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Background The US Food and Drug Administration has established a policy of substantially discounting the health benefits of reduced smoking in its evaluation of proposed regulations because of the cost to smokers of the supposed lost pleasure they suffer by no longer smoking. This study used data from nine countries of the former Soviet Union (fSU) to explore this association in a setting characterised by high rates of (male) smoking and smoking-related mortality. Methods Data came from a cross-sectional populationbased study undertaken in 2010/2011 in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia and Ukraine. Information was collected from 18 000 respondents aged ≥18 on smoking status (never, ex-smoking and current smoking), cessation attempts and nicotine dependence. The association between these variables and self-reported happiness was examined using ordered probit regression analysis. Results In a pooled country analysis, never smokers and ex-smokers were both significantly happier than current smokers. Smokers with higher levels of nicotine dependence were significantly less happy than those with a low level of dependence. Conclusions This study contradicts the idea that smoking is associated with greater happiness. Moreover, of relevance for policy in the fSU countries, given the lack of public knowledge about the detrimental effects of smoking on health but widespread desire to quit reported in recent research, the finding that smoking is associated with lower levels of happiness should be incorporated in future public health efforts to help encourage smokers to quit by highlighting that smoking cessation may result in better physical and emotional health. [ABSTRACT FROM AUTHOR]

The authors discusses a study which explored the link between discrepancies and retractions in clinical trial reports. They explain that the researchers make the conclusion that discrepancies or errors could be an indication of unreliability in clinical trials. They further assert that the researchers perform a case-control study and make generalizations based on sensitivity and specificity. The authors argue that while the link may be real, its practical application is unlikely.

One of the key learning objectives in any health professional course is to develop ethical and judicious practice. Therefore, it is important to address how medical and pharmacy students respond to, and deal with, ethical dilemmas in their clinical environments. In this paper, we examined how students communicated their resolution of ethical dilemmas and the alignment between these communications and the four principles developed by Beauchamp and Childress. Three hundred and fifty-seven pharmacy and medical students (overall response rate=63%) completed a questionnaire containing four clinical case scenarios with an ethical dilemma. Data were analysed using multiple methods. The findings revealed that 73% of the qualitative responses could be exclusively coded to one of the 'four principles' determined by the Beauchamp and Childress' framework. Additionally, 14% of responses overlapped between the four principles (multiple codes) and 13% of responses could not be coded using the framework. The subsequent subgroup analysis revealed different response patterns depending on the case being reviewed. The findings showed that when students are faced with challenging ethical dilemmas their responses can be aligned with the Beauchamp and Childress framework, although more contentious dilemmas involving issues of law are less easily categorised. The differences between year and discipline groups show students are developing ethical frames of reference that may be linked with their teaching environments and their levels of understanding. Analysis of these response patterns provides insight into the way students will likely respond in 'real' settings and this information may help educators prepare students for these clinical ethical dilemmas. [ABSTRACT FROM AUTHOR]

Purpose: Functional MRI (fMRI) is becoming increasingly integrated into clinical practice for presurgical mapping. Current efforts are focused on validating data quality, with reliability being a major factor. In this paper, we demonstrate the utility of a recently developed approach that uses receiver operating characteristic-reliability (ROC-r) to: (1) identify reliable versus unreliable data sets; (2) automatically select processing options to enhance data quality; and (3) automatically select individualised thresholds for activation maps.Methods: Presurgical fMRI was conducted in 16 patients undergoing surgical treatment for brain tumours. Within-session test-retest fMRI was conducted, and ROC-reliability of the patient group was compared to a previous healthy control cohort. Individually optimised preprocessing pipelines were determined to improve reliability. Spatial correspondence was assessed by comparing the fMRI results to intraoperative cortical stimulation mapping, in terms of the distance to the nearest active fMRI voxel.Results: The average ROC-r reliability for the patients was 0.58±0.03, as compared to 0.72±0.02 in healthy controls. For the patient group, this increased significantly to 0.65±0.02 by adopting optimised preprocessing pipelines. Co-localisation of the fMRI maps with cortical stimulation was significantly better for more reliable versus less reliable data sets (8.3±0.9 vs 29±3 mm, respectively).Conclusions: We demonstrated ROC-r analysis for identifying reliable fMRI data sets, choosing optimal postprocessing pipelines, and selecting patient-specific thresholds. Data sets with higher reliability also showed closer spatial correspondence to cortical stimulation. ROC-r can thus identify poor fMRI data at time of scanning, allowing for repeat scans when necessary. ROC-r analysis provides optimised and automated fMRI processing for improved presurgical mapping. [ABSTRACT FROM AUTHOR]

Objective: Neurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case-control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.Methods: Guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and 'grey' literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis.Results: CSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001).Conclusions: CSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease 'activity' rather than as a marker of disability or disease stage. [ABSTRACT FROM AUTHOR]

Background and aims Bicycling may be less appealing in parts of the world where cycling is less safe. Differences between jurisdictions suggest route design is key to improving safety and increasing ridership. Previous studies faced difficulties in effectively assessing denominators for risk calculations and controlling confounding. This paper describes the advantages of the case-crossover design of the Bicyclists' Injuries and the Cycling Environment study to address these challenges to observational studies of cycling safety. Methods Injured cyclists were recruited from the emergency departments of five hospitals in Vancouver and Toronto, Canada. In 18 months, 690 participants were successfully recruited and interviewed. Each participant was interviewed to map the route of their injury trip, identify the injury site and select two control sites at random from the same route. Infrastructural characteristics at each study site were scored by site observers who were blinded as to whether sites were crash or comparison sites. Analyses will compare infrastructural variables between case and control sites with conditional logistic regression. Discussion This study presents a novel application of the case-crossover design to the evaluation of relationships between infrastructure and cycling safety while controlling confounders and exposure to risk. It is hoped that the value of this method and the efficiency of the recruitment process will encourage replication in other locations, to expand the range of cycling infrastructure compared and to facilitate evidence-based cycling infrastructure choices that can make cycling safer and more appealing. [ABSTRACT FROM AUTHOR]

