The matching method for treatment evaluation with selective participation and ineligibles

The matching method for treatment evaluation does not balance selective unobserved differences between treated and non-treated. We derive a simple correction term if there is an instrument that shifts the treatment probability to zero in specific cases. Within the same framework we also suggest a new test of the conditional independence assumption justifying matching. Policies with eligibility restrictions, where treatment is impossible if some variable exceeds a certain value, provide a natural application. In an empirical analysis, we exploit the age eligibility restriction in the Swedish Youth Practice subsidized work program for young unemployed, where compliance is imperfect among the young. Adjusting the matching estimator for selectivity changes the results towards making of subsidized work detrimental in moving individuals into employment.

The Matching Method for Treatment Evaluation with Selective Participation and Ineligibles

The matching method for treatment evaluation does not balance selective unobserved differences between treated and non-treated. We derive a simple correction term if there is an instrument that shifts the treatment probability to zero in specific cases. Policies with eligibility restrictions, where treatment is impossible if some variable exceeds a certain value, provide a natural application. In an empirical analysis, we first examine the performance of matching versus regression-discontinuity estimation in the sharp age-discontinuity design of the NDYP job search assistance program for young unemployed in the UK. Next, we exploit the age eligibility restriction in the Swedish Youth Practice subsidized work program for young unemployed, where compliance is imperfect among the young. Adjusting the matching estimator for selectivity changes the results towards ineffectiveness of subsidized work in moving individuals into employment.job search assistance, selection, regression discontinuity, treatment effect, policy evaluation, propensity score, subsidized work, youth unemployment

The matching method for treatment evaluation with selective participation and ineligibles

The matching method for treatment evaluation does not balance selective unobserved differences between treated and non-treated. We derive a simple correction term if there is an instrument that shifts the treatment probability to zero in specific cases. Policies with eligibility restrictions, where treatment is impossible if some variable exceeds a certain value, provide a natural application. In an empirical analysis, we first examine the performance of matching versus regression-discontinuity estimation in the sharp age-discontinuity design of the NDYP job search assistance program for young unemployed in the UK. Next, we exploit the age eligibility restriction in the Swedish Youth Practice subsidized work program for young unemployed, where compliance is imperfect among the young. Adjusting the matching estimator for selectivity changes the results towards inefectiveness of subsidized work in moving individuals into employment.Propensity score; policy evaluation; treatment effect; regression discontinuity; selection; job search assistance; subsidized work; youth unemployment

The Matching Method for Treatment Evaluation with Selective Participation and Ineligibles

The matching method for treatment evaluation does not balance selective unobserved differences between treated and non-treated. We derive a simple correction term if there is an instrument that shifts the treatment probability to zero in specific cases. Policies with eligibility restrictions, where treatment is impossible if some variable exceeds a certain value, provide a natural application. In an empirical analysis, we exploit the age eligibility restriction in the Swedish Youth Practice subsidized work program for young unemployed, where compliance is imperfect among the young. Adjusting the matching estimator for selectivity changes the results towards making subsidized work detrimental in moving individuals into employment.We also consider the eligibility change induced by the introduction of the program

Diversity in Alzheimer\u27s Disease Drug Trials: The Importance of Eligibility Criteria

INTRODUCTION: To generalize safety and efficacy findings, it is essential that diverse populations are well represented in Alzheimer\u27s disease (AD) drug trials. In this review, we aimed to investigate participant diversity in disease-modifying AD trials over time, and the frequencies of participant eligibility criteria. METHODS: A systematic review was performed using Medline, Embase, the Cochrane Library, and Clinicaltrials.gov, identifying 2247 records. RESULTS: In the 101 included AD trials, participants were predominantly White (median percentage: 94.7%, interquartile range: 81.0-96.7%); and this percentage showed no significant increase or decrease over time (2001-2019). Eligibility criteria such as exclusion of persons with psychiatric illness (78.2%), cardiovascular disease (71.3%) and cerebrovascular disease (68.3%), obligated caregiver attendance (80.2%), and specific Mini-Mental State Examination scores (90.1%; no significant increase/decrease over time) may have led to a disproportionate exclusion of ethnoracially diverse individuals. DISCUSSION: Ethnoracially diverse participants continue to be underrepresented in AD clinical trials. Several recommendations are provided to broaden eligibility criteria

