45 research outputs found
Human rhinoviruses: coming in from the cold
Rhinovirus infections cause at least 70% of virus-related wheezing exacerbations and cold and flu-like illnesses. Infections are also associated with otitis media, sinusitis and pneumonia. The annual impact of human rhinovirus (HRV) infections costs billions of healthcare dollars. To date, 100 serotyped HRV or 'classical' strains have been divided between two genetically distinct species based on subgenomic sequences, but many more, apparently novel strains remain un-characterized, circulating in unknown patterns and causing undefined illnesses. Until recently, the genomes of less than half the classical strains had been sequenced. In April 2009, the remaining classical HRV genome sequences were reported. These data will inform therapeutic development and phylogenetic analysis for this subset of HRV strains but should be viewed as one step in a long road leading to comprehensive HRV characterization
The role of Neuropilin-1 in COVID-19
Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae
Usefulness of Published PCR Primers in Detecting Human Rhinovirus Infection
We conducted a preliminary comparison of the relative sensitivity of a cross-section of published human rhinovirus (HRV)βspecific PCR primer pairs, varying the oligonucleotides and annealing temperature. None of the pairs could detect all HRVs in 2 panels of genotyped clinical specimens; >1 PCR is required for accurate description of HRV epidemiology
The cost-effectiveness of exercise-based cardiac rehabilitation:a systematic review of the characteristics and methodological quality of published literature
Aim:
This descriptive review aimed to assess the characteristics and methodological quality of economic
evaluations of cardiac rehabilitation (CR) programs according to updated economic guidelines for
healthcare interventions. Recommendations will be made to inform future research addressing the impact
of a physical exercise component on cost-effectiveness.
Methods:
Electronic databases were searched for economic evaluations of exercise-based CR programs published in
English between 2000 and 2014. The Consolidated Health Economic Evaluation Reporting Standards
(CHEERS) statement was used to review the methodological quality of included economic evaluations.
Results:
Fifteen economic evaluations met the review inclusion criteria. Assessed study characteristics exhibited
wide variability, particularly in their economic perspective, time horizon, setting, comparators and included
costs, with significant heterogeneity in exercise dose across interventions. Ten evaluations were based on
randomised controlled trials (RCTs) spanning 6-24 months but often with weak or inconclusive results; two
were modelling studies; and the final three utilised longer time horizons of 3.5-5 years from which findings
suggest that long-term exercise-based CR results in lower costs, reduced hospitalisations and a longer
cumulative patient lifetime. None of the 15 articles met all the CHEERS quality criteria, with the majority
either fully or partially meeting a selection of the assessed variables.
Conclusion:
Evidence exists supporting the cost-effectiveness of exercise-based CR for cardiovascular disease patients.
However, variability in CR program delivery and weak consistency between study perspective and design
limits study comparability and therefore the accumulation of evidence in support of a particular exercise
regime. The generalisability of study findings was limited due to the exclusion of patients with
comorbidities as would typically be found in a real-world setting. The use of longer time-horizons would be
more comparable with a chronic condition and enable economic assessments of the long-term effects of
CR. As none of the articles met recent reporting standards for the economic assessment of healthcare
interventions, it is recommended that future studies adhere to such guidelines
Co-circulation of Four Human Coronaviruses (HCoVs) in Queensland Children with Acute Respiratory Tract Illnesses in 2004
Acute respiratory illnesses (ARIs) with unconfirmed infectious aetiologies peak at different times of the year. Molecular diagnostic assays reduce the number of unconfirmed ARIs compared to serology- or culture-based techniques. Screening of 888 inpatient and outpatient respiratory specimens spanning late autumn through to early spring, 2004, identified the presence of a human coronavirus (HCoV) on 74 occasions (8.3% of all specimens and 26.3% of all respiratory virus detections). Prevalence peaked in August (late winter in the southern hemisphere) when they were detected in 21.9% of specimens tested. HCoV-HKU1 and HCoV-OC43 comprised 82.4% of all HCoVs detected. Positive specimens were used to develop novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. An objective clinical severity score was assigned to each positive HCoV patient. Severity scores were similar to those from a random selection of young children who were positive for respiratory syncytial virus at a different time but from the same specimen population. During the cooler months of 2004, sensitive and specific RT-rtPCRs identified the concurrent circulation of all four HCoVs, a quarter of which co-occurred with another virus and most of which were from children under the age of two years
Treatment of first-time traumatic anterior shoulder dislocation:the UK TASH-D cohort study
Background
Shoulder dislocations are the most common joint dislocations seen in emergency departments. Most traumatic cases are anterior and cause recurrent dislocations. Management options include surgical and conservative treatments. There is a lack of evidence about which method is most effective after the first traumatic anterior shoulder dislocation (TASD).
Objectives
To produce UK age- and sex-specific incidence rates for TASD. To assess whether or not surgery within 6 months of a first-time TASD decreases re-dislocation rates compared with no surgery. To identify clinical predictors of recurrent dislocation.
Design
A population-based cohort study of first-time TASD patients in the UK. An initial validation study and subsequent propensity-score-matched analysis to compare re-dislocation rates between surgery and no surgery after a first-time TASD. Prediction modelling was used to identify potential predictors of recurrent dislocation.
Setting
UK primary and secondary care data.
Participants
Patients with a first-time TASD between 1997 and 2015.
Interventions
Stabilisation surgery within 6 months of a first-time TASD (compared with no surgery). Stabilisation surgery within 12 months of a first-time TASD was also carried out as a sensitivity analysis.
Main outcome measures
Re-dislocation rate up to 2 years after the first TASD.