In this paper some methodological problems particularly relevant to case-control studies of injury are illustrated by reference to previous childhood injury case-control studies. In contrast to studies of disease, where 'person time' constitutes the observational experience of interest, in injury studies person time engaged in a particular activity is often more appropriate. The implications for the definition of the study base are discussed. The potential for hospital admission bias in injury case-control studies is considered along with potential strategies for avoiding it. The importance of errors in exposure measurement, including those arising from inappropriate induction time assumptions, are illustrated. Finally, the potential for bias resulting from the combination of etiologically unrelated injury outcomes into a single outcome measure is illustrated and discussed. [ABSTRACT FROM AUTHOR]

Background Despite all the gains that have been achieved with endovascular mechanical thrombectomy revascularization and intravenous thrombolysis logistics since 2015, there is still a subgroup of patients with salvageable brain tissue for whom persistent emergent large vessel occlusion portends a catastrophic outcome. Objective To test the safety and efficacy of emergent microsurgical intervention in patients with acute ischemic stroke and symptomatic middle cerebral artery occlusion after failure of mechanical thrombectomy. Methods A prospective two-center cohort study was conducted. Patients with acute ischemic stroke and middle cerebral artery occlusion for whom recanalization failed at center 1 were randomly allocated to the microsurgical intervention group (MSIG) or control group 1 (CG1). All similar patients at center 2 were included in the control group 2 (CG2) with no surgical intervention. Microsurgical embolectomy and/or extracranial-intracranial bypass was performed in all MSIG patients at center 1. Results A total of 47 patients were enrolled in the study: 22 at center 1 (12 allocated to the MSIG and 10 to the CG1) and 25 patients at center 2 (CG2). MSIG group patients showed a better clinical outcome on day 90 after the stroke, where a modified Rankin Scale score of 0-2 was reached in 7 (58.3%) of 12 patients compared with 1/10 (10.0%) patients in the CG1 and 3/12 (12.0%) in the CG2. Conclusions This study demonstrated the potential for existing microsurgical techniques to provide good outcomes in 58% of microsurgically treated patients as a third-tier option. [ABSTRACT FROM AUTHOR]

Objective: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated.Methods: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH.Results: A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones.Conclusions: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions. [ABSTRACT FROM AUTHOR]

Background: Musculoskeletal symptoms limit adherence to exercise interventions for individuals with type 2 diabetes. People with diabetes may be susceptible to tendinopathy due to chronically elevated blood glucose levels. Therefore, we aimed to investigate this potential association by systematically reviewing and meta-analysing case-control, cross-sectional, and studies that considered both of these conditions.Methods: Nine medical databases and hand searching methods were used without year limits to identify all relevant English language articles that considered diabetes and tendinopathy. Two authors applied exclusion criteria and one author extracted data with verification by a second author. Meta-analysis was conducted using a random effects model. Results were expressed as odds ratio (OR), mean difference or standardised mean difference with a confidence intervals (95% CI). Heterogeneity was assessed by I(2).Findings: 31 studies were included in the final analysis of which 26 recruited people with diabetes and five recruited people with tendinopathy. Tendinopathy was more prevalent in people with diabetes (17 studies, OR 3·67, 95% CI 2·71 to 4·97), diabetes was more prevalent in people with tendinopathy (5 studies, OR 1·28, 95% CI 1·10 to 1·49), people with diabetes and tendinopathy had a longer duration of diabetes than people with diabetes only (6 studies, mean difference 5·26 years, 95% CI 4·15 to 6·36) and people with diabetes had thicker tendons than controls (9 studies, standardised mean difference 0·79 95% CI 0·47 to 1·12).Interpretation: These findings provide strong evidence that diabetes is associated with higher risk of tendinopathy. This is clinically relevant as tendinopathy may affect adherence to exercise interventions for diabetes. [ABSTRACT FROM AUTHOR]

Objectives: To compare the frequency of discrepancies in retracted reports of clinical trials with those in adjacent unretracted reports in the same journal.Design: Blinded case-control study.Setting: Journals in PubMed.Population: 50 manuscripts, classified on PubMed as retracted clinical trials, paired with 50 adjacent unretracted manuscripts from the same journals. Reports were randomly selected from PubMed in December 2012, with no restriction on publication date. Controls were the preceding unretracted clinical trial published in the same journal. All traces of retraction were removed. Three scientists, blinded to the retraction status of individual reports, reviewed all 100 trial reports for discrepancies. Discrepancies were pooled and cross checked before being counted into prespecified categories. Only then was the retraction status unblinded for analysis.Main Outcome Measure: Total number of discrepancies (defined as mathematically or logically contradictory statements) in each clinical trial report.Results: Of 479 discrepancies found in the 100 trial reports, 348 were in the 50 retracted reports and 131 in the 50 unretracted reports. On average, individual retracted reports had a greater number of discrepancies than unretracted reports (median 4 (interquartile range 2-8.75) v 0 (0-5); P<0.001). Papers with a discrepancy were significantly more likely to be retracted than those without a discrepancy (odds ratio 5.7 (95% confidence interval 2.2 to 14.5); P<0.001). In particular, three types of discrepancy arose significantly more frequently in retracted than unretracted reports: factual discrepancies (P=0.002), arithmetical errors (P=0.01), and missed P values (P=0.02). Results from a retrospective analysis indicated that citations and journal impact factor were unlikely to affect the result.Conclusions: Discrepancies in published trial reports should no longer be assumed to be unimportant. Scientists, blinded to retraction status and with no specialist skill in the field, identify significantly more discrepancies in retracted than unretracted reports of clinical trials. Discrepancies could be an early and accessible signal of unreliability in clinical trial reports. [ABSTRACT FROM AUTHOR]

