Crash characteristics and injury outcomes for older passenger car occupants

For some time now, it has been recognised that a major shift is occurring in the population age distributions of most motorised countries resulting in a growing number of older persons with an increasing need for mobility. It is expected that the mobility of older persons will become even more reliant on the motor vehicle as European countries in particular undergo transitions towards decentralisation and suburbanisation and because of the well-established longevity factor. This study compares injury outcomes in passenger car crashes for belted occupants of different ages. The study considers drivers and front seat passengers. National accident data in the UK show that whilst older car occupants are less likely to be involved in a car accident than younger occupants, in the event of a crash, older occupants are more likely to be killed or to sustain serious injury. This, in conjunction with the increasing numbers of older licence holder and car users implies that the protection of the inherently frail elderly should become a priority for the future. Analysis of the UK in-depth accident data revealed that the older car occupants were significantly more prone to serious chest injury than their younger counterparts and that these injuries were predominantly due to forces exerted by the restraint system, particularly in frontal impacts. Since by the year 2030 one in four persons will be aged over 65 in most Organisation for Economic Cooperation and Development (OECD) countries, the results suggest a need for intervention through vehicle design including in-vehicle crashworthiness systems that take into account the reduced tolerance to impact that occurs with ageing

An overview of requirements for the crash protection of older drivers

For some time now, it has been recognised that a major shift is occurring in the population age distributions of most motorised countries resulting in a growing number of older persons with an increasing need for mobility. It is expected that the mobility of older persons will become even more reliant on the motor vehicle as European countries in particular undergo transitions towards decentralisation and suburbanisation and because of the well-established longevity factor. As a group, older drivers do not currently represent a major road safety problem in most Western societies when compared with other age groups such as the young. However, they are involved in significantly more serious injury and casualty crashes per head of population. Furthermore, as older drivers are likely to become a more significant problem in the years ahead, it is now necessary to examine some vehicle design factors that affect the safety of the older driver in a crash

Vehicle crashworthiness and the older motorist

This study examines the relationship between age and the injury outcomes for belted drivers in road vehicle crashes in the United Kingdom. The sample of 1,541 drivers was divided into three age groups: 889 drivers were aged 17–39 years (young drivers) ; 515 were 40–64 years (middle-aged), and 137 aged 65–84 years (older drivers). Both frontal and side impact crashes in which the vehicles sustained sufficient damage to be towed away from the scene are considered. Indepth information obtained from examinations of the crashed vehicles was combined with clinical data obtained from hospitals to throw light on the mechanisms that led to the injuries. Results show that in crashes of approximately equal severity, older drivers were significantly more likely than middle-aged and young drivers to be fatally injured in both frontal ( p<0.001) and side ( p<0.05) impact crashes. The results also show that older drivers sustained more injuries to the chest ( p<0.0001) and that this body region is particularly problematic. The main sources of the chest injuries were found to be the seat belt in frontal crashes and the door in side impact crashes. As the number of older car users will increase rapidly in most OECD countries in the coming decades, the results suggest that vehicle re-designs are required, including in-vehicle crashworthiness systems, to take into account older people’s relatively low tolerance of crash impacts

Availability and structure of primary medical care services and population health and health care indicators in England

BACKGROUND: It has been proposed that greater availability of primary medical care practitioners (GPs) contributes to better population health. We evaluated whether measures of the supply and structure of primary medical services are associated with health and health care indicators after adjusting for confounding. METHODS: Data for the supply and structure of primary medical services and the characteristics of registered patients were analysed for 99 health authorities in England in 1999. Health and health care indicators as dependent variables included standardised mortality ratios (SMR), standardised hospital admission rates, and conceptions under the age of 18 years. Linear regression analyses were adjusted for Townsend score, proportion of ethnic minorities and proportion of social class IV/ V. RESULTS: Higher proportions of registered rural patients and patients ≥ 75 years were associated with lower Townsend deprivation scores, with larger partnership sizes and with better health outcomes. A unit increase in partnership size was associated with a 4.2 (95% confidence interval 1.7 to 6.7) unit decrease in SMR for all-cause mortality at 15–64 years (P = 0.001). A 10% increase in single-handed practices was associated with a 1.5 (0.2 to 2.9) unit increase in SMR (P = 0.027). After additional adjustment for percent of rural and elderly patients, partnership size and proportion of single-handed practices, GP supply was not associated with SMR (-2.8, -6.9 to 1.3, P = 0.183). CONCLUSIONS: After adjusting for confounding with health needs of populations, mortality is weakly associated with the degree of organisation of practices as represented by the partnership size but not with the supply of GPs

