Survival and re-operation rates after neurosurgical procedures in Scotland: implications for targeted surveillance of sub-clinical variant Creutzfeldt-Jakob disease.

BACKGROUND/AIM: To assess the feasibility of post-mortem surveillance for subclinical variant Creutzfeldt-Jakob disease (vCJD) at least 5 years after neurosurgical procedures. METHODS: Using Scottish record linkage, we estimated 5-year survival and re-operation rates after 4 neurosurgical procedures performed during 1993-2001 and identified as high or medium risk for transmitting vCJD: [B] drainage of extra- or subdural haematoma, [E] primary or revisional decompression operations and [H] creation of other ventricular shunts were classified as high risk; [C] operations on cerebral aneurysm (clipping) were classified as medium risk. RESULTS: Fatality rate at 1 year depended strongly on procedure, weakly or not at all on sex and era, and increased with age. Procedure rates differed by sex. The rate of subsequent neurosurgical operations was highest for procedure [H] (sole: 21%; multiple: 28%). CONCLUSION: Each year, the UK has a new cohort of some 5,000 5-year survivors after a high- or medium-risk neurosurgical procedure, whose subsequent annual mortality is at least 3%. Even if half the surviving 5-year survivors of neurosurgery since 1996 gave consent-in-life for vCJD-informative testing at post-mortem, there would be too few relevant post-mortems in 2008-2010 (around 1,600) for 'nil detections' to exclude a 1 in 1,000 subclinical vCJD rate. Autopsy surveillance beyond 2010, or among 5-year survivors of non-neurosurgical at-risk operations, would be needed.

A statistical perspective on the design of drug-court studies.

Recent meta-analyses of drug-court studies recognized the poor methodological quality of the evaluations, with only a few being randomized. This article critiques the design of the randomized studies from a statistical perspective. Learning points are identified for future drug-court studies and are applicable to evaluations both of other specialist courts and of court-based interventions more generally. The specific issues covered are randomization, describing the intervention, and baseline characteristics; study outcomes, and sample size calculations; in-program and postprogram behavior, analysis plan, and presentation of results.

Bias due to differential and non-differential disease- and exposure misclassification in studies of vaccine effectiveness.

BACKGROUND: Studies of vaccine effectiveness (VE) rely on accurate identification of vaccination and cases of vaccine-preventable disease. In practice, diagnostic tests, clinical case definitions and vaccination records often present inaccuracies, leading to biased VE estimates. Previous studies investigated the impact of non-differential disease misclassification on VE estimation. METHODS: We explored, through simulation, the impact of non-differential and differential disease- and exposure misclassification when estimating VE using cohort, case-control, test-negative case-control and case-cohort designs. The impact of misclassification on the estimated VE is demonstrated for VE studies on childhood seasonal influenza and pertussis vaccination. We additionally developed a web-application graphically presenting bias for user-selected parameters. RESULTS: Depending on the scenario, the misclassification parameters had differing impacts. Decreased exposure specificity had greatest impact for influenza VE estimation when vaccination coverage was low. Decreased exposure sensitivity had greatest impact for pertussis VE estimation for which high vaccination coverage is typically achieved. The impact of the exposure misclassification parameters was found to be more noticeable than that of the disease misclassification parameters. When misclassification is limited, all study designs perform equally. In case of substantial (differential) disease misclassification, the test-negative design performs worse. CONCLUSIONS: Misclassification can lead to significant bias in VE estimates and its impact strongly depends on the scenario. We developed a web-application for assessing the potential (joint) impact of possibly differential disease- and exposure misclassification that can be modified by users to their own study scenario. Our results and the simulation tool may be used to guide better design, conduct and interpretation of future VE studies.

Prevalence of maternal colonisation with group B streptococcus: a systematic review and meta-analysis.

BACKGROUND: The most important risk factor for early-onset (babies younger than 7 days) invasive group B streptococcal disease is rectovaginal colonisation of the mother at delivery. We aimed to assess whether differences in colonisation drive regional differences in the incidence of early-onset invasive disease. METHODS: We did a systematic review of maternal group B streptococcus colonisation studies by searching MEDLINE, Embase, Pascal Biomed, WHOLIS, and African Index Medicus databases for studies published between January, 1997, and March 31, 2015, that reported the prevalence of group B streptococcus colonisation in pregnant women. We also reviewed reference lists of selected studies and contacted experts to identify additional studies. Prospective studies in which swabs were collected from pregnant women according to US Centers for Disease Control and Prevention guidelines that used selective culture methods were included in the analyses. We calculated mean prevalence estimates (with 95% CIs) of maternal colonisation across studies, by WHO region. We assessed heterogeneity using the I(2) statistic and the Cochran Q test. FINDINGS: 221 full-text articles were assessed, of which 78 studies that included 73 791 pregnant women across 37 countries met prespecified inclusion criteria. The estimated mean prevalence of rectovaginal group B streptococcus colonisation was 17·9% (95% CI 16·2-19·7) overall and was highest in Africa (22·4, 18·1-26·7) followed by the Americas (19·7, 16·7-22·7) and Europe (19·0, 16·1-22·0). Studies from southeast Asia had the lowest estimated mean prevalence (11·1%, 95% CI 6·8-15·3). Significant heterogeneity was noted across and within regions (all p≤0·005). Differences in the timing of specimen collection in pregnancy, selective culture methods, and study sample size did not explain the heterogeneity. INTERPRETATION: The country and regional heterogeneity in maternal group B streptococcus colonisation is unlikely to completely explain geographical variation in early-onset invasive disease incidence. The contribution of sociodemographic, clinical risk factor, and population differences in natural immunity need further investigation to understand these regional differences in group B streptococcus maternal colonisation and early-onset disease. FUNDING: None.

Drugs-Related Death Soon after Hospital-Discharge among Drug Treatment Clients in Scotland: Record Linkage, Validation, and Investigation of Risk-Factors.

We validate that the 28 days after hospital-discharge are high-risk for drugs-related death (DRD) among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD), including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29-90 days, 91 days-1 year, >1 year since most recent hospital discharge versus 'never admitted'. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0-1 versus 2+ days), and main discharge-diagnosis. We confirm SDMD clients' high DRD-rate soon after hospital-discharge in 2006-2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever-injectors for 222/290. Hospital-discharge remains a period of increased DRD-vulnerability in 2006-2010, as in 1996-2006, especially for those with a history of injecting.

Meningococcal serogroup B vaccine (4CMenB): Booster dose in previously vaccinated infants and primary vaccination in toddlers and two-year-old children.

OBJECTIVE: The multicomponent, recombinant serogroup B vaccine, 4CMenB, is approved in Europe, Canada and Australia from two months of age. We investigated persistence to booster doses at 12 months of age following infant vaccination, and immune response to catch-up vaccination of toddlers and children up to two years of age. METHODS: We assessed persistence of immune responses after one year in participants vaccinated as infants, and responses to two doses at 12-15 or 24-26 months of age in vaccine-naïve children, as serum bactericidal activity with human complement (hSBA) against indicator strains for four vaccine antigens. Adverse events were recorded after each vaccination. RESULTS: High antibody titers were induced against all four 4CMenB components following booster vaccination in infant-primed toddlers and after two doses in previously unvaccinated toddlers or two-year-olds. Antibodies waned over 12 months, particularly those against NZ OMV. Systemic reactogenicity in toddlers was lower than in infants, and lower again in vaccine-naïve two-year-olds. Local reactogenicity was common in all groups. CONCLUSIONS: Four infant or two toddler 4CMenB vaccinations elicit immune responses believed to be protective for the first two years of life, which can be boosted. Reactogenicity is lower in toddlers than in infants.

A record-linkage study of drug-related death and suicide after hospital discharge among drug-treatment clients in Scotland, 1996-2006.

AIMS: To investigate the relationship between time after hospital discharge and drug-related death (DRD) and suicide among drug users in Scotland, while controlling for potential confounders. DESIGN: Cohort study. SETTING AND PARTICIPANTS: The 69 457 individuals who registered for drug treatment in Scotland during 1 April 1996-31 March 2006. MEASUREMENTS: Time-at-risk was from the date of an individual's first attendance at drug treatment services after 1 April 1996 until the earlier date of death or end-of-study, 31 March 2006, and was categorized according to time since the most recent hospitalization, as during hospitalization, within 28 days, 29-90 days, 91 days to 1 year and >1 year since discharge from most recent hospital stay versus 'never admitted' (reference). FINDINGS: Time-periods soon after discharge were associated with increased risk of DRD. DRD rates per 1000 person-years were: 87 (95% CI: 72-103) during hospitalization, 21 (18-25) within 28 days, 12 (10-15) during 29-90 days and 8.5 (7.5-9.5) during 91 days to 1 year after discharge versus 4.2 (3.7-4.7) when >1 year after most recent hospitalization and 1.9 (1.7-2.1) for those never admitted. Adjusted hazard ratios by time since hospital discharge (versus never admitted) were: 9.6 (95% CI: 8-12) within 28 days, 5.6 (4.6-6.8) during days 29-90, thereafter 4.0 (3.5-4.7) and 2.3 (2.0-2.7) when >1 year. Non-drug-related suicides were less frequent than DRDs (269 versus 1383) but a similar risk pattern was observed. CONCLUSIONS: In people receiving treatment for drug dependence, discharge from a period of hospitalization marks the start of a period of heightened vulnerability to drug-related death.