Background: Both vaccination and physical activity have been shown to independently decrease the likelihood of severe COVID-19 infection.Objective: To assess the association between regular physical activity and vaccination against COVID-19 among healthcare workers.Methods: A test negative case-control study design was used to estimate the risk of having an associated COVID-19-related hospital admission, among individuals who were unvaccinated compared with those who were fully vaccinated with Ad26.COV2.S (>28 days after a single dose). 196 444 participant tests were stratified into three measured physical activity subgroups with low, moderate and high activity, to test the hypothesis that physical activity is an effect modifier on the relationship between vaccination and hospitalisation.Results: Vaccine effectiveness against a COVID-19-related admission among vaccinated individuals within the low activity group was 60.0% (95% CI 39.0 to 73.8), 72.1% (95% CI 55.2 to 82.6) for the moderate activity group, and 85.8% (95% CI 74.1 to 92.2) for the high activity group. Compared with individuals with low activity levels, vaccinated individuals with moderate and high activity levels had a 1.4 (95% CI 1.36 to 1.51) and 2.8 (95% CI 2.35 to 3.35) times lower risk of COVID-19 admission, respectively (p value <0.001 for both groups).Conclusions: Regular physical activity was associated with improved vaccine effectiveness against COVID-19 hospitalisation, with higher levels of physical activity associated with greater vaccine effectiveness. Physical activity enhances vaccine effectiveness against severe COVID-19 outcomes and should be encouraged by greater public health messaging. [ABSTRACT FROM AUTHOR]

Background Childhood falls are an important global public health problem, but there is lack of evidence about their prevention. Falls on one level result in considerable morbidity and they are costly to health services. Objective To estimate ORs for falls on one level in children aged 0-4 years for a range of safety behaviours, safety equipment use and home hazards. Design, setting and participants Multicentre case-control study at hospitals, minor injury units and general practices in and around four UK study centres. Participants included 582 children less than 5 years of age with a medically attended fall injury occurring at home and 2460 controls matched on age, sex, calendar time and study centre. Main outcome measure Fall on one level. Results Cases' most common injuries were bangs on the head (52%), cuts or grazes not needing stitches (29%) or cuts or grazes needing stitches (17%). Comparing cases to community controls in the adjusted analyses, significant findings were observed for only two exposures. Injured children were significantly less likely to live in a household without furniture corner covers (adjusted OR (AOR) 0.72, 95% CI 0.55 to 0.95), or without rugs and carpets firmly fixed to the floor (AOR 0.76, 95% CI 0.59 to 0.98). Conclusions We did not find any safety practices, use of safety equipment or home hazards associated with a reduced risk of fall on one level. Our findings do not provide evidence to support changes to current injury prevention practice. [ABSTRACT FROM AUTHOR]

Background Plain packaging (PP) for tobacco products was fully implemented in Australia on 1 December 2012 along with larger graphic health warnings. Using longitudinal data from the Australian arm of the ITC Four Country Survey, we examined attitudes to the new packs before and after implementation, predictors of attitudinal change, and the relationship between support and quitting activity. Methods A population-based cohort study design, with some cross-sectional analyses. Surveys of Australian smokers assessed attitudes to PP at four time points prior to implementation (from 2007 to 2012) and one post-implementation wave collected (early/mid-2013). Results Trend analysis showed a slight rise in opposition to PP among smokers in the waves leading up to their implementation, but no change in support. Support for PP increased significantly after implementation (28.2% pre vs 49% post), such that post-PP more smokers were supportive than opposed (49% vs 34.7%). Multivariate analysis showed support either before or after implementation was predicted by belief in greater adverse health impacts of smoking, desire to quit and lower addiction. Among those not supportive before implementation, having no clear opinion about PP (versus being opposed) prior to the changes also predicted support post-implementation. Support for PP was prospectively associated with higher levels of quitting activity. Conclusions Since implementation of PP along with larger warnings, support among Australian smokers has increased. Support is related to lower addiction, stronger beliefs in the negative health impacts of smoking, and higher levels of quitting activity. [ABSTRACT FROM AUTHOR]

The article presents a summary of a research paper on the association between cardiovascular events and sodium-containing effervescent, dispersible and soluble drugs that was published on bmj.com. The study, which involved residents in Great Britain, showed that sodium-containing formulations of commonly prescribed drugs are associated with increased risk of cardiovascular events in patients. It adds that the increased risk was primarily driven by an increased risk of hypertension and stroke.

Objective: To assess the relationship between influenza vaccination and risk of a first acute myocardial infarction (AMI) in the general population by different epidemic periods.Methods: This is a population-based case-control study carried out in BIFAP (Base de datos para la investigación farmacoepidemiológica en atención primaria), over 2001-2015, in patients aged 40-99 years. Per each incident AMI case, five controls were randomly selected, individually matched for exact age, sex and index date (AMI diagnosis). A patient was considered vaccinated when he/she had a recorded influenza vaccination at least 14 days before the index date within the same season. The association between influenza vaccination and AMI risk was assessed through a conditional logistic regression, computing adjusted ORs (AOR) and their respective 95% CIs. The analysis was performed overall and by each of the three time epidemic periods per study year (pre-epidemic, epidemic and postepidemic).Results: We identified 24 155 AMI cases and 120 775 matched controls. Of them, 31.4% and 31.2%, respectively, were vaccinated, yielding an AOR of 0.85 (95% CI 0.82 to 0.88). No effect modification by sex, age and background cardiovascular risk was observed. The reduced risk of AMI was observed shortly after vaccination and persisted over time. Similar results were obtained during the pre-epidemic (AOR=0.87; 95% CI 0.79 to 0.95), epidemic (AOR=0.89; 95% CI 0.82 to 0.96) and postepidemic (AOR=0.83; 95% CI 0.79 to 0.87) periods. No association was found with pneumococcal vaccine (AOR=1.10; 95% CI 1.06 to 1.15).Conclusions: Results are compatible with a moderate protective effect of influenza vaccine on AMI in the general population, mostly in primary prevention, although bias due to unmeasured confounders may partly account for the results. [ABSTRACT FROM AUTHOR]