The Use of Herbal Medications and Dietary Supplements by People with Mental Illness

This study examined the relationship between herbal medication and dietary supplement (HMDS) use and mental health characteristics. Data are drawn from a national household survey of the United States’ civilian, non-institutionalized population (N = 9,585). Psychiatric medication and HMDS use, psychiatric diagnoses and treatment needs, utilization and satisfaction were assessed. Compared to non-users, HMDS users were more likely to perceive themselves as having mental health needs, to have received mental health and primary care treatment, and to be dissatisfied with their overall healthcare. Psychiatric medication use was not related to HMDS use, and in multivariate analyses, HMDS use was associated with perceived mental health needs. Differences in use of specific HMDS between those with and without a psychiatric disorder were also examined. The use of HMDS warrants particular attention in persons with perceived mental health problems as these individuals may be turning to HMDS use for treatment of their symptoms

Mutation screening of retinal dystrophy patients by targeted capture from tagged pooled DNAs and next generation sequencing.

Purpose: Retinal dystrophies are genetically heterogeneous, resulting from mutations in over 200 genes. Prior to the development of massively parallel sequencing, comprehensive genetic screening was unobtainable for most patients. Identifying the causative genetic mutation facilitates genetic counselling, carrier testing and prenatal/pre-implantation diagnosis, and often leads to a clearer prognosis. In addition, in a proportion of cases, when the mutation is known treatment can be optimised and patients are eligible for enrolment into clinical trials for gene-specific therapies. Methods: Patient genomic DNA was sheared, tagged and pooled in batches of four samples, prior to targeted capture and next generation sequencing. The enrichment reagent was designed against genes listed on the RetNet database (July 2010). Sequence data were aligned to the human genome and variants were filtered to identify potential pathogenic mutations. These were confirmed by Sanger sequencing. Results: Molecular analysis of 20 DNAs from retinal dystrophy patients identified likely pathogenic mutations in 12 cases, many of them known and/or confirmed by segregation. These included previously described mutations in ABCA4 (c.6088C>T,p.R2030*; c.5882G>A,p.G1961E), BBS2 (c.1895G>C,p.R632P), GUCY2D (c.2512C>T,p.R838C), PROM1 (c.1117C>T,p.R373C), RDH12 (c.601T>C,p.C201R; c.506G>A,p.R169Q), RPGRIP1 (c.3565C>T,p.R1189*) and SPATA7 (c.253C>T,p.R85*) and new mutations in ABCA4 (c.3328+1G>C), CRB1 (c.2832_2842+23del), RP2 (c.884-1G>T) and USH2A (c.12874A>G,p.N4292D). Conclusions: Tagging and pooling DNA prior to targeted capture of known retinal dystrophy genes identified mutations in 60% of cases. This relatively high success rate may reflect enrichment for consanguineous cases in the local Yorkshire population, and the use of multiplex families. Nevertheless this is a promising high throughput approach to retinal dystrophy diagnostics

Persistence of immune response in heterologous COVID vaccination schedules in the Com-COV2 study - a single-blind, randomised trial incorporating mRNA, viral-vector and protein-adjuvant vaccines