Lithium carbonate in amyotrophic lateral sclerosis patients homozygous for the C-allele at SNP rs12608932 in UNC13A: protocol for a confirmatory, randomized, group-sequential, event-driven, double-blind, placebo-controlled trial

BackgroundGiven the large genetic heterogeneity in amyotrophic lateral sclerosis (ALS), it seems likely that genetic subgroups may benefit differently from treatment. An exploratory meta-analysis identified that patients homozygous for the C-allele at SNP rs12608932, a single nucleotide polymorphism in the gene UNC13A, had a statistically significant survival benefit when treated with lithium carbonate. We aim to confirm the efficacy of lithium carbonate on the time to death or respiratory insufficiency in patients with ALS homozygous for the C-allele at SNP rs12608932 in UNC13A. MethodsA randomized, group-sequential, event-driven, double-blind, placebo-controlled trial will be conducted in 15 sites across Europe and Australia. Patients will be genotyped for UNC13A; those homozygous for the C-allele at SNP rs12608932 will be eligible. Patients must have a diagnosis of ALS according to the revised El Escorial criteria, and a TRICALS risk-profile score between -6.0 and -2.0. An expected number of 1200 patients will be screened in order to enroll a target sample size of 171 patients. Patients will be randomly allocated in a 2:1 ratio to lithium carbonate or matching placebo, and treated for a maximum duration of 24 months. The primary endpoint is the time to death or respiratory insufficiency, whichever occurs first. Key secondary endpoints include functional decline, respiratory function, quality of life, tolerability, and safety. An interim analysis for futility and efficacy will be conducted after the occurrence of 41 events. DiscussionLithium carbonate has been proven to be safe and well-tolerated in patients with ALS. Given the favorable safety profile, the potential benefits are considered to outweigh the burden and risks associated with study participation. This study may provide conclusive evidence about the life-prolonging potential of lithium carbonate in a genetic ALS subgroup

Subchronic toxicity of Baltic herring oil and its fractions in the rat II: Clinical observations and toxicological parameters

This study aimed to increase the knowledge about the toxicity of fish-derived organohalogen pollutants in mammals. The strategy chosen was to separate organohalogen pollutants derived from Baltic herring (Clupea harengus) fillet, in order to obtain fractions with differing proportions of identified and unidentified halogenated pollutants, and to perform a subchronic toxicity study in rats, essentially according to the OECD guidelines, at three dose levels. Nordic Sea Iodda (Mallotus villosus) oil, with low levels of persistent organohalogen pollutants, was used as an additional control diet. The toxicological examination showed that exposure to Baltic herring oil and its fractions at dose levels corresponding to a human intake in the range of 1.6 to 34.4 kg Baltic herring per week resulted in minimal effects. The spectrum of effects was similar to that, which is observed after low-level exposure to pollutants such as chlorinated dibenzo-p-dioxins and dibenzofurans (CDD/F) and chlorinated biphenyls, despite the fact that these contaminants contribute to a minor part of the extractable organically bound chlorine (EOC1). The study confirmed previous findings that induction of hepatic ethoxyresorufin deethylase (EROD) activity takes place at daily intake levels 0.15 ng fish-derived CDD/F-TEQs/kg body weight. The study also demonstrated that hepatic vitamin A reduction takes place at somewhat higher daily exposure levels, i.e. 0.16-0.30 ng fish-derived CDD/F-TEQs/kg body weight. Halogenated fatty acids, the major component of EOC1, could not be linked to any of the measured effects. From a risk management point of view, the study provides important new information of effect levels for Ah-receptor mediated responses following low level exposure to organohalogen compounds from a matrix relevant for human exposure

July 2017 ENCALS statement on edaravone

Peer reviewe

Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS. MethodsSamples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression. ResultsThere were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 x 10(-12)), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0x10(-7)). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded C9orf72 repeats was shorter than in those without expanded C9orf72 repeats (p = 5.0x10(-4)). DiscussionAlthough telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis