.39.
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease of motor neurons, resulting in worsening weakness of voluntary muscles until death from respiratory failure occurs after about 3 years. Although great advances have been made in our understanding of the genetic causes of ALS, the contribution of environmental factors has been more difficult to assess. Large-scale studies of the clinical patterns of ALS, individual histories preceding the onset of ALS, and the rates of ALS in different populations and groups have led to improved patient care, but have not yet revealed a replicable, definitive environmental risk factor. In this Review, we outline what is currently known of the environmental and genetic epidemiology of ALS, describe the current state of the art with respect to the different types of ALS, and explore whether ALS should be considered a single disease or a syndrome. We examine the relationship between genetic and environmental risk factors, and propose a disease model in which ALS is considered to be the result of environmental risks and time acting on a pre-existing genetic load, followed by an automatic, self-perpetuating decline to death.
Amyotrophic lateral sclerosis (ALS), first described by Jean-Martin Charcot in the 1870s, is an age-related disorder that leads to degeneration of motor neurons. The disease begins focally in the central nervous system and then spreads relentlessly. The clinical diagnosis, defined by progressive signs and symptoms of upper and lower motor neuron dysfunction, is confirmed by electromyography. Additional testing excludes other conditions. The disease is heterogeneous, but most patients die of respiratory muscle weakness less than 3 years from symptom-onset. Like other age-related neurodegenerative diseases, ALS has genetic and environmental triggers. Of the five to 10% of cases that are inherited, mutations have been discovered for a high proportion. In addition to genetic factors, age, tobacco use, and athleticism may contribute to sporadic ALS, but important etiologies are unidentified for most patients. Complex pathophysiological processes, including mitochondrial dysfunction, aggregation of misfolded protein, oxidative stress, excitotoxicity, inflammation and apoptosis, involve both motor neurons and surrounding glial cells. There is clinical and pathological overlap with other neurodegenerative diseases, particularly frontotemporal dementia. The mechanisms leading to disease propagation in the brain are a current focus of research. To date, one medication, riluzole, licensed in 1996, has been proved to prolong survival in ALS. Numerous clinical trials have so far been unable to identify another neuroprotective agent. Researchers now aim to slow disease progression by targeting known pathophysiological pathways or genetic defects. Current approaches are directed at muscle proteins such as Nogo, energetic balance, cell replacement, and abnormal gene products resulting from mutations. Until better understanding of the causes and mechanisms underlying progression lead to more robust neuroprotective agents, symptomatic therapies can extend life and improve quality of life. Palliative care programs such as hospice give emotional and physical support to patients and families throughout much of the disease course.
With explanatory covariates, the standard analysis for competing risks data involves modeling the cause-specific hazard functions via a proportional hazards assumption. Unfortunately, the cause-specific hazard function does not have a direct interpretation in terms of survival probabilities for the particular failure type. In recent years many clinicians have begun using the cumulative incidence function, the marginal failure probabilities for a particular cause, which is intuitively appealing and more easily explained to the nonstatistician. The cumulative incidence is especially relevant in cost-effectiveness analyses in which the survival probabilities are needed to determine treatment utility. Previously, authors have considered methods for combining estimates of the cause-specific hazard functions under the proportional hazards formulation. However, these methods do not allow the analyst to directly assess the effect of a covariate on the marginal probability function. In this article we propose a novel semiparametric proportional hazards model for the subdistribution. Using the partial likelihood principle and weighting techniques, we derive estimation and inference procedures for the finite-dimensional regression parameter under a variety of censoring scenarios. We give a uniformly consistent estimator for the predicted cumulative incidence for an individual with certain covariates; confidence intervals and bands can be obtained analytically or with an easy-to-implement simulation technique. To contrast the two approaches, we analyze a dataset from a breast cancer clinical trial under both models.
: Previous studies reported associations of occupational electric and magnetic fields (MF) with neurodegenerative diseases (NDDs). Results differ between studies using proxy exposure based on occupational titles and estimated MF levels. We conducted a meta-analysis of occupational MF NDD, primarily Alzheimer disease (AD), and motor neuron diseases (MNDs) studies.
: We identified 42 peer-reviewed publications and focused our analysis on study characteristics, exposure metrics, and publication bias.
: We found weak associations for occupational MF exposure proxies with AD and MND. Motor neuron disease risk was associated with occupational titles, whereas AD risk was associated with estimated MF levels. Results varied in study design, with dissimilar variation across diseases.
: Our results do not support MF as the explanation for observed associations between occupational titles and MND. Disease misclassification, particularly for AD, and imprecise exposure assessment affected most studies.
Objectives. The aim of the study was to document the present situation of electroconvulsive therapy (ECT) in Germany, compare its handling with regard to other industrialized countries and with regard to a survey 12 years ago. Methods. A questionnaire on the frequency and type of administration of ECT in 2008 was sent electronically to 423 psychiatric hospitals. As needed, up to five reminders were carried out by telephone. On this occasion, the question of whether ECT is administered, could be clarified for each hospital. Results. A total of 43% (183/423) of hospitals declared to administer ECT; 63% (115/183) reported nearly 20,000 treatments. A total incidence of 30,000 treatments performed on 2800 individual patients was estimated. This means that 3.4 patients per 10(5) inhabitants, 0.4‰ of all depressed patients, and about 1% of depressed inpatients, are treated with ECT in Germany. Conclusions. The frequency of application has increased during the last 12 years by a factor of more than 2.5 in Germany. In Western industrialized countries, numbers vary by a factor of more than 10 amongst the countries with a slow trend of equalization. The mode of implementation and the areas of conflict in which the therapy stands seem to be similar.
Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease of the human motor system. In this Seminar, we summarise current concepts about the origin of the disease, what predisposes patients to develop the disorder, and discuss why all cases of ALS are not the same. In the 150 years since Charcot originally described ALS, painfully slow progress has been made towards answering these questions. We focus on what is known about ALS and where research is heading-from the small steps of extending longevity, improving therapies, undertaking clinical trials, and compiling population registries to the overarching goals of establishing the measures that guard against onset and finding the triggers for this neurodegenerative disorder.
The occupational epidemiological literature on extremely low frequency electric and magnetic fields (EMF) and health encompasses a large number of studies of varying design and quality that have addressed many health outcomes, including various cancers, cardiovascular disease, depression and suicide, and neurodegenerative diseases, such as Alzheimer disease and amyotrophic lateral sclerosis (ALS). At a 2006 workshop we reviewed studies of occupational EMF exposure with an emphasis on methodological weaknesses, and proposed analytical ways to address some of these. We also developed research priorities that we hope will address remaining uncertainties. Broadly speaking, extensive epidemiological research conducted during the past 20 years on occupational EMF exposure does not indicate strong or consistent associations with cancer or any other health outcomes. Inconsistent results for many of the outcomes may be attributable to numerous shortcomings in the studies, most notably in exposure assessment. There is, however, no obvious correlation between exposure assessment quality and observed associations. Nevertheless, for future research, the highest priorities emerge in both the areas of exposure assessment and investigation of ALS. To better assess exposure, we call for the development of a more complete job-exposure matrix that combines job title, work environment and task, and an index of exposure to electric fields, magnetic fields, spark discharge, contact current, and other chemical and physical agents. For ALS, we propose an international collaborative study capable of illuminating a reported association with electrical occupations by disentangling the potential roles of electric shocks, magnetic fields and bias. Such a study will potentially lead to evidence-based measures to protect public health.
The authors conducted a study of 518 amyotrophic lateral sclerosis patients identified between 1977 and 1979 and 518 controls to investigate putative risk factors for this disease. Occupations at risk of electrical exposure were reported more often by patients (odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.4-13.0) as were electrical shocks producing unconsciousness (OR = 2.8, 95% CI = 1.0-9.9). Although an overall excess of physical trauma associated with unconsciousness was observed in the amyotrophic lateral sclerosis patients (OR = 1.6, 95% CI = 1.0-2.4), the effect was inversely associated with duration of the unconscious episodes, suggesting an effect of recall bias. Only slight differences were found for surgical traumata to the nervous system. Parkinsonism was reported more often among first degree relatives of cases (OR = 2.7, 95% CI = 1.1-7.6). The frequencies of prior poliomyelitis or other central nervous system diseases were similar for patients and controls. Occupational exposure to selected toxic substances was similar for patients and controls except for the manufacture of plastics (OR = 3.7, 95% CI = 1.0-20.5), although few details of these exposures were provided. No differences in occupations with exposure to animal skins or hides were observed.
To describe temporal trends of motor neuron disease (MND) mortality in the United States. Variations in MND by demographic variables of sex, age, geography, and race/ethnicity were evaluated to assess the possible explanations for observed trends.
Multiple-cause mortality files from the National Center for Health Statistics for the years 1969 through 1998 were searched for all United States death records with codes corresponding to MND. Age-adjusted mortality rates were calculated by sex, race/ethnicity, age, birth cohort, and place of death.
Overall MND mortality rates increased from 1.25 per 100,000 to 1.82 per 100,000, representing a 46% increase during the 30-year period. Rates among women increased by 60% and continue to rise. Rates among men rose by 35% during this period but have leveled off in the most recent decade evaluated. Mortality rates among African Americans and Hispanics were approximately 50% lower than rates among non-Hispanic whites. A southeast to northwest gradient was observed when rates were grouped by 12 geographic areas. MND mortality rates per 100,000 (and 95% CI) ranged from 2.22 (1.89 to 2.55) in the Northwest to 1.57 (1.44 to 1.71) in the Southeast.
Variations in motor neuron disease (MND) mortality by time, race/ethnicity, sex, and geography were consistent with the hypothesis that environmental exposures, combined with factors of genetic susceptibility, play a role in the development of MND.
To determine the characteristics of electroconvulsive therapy (ECT) practice in Australia.
From October 1, 2002 to February 29, 2004, a 29-item questionnaire was sent to 136 hospitals in Australia.
One hundred thirteen hospitals (83%) completed the questionnaire. Electroconvulsive therapy was available in 90 hospitals. A total of 7469 patients received 58,499 ECTs from 356 psychiatrists, which gives an average course length of 8.5 treatments. Electroconvulsive therapy use as assessed by the crude treated-person rate was 37.85 persons per 100,000 population per annum. Of the number of patients, 63.4% were women. Brief-pulse devices were used in all hospitals. Electroencephalogram monitoring was used routinely in 80 hospitals. Of the total number of ECT treatments, 82.3% were given to patients with major depression, 9.6% to patients with schizophrenia, 4.9% to patients with mania, and 1.7% to patients with catatonia. Patients who received ECT were in an age group older than 65 years (38.4%), followed by 45 to 64 years (28.3%), 25 to 44 years (26.3%), 18 to 24 years (6.9%), and less than 18 years (0.2%). Unmodified ECT was not used in any hospital. One thousand one hundred ninety-six patients received continuation ECT in 83 hospitals, and 1044 received maintenance ECT in 77 hospitals. There was no case of ECT-related death during a survey period. Only 31 hospitals rated their teaching program for medical students as acceptable to excellent, and for psychiatry residents, it was 58.
A proportional hazards model for the subdistribution of a competing risk
- Fine J
Clinical Manual of Electroconvulsive Therapy
- MV Mankad
- JL Beyer
- RD Weiner
- A Krystal