BACKGROUND: Heterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development. METHODS: Com-COV2 was a single-blinded trial in which adults ≥50 years, previously immunised with single dose 'ChAd' (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or 'BNT' (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 1:1:1 to receive a second dose 8-12 weeks later with either the homologous vaccine, or 'Mod' (mRNA-1273, Spikevax, Moderna) or 'NVX' (NVX-CoV2373, Nuvaxovid, Novavax). Immunological follow-up and the secondary objective of safety monitoring were performed over nine months. Analyses of antibody and cellular assays were performed on an intention-to-treat population without evidence of COVID-19 infection at baseline or for the trial duration. FINDINGS: In April/May 2021, 1072 participants were enrolled at a median of 9.4 weeks after receipt of a single dose of ChAd (N= 540, 45% female) or BNT (N=532, 39% female) as part of the national vaccination programme. In ChAd-primed participants, ChAd/Mod had the highest anti-spike IgG from day 28 through to 6 months, although the heterologous vs homologous geometric mean ratio (GMR) dropped from 9.7 (95%CI: 8.2,11.5) at D28 to 6.2 (95%CI: 5.0, 7.7) at D196. The heterologous/homologous GMR for ChAd/NVX similarly dropped from 3.0 (95%CI:2.5-3.5) to 2.4 (95%CI:1.9-3.0). In BNT-primed participants, decay was similar between heterologous and homologous schedules with BNT/Mod inducing the highest anti-spike IgG for the duration of follow-up. The aGMR for BNT/Mod compared with BNT/BNT increased from 1.36 (95%CI: 1.17, 1.58) at D28 to 1.52 (95%CI: 1.21, 1.90) at D196, whilst for BNT/NVX this aGMR was 0.55 (95%CI: 0.47, 0.64) at day 28 and 0.62 (95%CI: 0.49, 0.78) at day 196. Heterologous ChAd-primed schedules produced and maintained the largest T-cell responses until D196. Immunisation with BNT/NVX generated a qualitatively different antibody response to BNT/BNT, with the total IgG significantly lower than BNT/BNT during all follow-up time points, but similar levels of neutralising antibodies. INTERPRETATION: Heterologous ChAd-primed schedules remain more immunogenic over time in comparison to ChAd/ChAd. BNT-primed schedules with a second dose of either mRNA vaccine also remain more immunogenic over time in comparison to BNT/NVX. The emerging data on mixed schedules using the novel vaccine platforms deployed in the COVID-19 pandemic, suggest that heterologous priming schedules might be considered as a viable option sooner in future pandemics. ISRCTN: 27841311 EudraCT:2021-001275-16 FUNDING: UK Vaccine Task Force (VTF), Coalition for Epidemic Preparedness Innovations (CEPI) and National Institute for Health and Carte Research (NIHR). NVX was supplied for trial use by Novavax, Inc

Characterization and Genomic Localization of a SMAD4 Processed Pseudogene

Like many clinical diagnostic laboratories, we undertake routine investigation of cancer-predisposed individuals by high-throughput sequencing of patient DNA that has been target-enriched for genes associated with hereditary cancer. Accurate diagnosis using such reagents requires alertness against rare nonpathogenic variants that may interfere with variant calling. In a cohort of 2042 such cases, we identified five that initially appeared to be carriers of a 95-bp deletion of SMAD4 intron 6. More detailed analysis indicated that these individuals all carried one copy of a SMAD4 processed gene. Because of its interference with diagnostic analysis, we characterized this processed gene in detail. Whole genome sequencing and confirmatory Sanger sequencing of junction PCR products were used to show that in each of the five cases, the SMAD4 processed gene was integrated at the same position on chromosome 9, located within the last intron of the SCAI gene. This rare polymorphic processed gene therefore reflects the occurrence of a single ancestral retrotransposition event. Compared to the reference SMAD4 mRNA sequence NM_005359.5 (https://www.ncbi.nlm.nih.gov/nucleotide/), the 5′ and 3′ UTR regions of the processed gene are both truncated, but its open reading frame is unaltered. Our experience leads us to advocate the use of an RNA-seq aligner, as part of diagnostic assay quality assurance, since this allows their recognition in a comparatively facile automated fashion