Objective: Children with tracheomalacia can develop chronic lower airway infection and neutrophilic inflammation. It is plausible children with tracheomalacia are at increased risk of developing bronchiectasis. We hypothesised that compared with controls, tracheomalacia in children is associated with bronchiectasis.Design: Single-centre, case-control study.Setting and Patients: 45 children with chest high-resolution CT (c-HRCT) confirmed bronchiectasis (cases) and enrolled in the Australian Bronchiectasis Registry were selected randomly from Queensland, and 90 unmatched children without chronic respiratory symptoms or radiographic evidence of bronchiectasis (disease controls). Cases and controls had flexible bronchoscopy performed for clinical reasons within 4 weeks of their c-HRCT.Interventions: The bronchoscopy videos were reviewed in a blinded manner for: (a) any tracheomalacia (any shape deformity of the trachea at end-expiration) and (b) tracheomalacia defined by the European Respiratory Society (ERS) statement (>50% expiratory reduction in the cross-sectional luminal area).Main Outcome Measures and Results: Cases were younger (median age=2.6 years, IQR 1.5-4.1) than controls (7.8 years, IQR 3.4-12.8), but well-balanced for sex (56% and 52% male, respectively). Using multivariable analysis (adjusted for age), the presence of any tracheomalacia was significantly associated with bronchiectasis (adjusted OR (ORadj)=13.2, 95% CI 3.2 to 55), while that for ERS-defined tracheomalacia further increased this risk (ORadj=24.4, 95% CI 3.4 to infinity).Conclusion: Bronchoscopic-defined tracheomalacia is associated with childhood bronchiectasis. While causality cannot be inferred, children with tracheomalacia should be monitored for chronic (>4 weeks) wet cough, the most common symptom of bronchiectasis, which if present should be treated and then investigated if the cough persists or is recurrent. [ABSTRACT FROM AUTHOR]

Objectives To investigate the effect of secondhand smoke exposure from a partner on the risk of having a newborn baby with neural tube defects (NTDs) in Chinese non-smoking women. Methods Data were derived from an on-going population-based case-control study of external malformations in northern China. The case group included 580 infants or fetuses with NTDs identified between November 2002 and December 2007. Controls were 795 newborn infants without major external malformations. Data were collected by trained health workers through face-to-face interviews within 1 week after delivery. Results A total of 81.4% of partners of case women and 71.8% of partners of control women smoked during the women's peri-conceptional period. The adjusted OR for NTDs associated with partner smoking was 1.6 (95% CI 1.2 to 2.1). Compared with non-smoking women with non-smoking partners, fetal NTD risk among women with smoking partners was 1.7 (1.3 to 2.4) and 1.1 (0.7 to 1.7) for women exposed and not exposed to partner smoking, respectively. Among women who were exposed to partner smoking, the risk of NTDs was 1.4 (0.9 to 2.0), 1.8 (1.2 to 2.6), 1.9 (1.2 to 3.0) and 2.7 (1.6 to 4.7) for partner smoking of <1, 1-9, 10-19 and ≥20/day, respectively (p for trend <0.001). Conclusion Peri-conceptional exposure to partner smoking may increase the risk of NTDs in the offspring of Chinese non-smoking women. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: The purpose of this study was to identify the risk factors predisposing to aneurysm rupture and to provide a reliable estimation for likelihood of rupture in unruptured intracranial aneurysms. METHODS: The authors performed a nested case-control study of 290 aneurysms (123 unruptured aneurysms and 167 ruptured aneurysms) occurring during a prospective cohort study in 1493 consecutive patients with newly diagnosed intracranial aneurysm and were treated in a single institute between January 1995 and December 2006. Controls were matched for age, treatment group, number of lesion, sex, region and study period in which the incidence of ruptured and unruptured intracranial aneurysm was equivalently balanced. The authors assessed the predictive risk factors associated with aneurysmal rupture based on the clinical and angiographic findings reported in the patients' medical records. RESULTS: Between January 1997 and December 2002, 167 patients with ruptured intracranial aneurysms were assigned to group 1, and 123 patients with unruptured intracranial aneurysms during the same period were assigned to group 2. Aspect ratio (OR 3.76), maximum diameter of neck (Nmax) ≤3 mm (OR 2.56) and family history of cerebrovascular disease (OR 5.63) were strongly correlated with aneurysm rupture (p<0.05). CONCLUSIONS: There are differences between the clinical and intrinsic characteristics of patients with unruptured and ruptured intracranial aneurysm. It will be helpful to make rational decisions regarding the optimal therapeutic strategy for unruptured intracranial aneurysm. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the occupants in vehicles with better safety ratings according to EuroNCAP sustain fewer fatal and severe injuries than occupants in vehicles with worse experimental safety ratings when in frontal crashes. Design: Caseecontrol study. Setting: A representative sample of crashes in Britain from 1996 to 2008 as gathered in the Cooperative Crash Injury Study (CCIS) database under the auspices of the UK Department of Transportation and augmented with EuroNCAP experimental ratings for each crashed vehicle. Subjects: Drivers and front seat passengers while occupants of vehicles for which EuroNCAP test results were available and who met inclusion criteria meant to select those in crashes similar to those in the frontal experimental setting. Main outcome measures: Fatality and severe MAIS3+ injuries to the head, thorax, pelvis and lower extremities. Results: The multivariate Poisson regression models on the 1259 cases who sustained crash conditions most similar to the experimental ones showed no statistically significant effect on either mortality or MAIS3+ injury in real-world crashes when travelling in cars with better safety ratings. For example, when compared to a driver in a vehicle rated as safest for head injuries MAIS3+ in frontal crashes, drivers in vehicles rated yellow or orange presented adjusted ORs of 0.6 (0.2 to 1.7) and 0.8 (0.3 to 2.1), respectively. Conclusions: No statistically significant relationships between the EuroNCAP safety scores and real-world death or severe injury outcomes were found, suggesting the need to review biomechanical criteria chosen to set cut-off points for the rating system. [ABSTRACT FROM AUTHOR]