Methods
Eligible patients were identified from the Clinical Practice Research Datalink (CPRD) (1997β2015). Accuracy of shoulder dislocation coding was internally validated using the CPRD General Practitioner questionnaire service. UK age- and sex-specific incidence rates for TASD were externally validated against rates from the USA and Canada. A propensity-score-matched analysis using linked CPRD and Hospital Episode Statistics (HES) data compared re-dislocation rates for patients aged 16β35 years, comparing surgery with no surgery. Multivariable Cox regression models for predicting re-dislocation were developed for the surgical and non-surgical cohorts.
Results
Shoulder dislocation was coded correctly for 89% of cases in the CPRD [95% confidence interval (CI) 83% to 95%], with a βprimaryβ dislocation confirmed for 76% of cases (95% CI 67% to 85%). Far fewer patients than expected received stabilisation surgery within 6 months of a first TASD, leading to an underpowered study. Around 20% of re-dislocation rates were observed for both surgical and non-surgical patients. The sensitivity analysis at 12 months also showed little difference in re-dislocation rates. Missing data on risk factors limited the value of the prediction modelling; however, younger age, epilepsy and sex (male) were identified as statistically significant predictors of re-dislocation.
Limitations
Far fewer than the expected number of patients had surgery after a first-time TASD, resulting in an underpowered study. This and residual confounding from missing risk factors mean that it is not possible to draw valid conclusions.
Conclusions
This study provides, for the first time, UK data on the age- and sex-specific incidence rates for TASD. Most TASD occurs in men, but an unexpected increased incidence was observed in women aged >β50 years. Surgery after a first-time TASD is uncommon in the NHS. Re-dislocation rates for patients receiving surgery after their first TASD are higher than previously expected; however, important residual confounding risk factors were not recorded in NHS primary and secondary care databases, thus preventing useful recommendations.
Future work
The high incidence of TASD justifies investigation into preventative measures for young men participating in contact sports, as well as investigating the risk factors in women aged >β50 years. A randomised controlled trial would account for key confounders missing from CPRD and HES data. A national TASD registry would allow for a more relevant data capture for this patient group
Incidence of shoulder dislocations in the UK, 1995-2015 : a population-based cohort study
OBJECTIVE: This cohort study evaluates the unknown age-specific and gender-specific incidence of primary shoulder dislocations in the UK. SETTING: UK primary care data from the Clinical Practice Research Datalink (CPRD) were used to identify patients aged 16-70 years with a shoulder dislocation during 1995-2015. Coding of primary shoulder dislocations was validated using the CPRD general practitioner questionnaire service. PARTICIPANTS: A cohort of 16β763 patients with shoulder dislocation aged 16-70 years during 1995-2015 were identified. PRIMARY OUTCOME MEASURE: Incidence rates per 100β000 person-years and 95% CIs were calculated. RESULTS: Correct coding of shoulder dislocation within CPRD was 89% (95% CI 83% to 95%), and confirmation that the dislocation was a 'primary' was 76% (95% CI 67% to 85%). Seventy-two percent of shoulder dislocations occurred in men. The overall incidence rate in men was 40.4 per 100β000 person-years (95%βCI 40.4 to 40.4), and in women was 15.5 per 100β000 person-years (95%βCI 15.5 to 15.5). The highest incidence was observed in men aged 16-20βyears (80.5 per 100β000 person-years; 95%βCI 80.5 to 80.6). Incidence in women increased with age to a peak of 28.6 per 100β000 person-years among those aged 61-70 years. CONCLUSIONS: This is the first time the incidence of shoulder dislocations has been studied using primary care data from a national database, and the first time the results for the UK have been produced. While most primary dislocations occurred in young men, an unexpected finding was that the incidence increased in women aged over 50 years, but not in men. The reasons for this are unknown. Further work is commissioned by the National Institute for Health Research to examine treatments and predictors for recurrent shoulder dislocation. STUDY REGISTRATION: The design of this study was approved by the Independent Scientific Advisory Committee (15_260) for the Medicines & Healthcare products Regulatory Agency
Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.
Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations
Early Priming Minimizes the Age-Related Immune Compromise of CD8+ T Cell Diversity and Function
The elderly are particularly susceptible to influenza A virus infections, with increased occurrence, disease severity and reduced vaccine efficacy attributed to declining immunity. Experimentally, the age-dependent decline in influenza-specific CD8+ T cell responsiveness reflects both functional compromise and the emergence of βrepertoire holesβ arising from the loss of low frequency clonotypes. In this study, we asked whether early priming limits the time-related attrition of immune competence. Though primary responses in aged mice were compromised, animals vaccinated at 6 weeks then challenged >20 months later had T-cell responses that were normal in magnitude. Both functional quality and the persistence of βpreferredβ TCR clonotypes that expand in a characteristic immunodominance hierarchy were maintained following early priming. Similar to the early priming, vaccination at 22 months followed by challenge retained a response magnitude equivalent to young mice. However, late priming resulted in reduced TCRΞ² diversity in comparison with vaccination earlier in life. Thus, early priming was critical to maintaining individual and population-wide TCRΞ² diversity. In summary, early exposure leads to the long-term maintenance of memory T cells and thus preserves optimal, influenza-specific CD8+ T-cell responsiveness and protects against the age-related attrition of naΓ―ve T-cell precursors. Our study supports development of vaccines that prime CD8+ T-cells early in life to elicit the broadest possible spectrum of CD8+ T-cell memory and preserve the magnitude, functionality and TCR usage of responding populations. In addition, our study provides the most comprehensive analysis of the aged (primary, secondary primed-early and secondary primed-late) TCR repertoires published to date