Online data on opening hours of general practices in England: a comparison with telephone survey data

Background

The NHS Choices website (www.nhs.uk) provides data on the opening hours of general practices in England. If the data are accurate, they could be used to examine the benefits of extended hours.

Aim

To determine whether online data on the opening times of general practices in England are accurate regarding the number of hours in which GPs provide face-to-face consultations.

Design and setting

Cross-sectional comparison of data from NHS Choices and telephone survey data reported by general practice staff, for a nationally representative sample of 320 general practices (December 2013 to September 2014).

Method

GP face-to-face consultation times were collected by telephone for each sampled practice for each day of the week. NHS Choices data on surgery times were available online. Analysis was based on differences in the number of surgery hours (accounting for breaks) and the times of the first and last consultations of the day only between the two data sources.

Results

The NHS Choices data recorded 8.8 more hours per week than the survey data on average (40.1 versus 31.2; 95% confidence interval [CI] = 7.4 to 10.3). This was largely accounted for by differences in the recording of breaks between sessions. The data were more similar when only the first and last consultation times were considered (mean difference = 1.6 hours; 95% CI = 0.9 to 2.3).

Conclusion

NHS Choices data do not accurately measure the number of hours in which GPs provide face-to-face consultations. They better record the hours between the first and last consultations of the day.     

An exome sequencing strategy to diagnose lethal autosomal recessive disorders

Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0–4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies.     

Pathogenic mitochondrial mt-tRNAAla variants are uniquely associated with isolated myopathy

Pathogenic mitochondrial DNA (mtDNA) point mutations are associated with a wide range of clinical phenotypes, often involving multiple organ systems. We report two patients with isolated myopathy owing to novel mt-tRNA^Ala variants. Muscle biopsy revealed extensive histopathological findings including cytochrome c oxidase (COX)-deficient fibres. Pyrosequencing confirmed mtDNA heteroplasmy for both mutations (m.5631G>A and m.5610G>A) whilst single-muscle fibre segregation studies (revealing statistically significant higher mutation loads in COX-deficient fibres than in COX-positive fibres), hierarchical mutation segregation within patient tissues and decreased steady-state mt-tRNA^Ala levels all provide compelling evidence of pathogenicity. Interestingly, both patients showed very high-mutation levels in all tissues, inferring that the threshold for impairment of oxidative phosphorylation, as evidenced by COX deficiency, appears to be extremely high for these mt-tRNA^Ala variants. Previously described mt-tRNA^Ala mutations are also associated with a pure myopathic phenotype and demonstrate very high mtDNA heteroplasmy thresholds, inferring at least some genotype:phenotype correlation for mutations within this particular mt-tRNA gene.     

Overweight,obesity and the risk of LADA: results from a Swedish case–control study and the Norwegian HUNT Study

Aims/hypothesis

Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies.

Methods

Analyses were based on incident cases of LADA (n?=?425) and type 2 diabetes (n?=?1420), and 1704 randomly selected control participants from a Swedish case–control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984–2008). We present adjusted ORs and HRs with 95% CI.

Results

In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD.

Conclusions/interpretation

Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.

     

Juvenile rhesus monkeys have lower type 2 cytokine responses than adults after primary infection with Schistosoma mansoni

Adults and children have differences in their susceptibility to schistosomiasis. The relative influences of age-dependent innate resistance and acquired immunity in the differences between susceptibility to schistosomiasis are difficult to assess in humans. Therefore, we exposed juvenile and adult female rhesus monkeys to primary infection with Schistosoma mansoni. In contrast to the adult animals, the juvenile rhesus monkeys had low levels of interleukin (IL)-4 and IL-5 production by peripheral blood mononuclear cells after schistosome infection, as well as lower levels of parasite-antigen-specific antibody (IgG, IgM, and IgA) responses, and produced limited antigen-specific or total IgE. Juvenile animals had statistically nonsignificant increased worm burdens and tissue or fecal egg counts, compared with that of adults, whereas circulating schistosome antigens were significantly higher in infected juvenile monkeys. These results suggest that juvenile rhesus monkeys have reduced type 2 cytokine responses after primary schistosome infections and perhaps are more susceptible to parasite infection.     

Fibrinogen and Fibrin Clot Structure in Diabetes

Diabetes is associated with an increased risk of developing cardiovascular disease, which is not fully accounted for by the accumulation of classic cardiovascular risk factors in patients. Recent evidence has demonstrated fibrinogen to be a powerful independent risk marker for cardiovascular disease in the general population, and it is also likely to contribute toward the increased atherosclerotic risk in diabetes. The etiology of hyperfibrinogenemia in diabetes is likely to be multifactorial, and at present the mechanisms involved have not been clarified. However, insulin, insulin resistance and inflammation are likely to be involved, especially in type 2 diabetes. The influence of diabetes in determining an individual's atherothrombotic risk is likely to extend beyond that of elevated fibrinogen levels, and may also act via changes in the structure and function of the fibrin clot that forms. Further research is needed to determine the mechanisms underlying these changes, which may lead to development of future interventions to reduce the excessive vascular risk associated with this disease.     

Differences in outcomes between the JoyBar control and standard wheelchair joystick control on two maneuverability tasks: a pilot study

Purpose: To determine if older adult, novice wheelchair users who drive a power wheelchair with a JoyBar control complete maneuverability tasks in less time and with less error than those who drive a power wheelchair with a standard joystick control.

Materials and methods: A parallel randomized controlled trial design conducted at a medical rehabilitation and research centre with ambulatory older adults aged 60 and above (n?=?27). The intervention was the JoyBar alternative wheelchair control. The primary outcome measure was total time to complete each of the two maneuverability tasks. The secondary outcome measure was total number of errors during each of the maneuverability tasks.

Results: An independent, two sampled t-test was conducted and revealed that the JoyBar group took a greater amount of time to complete both maneuverability tasks than the control group (p?p?Conclusions: Maneuverability of a powered wheelchair by novice wheelchair users was not improved through the use of the JoyBar when compared to a standard wheelchair joystick, as measured by rates of error and time to complete maneuverability tasks.

• Implications for rehabilitation

• Clients who are new to powered wheelchair use may perform maneuverability tasks faster, with equivalent accuracy, using a standard joystick versus the JoyBar.

• Clients who use a JoyBar may require adjustments to the programming of their wheelchair to ensure optimal performance.

• Additional training may be required to achieve proficiency in maneuverability tasks with a JoyBar versus a standard joystick.