Objectives: Mycoplasma genitalium has been associated with cervicitis, endometritis, and tubal factor infertility. Because the ability of this bacterium to ascend and infect the fallopian tube remains undefined, we performed an investigation to determine the prevalence of M genitalium in fallopian tube, endometrial, and cervical specimens from women laparoscopically diagnosed with acute salpingitis in Nairobi, Kenya.Methods: Women presenting with pelvic inflammatory disease were laparoscopically diagnosed with salpingitis. Infection with M genitalium in genital specimens was determined by polymerase chain reaction (PCR).Results: Of 123 subjects with acute salpingitis, M genitalium was detected by PCR in the cervix and/or endometrium in nine (7%) participants, and in a single fallopian tube specimen. In addition, those infected with M genitalium were more often HIV infected than women not infected by M genitalium (seven of nine (78%) v 42 of 114 (37%), p<0.03).Conclusions: M genitalium is able to ascend into the fallopian tube, but its association with tubal pathology requires further investigation. [ABSTRACT FROM AUTHOR]

Objective: To examine the quantitative relation between exposure to isocyanates and occupational asthma, and to explore the role of atopy and smoking in occurrence of the disease.Method: A case-referent study was undertaken of cases from two manufacturing companies (A and B) from which referents without disease could be selected and reliable exposure measurements were available. In company A, 27 cases mainly attributed to toluene diisocyanate (TDI) were matched to 51 referents on work area, start and duration of employment, sex, and age. Exposures were estimated from existing measurements by job category. In company B there were seven cases attributed to 4,4'-diphenylmethane diisocyanate (MDI) in two areas of the plant; 12 non-cases from the same areas were used as referents. Personal exposure measurements were available for all cases and 11 referents.Results: No difference in peak exposures between cases and referents was found in either plant; but in both, time weighted average (TWA) exposures at the time of onset of asthma were higher for cases. In A, the mean TWA exposure for cases was 1.5 (95% confidence interval (95% CI) 1.2 to 1.8) ppb compared with 1.2 (1.0 to 1.4) ppb for referents. From a matched analysis, the odds ratio (OR) associated with 8 hour TWA exposure to isocyanates greater than 1.125 ppb (the median concentration for the referent group) was 3.2 (95% CI 0.96 to 10.6; p=0.06). Occupational asthma was associated with a pre-employment history of atopic illness (OR 3. 5, p=0.04) and, less strongly, with smoking (OR 2.1, p=0.14). In B, small numbers limited analysis, but three of seven cases had at least one TWA exposure measurement greater than 5 ppb compared with one of 11 referents (OR 7.5, p=0.09).Conclusion: Asthma can occur at low concentrations of isocyanates, but even at low concentrations, the higher the exposure the greater the risk. By contrast with other studies, smoking and atopy seemed to increase the odds of occupational asthma due to isocyanates, but did not affect the estimate of risk associated with exposure. [ABSTRACT FROM AUTHOR]

Objective: Patients with bipolar disorder and schizophrenia are at high cardiovascular risk; yet, the risk of out-of-hospital cardiac arrest (OHCA) compared with the general population remains scarcely investigated.Methods: We conducted a nested case-control study using Cox regression to assess the association of bipolar disorder and schizophrenia with the HRs of OHCA of presumed cardiac cause (2001-2015). Reported are the HRs with 95% CIs overall and in subgroups defined by established cardiac disease, cardiovascular risk factors and psychotropic drugs.Results: We included 35 017 OHCA cases and 175 085 age-matched and sex-matched controls (median age 72 years and 66.9% male). Patients with bipolar disorder or schizophrenia had overall higher rates of OHCA compared with the general population: HR 2.74 (95% CI 2.41 to 3.13) and 4.49 (95% CI 4.00 to 5.10), respectively. The association persisted in patients with both cardiac disease and cardiovascular risk factors at baseline (bipolar disorder HR 2.14 (95% CI 1.72 to 2.66), schizophrenia 2.84 (95% CI 2.20 to 3.67)) and among patients without known risk factors (bipolar disorder HR 2.14 (95% CI 1.09 to 4.21), schizophrenia HR 5.16 (95% CI 3.17 to 8.39)). The results were confirmed in subanalyses only including OHCAs presenting with shockable rhythm or receiving an autopsy. Antipsychotics-but not antidepressants, lithium or antiepileptics (the last two only tested in bipolar disorder)-increased OHCA hazard compared with no use in both disorders.Conclusions: Patients with bipolar disorder or schizophrenia have a higher rate of OHCA compared with the general population. Cardiac disease, cardiovascular risk factors and antipsychotics represent important underlying mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: A population based case-control study was conducted in a highly agricultural area in the north east of Italy to evaluate the association between farming and animal breeding and the risk of developing non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL).Methods: Occupational histories and other data were collected by personal interview on 164 NHLs, 23 CLLs, diagnosed in 1988-90, and on 977 controls. This paper only reports the results of the analysis relative to the coding of job titles through the modified International Labour Office (ILO) classification. Estimates of odds ratios (ORs) for occupational variables were calculated, after adjustment for sex, age, altitude of municipality, first degree familiarity, and previous Herpes zoster infection.Results: From the analysis of the most frequent occupational categories, no occupation showed a significantly high risk. When the two job titles farmers only and farmer-breeders who are also involved in animal breeding are classified within the extremely varied occupation of agriculture or animal-breeding or fishing, a high risk for NHLs and CLLs is seen in the farmer-breeders (OR 1.79, 95% CI 1.22 - 2.63). Analyses according to histological type show that the risks are concentrated in CLLs and in low grade NHLs. No effect or trend by period at work or duration of employment in farming and animal breeding was found.Conclusion: Subjects working in agriculture associated with animal breeding are at high risk of NHL/CLLs, particularly CLLs and low grade NHLs. This finding could be related to the use of chemicals in agriculture or to exposure to animal transmitted diseases or specific chemicals used in animal breeding. [ABSTRACT FROM AUTHOR]