Mortality of those who attended drug services in Scotland 1996-2006: record-linkage study.

BACKGROUND: We examine major causes of death amongst persons in contact with drug-treatment services across Scotland during April 1996-March 2006, hereafter Scottish Drug Misuse Database (SDMD) cohort. METHODS: Drug-treatment records were linked to national registers of deaths and hepatitis C virus (HCV) diagnoses. For eras 1996/97-2000/01 and 2001/02-2005/06, we calculated cause-specific death-rates and standardised mortality ratios (SMRs) using age-, sex- and calendar-rates of the general Scottish population. Major causes of death were identified by high SMRs (>5 across eras) or rates (>50 per 100,000 person-years in either era), and their time-specific influences characterised by proportional hazards analyses. RESULTS: The SDMD cohort comprised 69,456 individuals, 350,315 person-years and 2590 deaths. The overall SMR reduced from 6.4 (95% CI: 6.0-6.9) to 4.8 (95% CI: 4.6-5.0) between eras. We identified five major causes of death: drug-related (1383 deaths), homicide (118) and infectious diseases (90) with high SMRs; suicide (269) and digestive system disease (168) with high rates. HCV diagnosis marked individuals with at least double the risk of cause-specific mortality, including adjusted hazard ratio (HR) for no HCV diagnosis of 0.46 (95% CI: 0.41-0.53) for drug-related deaths (DRDs) and 0.15 (95% CI: 0.10-0.22) for death from digestive system disease. Increased DRD risk at older age (>34 years) appeared specific to HCV-diagnosed individuals (interaction: χ1²=7.7, p=0.01). Alcohol misuse increased HRs: for DRD (1.76, 95% CI: 1.50-2.06), suicide (1.88, 95% CI: 1.35-2.60), deaths from digestive system disease (3.19, 95% CI: 2.21-4.60) and non-major causes (1.87, 95% CI: 1.49-2.35). Stimulant misuse increased suicide risk: adjusted HR 1.91 (95% CI: 1.43-2.54). CONCLUSIONS: Drug-users in Scotland are exposed to variously increased mortality risks. HCV-diagnosed individuals are particularly vulnerable, and may need additional support.

Exploring methods to investigate sentencing decisions.

The determinants of sentencing are of much interest in criminal justice and legal research. Understanding the determinants of sentencing decisions is important for ensuring transparent, consistent, and justifiable sentencing practice that adheres to the goals of sentencing, such as the punishment, rehabilitation, deterrence, and incapacitation of the offender, as well as reparation for the victim. It is important to frame research questions on sentencing that can feasibly be answered by appropriate research methods, within the constraints of limited time and resources. For illustration, this article presents three methodological approaches for investigating the factors that may influence sentencing decisions: multilevel analysis using existing sentencing data; sampling of, and data collection from, sentenced court case files; and experimental designs involving sentencers deciding on hypothetical cases. The strengths and weaknesses of each approach are compared and discussed.

Meta-analysis of drug-related deaths soon after release from prison.

AIMS: The transition from prison back into the community is particularly hazardous for drug-using offenders whose tolerance for heroin has been reduced by imprisonment. Studies have indicated an increased risk of drug-related death soon after release from prison, particularly in the first 2 weeks. For precise, up-to-date understanding of these risks, a meta-analysis was conducted on the risk of drug-related death in weeks 1 + 2 and 3 + 4 compared with later 2-week periods in the first 12 weeks after release from prison. METHODS: English-language studies were identified that followed up adult prisoners for mortality from time of index release for at least 12 weeks. Six studies from six prison systems met the inclusion criteria and relevant data were extracted independently. RESULTS: These studies contributed a total of 69 093 person-years and 1033 deaths in the first 12 weeks after release, of which 612 were drug-related. A three- to eightfold increased risk of drug-related death was found when comparing weeks 1 + 2 with weeks 3-12, with notable heterogeneity between countries: United Kingdom, 7.5 (95% CI: 5.7-9.9); Australia, 4.0 (95% CI: 3.4-4.8); Washington State, USA, 8.4 (95% CI: 5.0-14.2) and New Mexico State, USA, 3.1 (95% CI: 1.3-7.1). Comparing weeks 3 + 4 with weeks 5-12, the pooled relative risk was: 1.7 (95% CI: 1.3-2.2). CONCLUSIONS: These findings confirm that there is an increased risk of drug-related death during the first 2 weeks after release from prison and that the risk remains elevated up to at least the fourth week.