Objectives: We sought to identify metabolic changes potentially related to rheumatoid arthritis (RA) pathogenesis occurring in the blood prior to its diagnosis.Methods: In a US military biorepository, serum samples collected at two timepoints prior to a diagnosis of RA were identified. These were matched to controls who did not develop RA by subject age, race and time between sample collections and RA diagnosis time to stored serum samples. Relative abundances of 380 metabolites were measured using liquid chromatography-tandem mass spectrometry. We determined whether pre-RA case versus control status predicted metabolite concentration differences and differences over time (trajectories) using linear mixed models, assessing for interactions between time, pre-RA status and metabolite concentrations. We separately examined pre-RA and pre-seropositive RA cases versus matched controls and adjusted for smoking. Multiple comparison adjustment set the false discovery rate to 0.05.Results: 291 pre-RA cases (80.8% pre seropositive RA) were matched to 292 controls, all with two serum samples (2.7±1.6 years; 1.0±0.9 years before RA/matched date). 52.0% were women; 52.8% were White, 26.8% Black and 20.4% other race. Mean age was 31.2 (±8.1) years at earliest blood draw. Fourteen metabolites had statistically significant trajectory differences among pre-RA subjects versus controls, including sex steroids, amino acid/lipid metabolism and xenobiotics. Results were similar when limited to pre seropositive RA and after adjusting for smoking.Conclusions: In this military case-control study, metabolite concentration trajectory differences in pre-RA cases versus controls implicated steroidogenesis, lipid/amino acid metabolism and xenobiotics in RA pathogenesis. Metabolites may have potential as biomarkers and/or therapeutic targets preceding RA diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of low-dose or no aspirin with conventional high-dose aspirin for the initial treatment in the acute-phase of Kawasaki disease (KD).Design: A meta-analysis and systematic review of randomised control trials and cohort studies.Methods: All available articles that compared different dosage of aspirin in the acute-phase of KD published until 20 September 2019 were included from the databases of PubMed, Embase and Cochrane Central Register of Controlled Trials Central without language restrictions. Extracted data from eligible studies were reviewed by two authors independently and analysed by using RStudio software.Results: Nine cohorts with a total of 12 182 children were enrolled. We found that low-dose (3-5 mg/kg/day) or no aspirin in the acute-phase KD was associated with reducing the risk of coronary artery lesions (CALs, OR=0.81, 95% CI 0.69 to 0.95). No differences were observed in intravenous immunoglobulin resistance, length of hospital stay and fever days after admission (OR=1.35, 95% CI 0.91 to 1.98; standard mean difference (SMD)=0.17, 95% CI -1.07 to 1.4; SMD=0.3, 95% CI -1.51 to 2.11) in the low-dose/no aspirin subgroup compared with the high-dose (≥30 mg/kg/day) aspirin subgroup. We did not identify any potential factors affecting the homogeneity of CAL risk as well as clinical important effects in all included studies.Conclusions: Prescribing low-dose or no aspirin in the acute-phase of KD might be associated with a decreased incidence of CAL. However, additional well-designed prospective trials are required to support the theory. [ABSTRACT FROM AUTHOR]

Background Intrahospital transfers have become more common as hospital staff balance patient needs with bed availability. However, this may leave patients more vulnerable to potential pathogen transmission routes via increased exposure to contaminated surfaces and contacts with individuals. Objective This study aimed to quantify the association between the number of intrahospital transfers undergone during a hospital spell and the development of a hospital- acquired infection (HAI). Methods A retrospective case-control study was conducted using data extracted from electronic health records and microbiology cultures of non- elective, medical admissions to a large urban hospital network which consists of three hospital sites between 2015 and 2018 (n=24 240). As elderly patients comprise a large proportion of hospital users and are a high- risk population for HAIs, the analysis focused on those aged 65 years or over. Logistic regression was conducted to obtain the OR for developing an HAI as a function of intrahospital transfers until onset of HAI for cases, or hospital discharge for controls, while controlling for age, gender, time at risk, Elixhauser comorbidities, hospital site of admission, specialty of the dominant healthcare professional providing care, intensive care admission, total number of procedures and discharge destination. Results Of the 24 240 spells, 2877 cases were included in the analysis. 72.2% of spells contained at least one intrahospital transfer. On multivariable analysis, each additional intrahospital transfer increased the odds of acquiring an HAI by 9% (OR=1.09; 95% CI 1.05 to 1.13). Conclusion Intrahospital transfers are associated with increased odds of developing an HAI. Strategies for minimising intrahospital transfers should be considered, and further research is needed to identify unnecessary transfers. Their reduction may diminish spread of contagious pathogens in the hospital environment. [ABSTRACT FROM AUTHOR]

Objectives: To determine if the polymorphism encoding the Arg206Cys substitution in DNASE1L3 explains the association of the DNASE1L3/PXK gene locus with systemic lupus erythematosus (SLE) and to examine the effect of the Arg206Cys sequence change on DNASE1L3 protein function.Methods: Conditional analysis for rs35677470 was performed on cases and controls with European ancestry from the SLE Immunochip study, and genotype and haplotype frequencies were compared. DNASE1L3 protein levels were measured in cells and supernatants of HEK293 cells and monocyte-derived dendritic cells expressing recombinant and endogenous 206Arg and 206Cys protein variants.Results: Conditional analysis on rs35677470 eliminated the SLE risk association signal for lead single-nucleotide polymorphisms (SNPs) rs180977001 and rs73081554, which are found to tag the same risk haplotype as rs35677470. The modest effect sizes of the SLE risk genotypes (heterozygous risk OR=1.14 and homozygous risk allele OR=1.68) suggest some DNASE1L3 endonuclease enzyme function is retained. An SLE protective signal in PXK (lead SNP rs11130643) remained following conditioning on rs35677470. The DNASE1L3 206Cys risk variant maintained enzymatic activity, but secretion of the artificial and endogenous DNASE1L3 206Cys protein was substantially reduced.Conclusions: SLE risk association in the DNASE1L3 locus is dependent on the missense SNP rs35677470, which confers a reduction in DNASE1L3 protein secretion but does not eliminate its DNase enzyme function. [ABSTRACT FROM AUTHOR]

Objective: Patients with Kawasaki disease (KD) with coronary artery enlargement at diagnosis are at the highest risk for persistent coronary artery aneurysms (CAAs) and may benefit from primary adjunctive anti-inflammatory therapy beyond intravenous immunoglobulin (IVIG). We evaluate the effect of primary adjunctive corticosteroid therapy on outcomes in patients with CAA at diagnosis.Design: Single-centre, retrospective review.Patients: Patients with KD diagnosed within 10 days of fever onset and with baseline CA z-score ≥2.5.Interventions: Primary treatment with IVIG (n=162) versus IVIG plus corticosteroids (n=48).Main Outcome Measures: Treatment resistance (persistent fever >36 hours after initial treatment), CAA regression rate.Results: Of the 92 patients with KD who received corticosteroids at our institution from 2012 to 2019, 48 met the inclusion criteria for primary adjunctive therapy. The corticosteroid group was younger and had larger baseline CAAs compared with historical controls. Demographics and laboratory values were otherwise similar between groups. The corticosteroid group had a less treatment resistance (4% vs 30%, p=0.003) and a greater improvement in C reactive protein. After adjusting for baseline CA z-score, age and baseline bilateral versus unilateral CAA, the corticosteroid group had a higher odds of (OR 2.77 (1.04, 7.42), p=0.042) and a shorter time to CAA regression (HR 1.94 (1.27, 2.96), p=0.002).Conclusion: Primary adjunctive corticosteroid therapy is associated with decreased initial treatment resistance, greater improvement in inflammatory markers and higher likelihood of CAA regression in patients who have CAA at diagnosis. Multi-centre, randomised controlled trials are needed to confirm the benefits of corticosteroids in patients with CAA at diagnosis and to compare corticosteroids with other adjunctive therapies. [ABSTRACT FROM AUTHOR]

Objective: To determine rates of psychiatric comorbidity in a clinical sample of childhood movement disorders (MDs).Design: Cohort study.Setting: Tertiary children's hospital MD clinics in Sydney, Australia and London, UK.Patients: Cases were children with tic MDs (n=158) and non-tic MDs (n=102), including 66 children with dystonia. Comparison was made with emergency department controls (n=100), neurology controls with peripheral neuropathy or epilepsy (n=37), and community controls (n=10 438).Interventions: On-line development and well-being assessment which was additionally clinically rated by experienced child psychiatrists.Main Outcome Measures: Diagnostic schedule and manual of mental disorders-5 criteria for psychiatric diagnoses.Results: Psychiatric comorbidity in the non-tic MD cohort (39.2%) was comparable to the tic cohort (41.8%) (not significant). Psychiatric comorbidity in the non-tic MD cohort was greater than the emergency control group (18%, p<0.0001) and the community cohort (9.5%, p<0.00001), but not the neurology controls (29.7%, p=0.31). Almost half of the patients within the tic cohort with psychiatric comorbidity were receiving medical psychiatric treatment (45.5%) or psychology interventions (43.9%), compared with only 22.5% and 15.0%, respectively, of the non-tic MD cohort with psychiatric comorbidity.Conclusions: Psychiatric comorbidity is common in non-tic MDs such as dystonia. These psychiatric comorbidities appear to be under-recognised and undertreated. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic pulmonary fibrosis (IPF) is a lung disease of unknown cause characterised by progressive scarring, with limited effective treatment and a median survival of only 2-3 years. Our aim was to identify potential occupational and environmental exposures associated with IPF in Australia.Methods: Cases were recruited by the Australian IPF registry. Population-based controls were recruited by random digit dialling, frequency matched on age, sex and state. Participants completed a questionnaire on demographics, smoking, family history, environmental and occupational exposures. Occupational exposure assessment was undertaken with the Finnish Job Exposure Matrix and Australian asbestos JEM. Multivariable logistic regression was used to describe associations with IPF as ORs and 95% CIs, adjusted for age, sex, state and smoking.Results: We recruited 503 cases (mean±SD age 71±9 years, 69% male) and 902 controls (71±8 years, 69% male). Ever smoking tobacco was associated with increased risk of IPF: OR 2.20 (95% CI 1.74 to 2.79), but ever using marijuana with reduced risk after adjusting for tobacco: 0.51 (0.33 to 0.78). A family history of pulmonary fibrosis was associated with 12.6-fold (6.52 to 24.2) increased risk of IPF. Occupational exposures to secondhand smoke (OR 2.1; 1.2 to 3.7), respirable dust (OR 1.38; 1.04 to 1.82) and asbestos (OR 1.57; 1.15 to 2.15) were independently associated with increased risk of IPF. However occupational exposures to other specific organic, mineral or metal dusts were not associated with IPF.Conclusion: The burden of IPF could be reduced by intensified tobacco control, occupational dust control measures and elimination of asbestos at work. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic and prognostic value of serum neurofilament light (NfL) and serum phospho-Tau181 (p-Tau181) in a large cohort of patients with frontotemporal lobar degeneration (FTLD).Methods: In this retrospective study, performed on 417 participants, we analysed serum NfL and p-Tau181 concentrations with an ultrasensitive single molecule array (Simoa) approach. We assessed the diagnostic values of serum biomarkers in the differential diagnosis between FTLD, Alzheimer's disease (AD) and healthy ageing; their role as markers of disease severity assessing the correlation with clinical variables, cross-sectional brain imaging and neurophysiological data; their role as prognostic markers, considering their ability to predict survival probability in FTLD.Results: We observed significantly higher levels of serum NfL in patients with FTLD syndromes, compared with healthy controls, and lower levels of p-Tau181 compared with patients with AD. Serum NfL concentrations showed a high accuracy in discriminating between FTLD and healthy controls (area under the curve (AUC): 0.86, p<0.001), while serum p-Tau181 showed high accuracy in differentiating FTLD from patients with AD (AUC: 0.93, p<0.001). In FTLD, serum NfL levels correlated with measures of cognitive function, disease severity and behavioural disturbances and were associated with frontotemporal atrophy and indirect measures of GABAergic deficit. Moreover, serum NfL concentrations were identified as the best predictors of survival probability.Conclusions: The assessment of serum NfL and p-Tau181 may provide a comprehensive view of FTLD, aiding in the differential diagnosis, in staging disease severity and in defining survival probability. [ABSTRACT FROM AUTHOR]

Objective: While metabolic dysfunction occurs in several pulmonary arterial hypertension (PAH) animal models, its role in the human hypertensive right ventricle (RV) and lung is not well characterised. We investigated whether circulating metabolite concentrations differ across the hypertensive RV and/or the pulmonary circulation, and correlate with invasive haemodynamic/echocardiographic variables in patients with PAH.Methods: Prospective EDTA blood collection during cardiac catheterisation from the superior vena cava (SVC), pulmonary artery (PA) and ascending aorta (AAO) in children with PAH (no shunt) and non-PAH controls (Con), followed by unbiased screens of 427 metabolites and 836 lipid species and fatty acids (FAs) in blood plasma (Metabolon and Lipidyzer platforms). Metabolite concentrations were correlated with echocardiographic and invasive haemodynamic variables.Results: Metabolomics/lipidomics analysis of differential concentrations (false discovery rate<0.15) revealed several metabolite gradients in the trans-RV (PA vs SVC) setting. Notably, dicarboxylic acids (eg, octadecanedioate: fold change (FC)_Control=0.77, FC_PAH=1.09, p value=0.044) and acylcarnitines (eg, stearoylcarnitine: FC_Control=0.74, FC_PAH=1.21, p value=0.058). Differentially regulated metabolites were also found in the transpulmonary (AAO vs PA) setting and between-group comparisons, that is, in the SVC (PAH-SVC vs Con-SVC), PA and AAO. Importantly, the differential PAH-metabolite concentrations correlated with numerous outcome-relevant variables (e.g., tricuspid annular plane systolic excursion, pulmonary vascular resistance).Conclusions: In PAH, trans-RV and transpulmonary metabolite gradients exist and correlate with haemodynamic determinants of clinical outcome. The most pronounced differential trans-RV gradients are known to be involved in lipid metabolism/lipotoxicity, that is, accumulation of long chain FAs. The identified accumulation of dicarboxylic acids and acylcarnitines likely indicates impaired β-oxidation in the hypertensive RV and represents emerging biomarkers and therapeutic targets in PAH. [ABSTRACT FROM AUTHOR]

Objective: Distinguishing early dilated cardiomyopathy (DCM) from physiological left ventricular (LV) dilatation with LV ejection fraction <55% in athletes (grey zone) is challenging. We evaluated the role of a cascade of investigations to differentiate these two entities.Methods: Thirty-five asymptomatic active males with DCM, 25 male athletes in the 'grey zone' and 24 male athletes with normal LV ejection fraction underwent N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement, ECG and exercise echocardiography. Grey-zone athletes and patients with DCM underwent cardiovascular magnetic resonance (CMR) and Holter monitoring.Results: Larger LV cavity dimensions and lower LV ejection fraction were the only differences between grey-zone and control athletes. None of the grey-zone athletes had abnormal NT-proBNP, increased ectopic burden/complex arrhythmias or pathological late gadolinium enhancement on CMR. These features were also absent in 71%, 71% and 50% of patients with DCM, respectively. 95% of grey-zone athletes and 60% of patients with DCM had normal ECG. During exercise echocardiography, 96% grey-zone athletes increased LV ejection fraction by >11% from baseline to peak exercise compared with 23% of patients with DCM (p<0.0001). Peak LV ejection fraction was >63% in 92% grey-zone athletes compared with 17% patients with DCM (p<0.0001). Failure to increase LV ejection fraction >11% from baseline to peak exercise or achieve a peak LV ejection fraction >63% had sensitivity of 77% and 83%, respectively, and specificity of 96% and 92%, respectively, for predicting DCM.Conclusion: Comprehensive assessment using a cascade of routine investigations revealed that exercise stress echocardiography has the greatest discriminatory value in differentiating between grey-zone athletes and asymptomatic patients with DCM. Our findings require validation in larger studies. [ABSTRACT FROM AUTHOR]

Objective: To explore whether HIV types 1 and 2 and CD4 cell count affect cervical neoplasia independent of human papillomavirus (HPV) in women with high or low numbers of sexual partners residing in Abidjan, Côte d'Ivoire.Methods: The study population and methods are described in the companion paper. Additional methods include a Papanicolaou smear for cytological diagnosis and statistical analysis.Results: In maternal women, both HIV-1 and high risk HPV were significant independent risk factors for squamous intraepithelial lesions (SIL) (adjusted odds ratio (OR) 11.0 (95% CI 1.1-112) and 5.4 (1.5-18.8), respectively). Only high levels of HPV DNA in the lavage were associated with SIL (OR 13.2 (3.6-47.8)) in the maternal group. In female sex workers, high risk HPV was significantly associated with SIL (OR 23.7 (4.4-126)); HIV seropositivity was not. Any positive level (high or low amounts) of HPV DNA was significantly associated with SIL in sex workers (ORs 15.9 (3.3-76) and 12.7 (3.6-44), respectively). There was no association of SIL with CD4 cell counts < or = 500 x 10(6)/l in HIV seropositive women from either group.Conclusion: HPV or HIV-1 infection independently affect cervical neoplasia in women with low numbers of sex partners. [ABSTRACT FROM AUTHOR]

The article presents information on a summary of a case control medical research published in the journal, which evaluates the effectiveness of pertussis vaccines in adolescents and adults. The study illustrates that the effect of acellular pertussis vaccines is abated eventually when given in childhood. This study included participants including both cases and controls from Kaiser Permanente Northern California, a healthcare delivery system.

The article inquires whether the use of benzodiazepines increases the risk of dementia in elderly people. It is revealed that over a 15 year follow-up period, starting treatment with benzodiazepines increased the risk of dementia by about 50 percent compared with non-users. Adjustment for factors strongly associated with starting benzodiazepines or considered to be markers for a prodrome of early dementia did not alter the association.

Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD.Methods: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset).Results: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs =-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival.Conclusion: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities. [ABSTRACT FROM AUTHOR]

Objective: Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment.Method: A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined.Results: Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531).Conclusion: VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy. [ABSTRACT FROM AUTHOR]