Measurement issues when assessing quality of life outcomes for different types of hernia mesh repair

INTRODUCTION: The NHS is required to collect data from patient reported outcome measures (PROMs) for inguinal hernia surgery. We explored the use of one such measure, the Carolinas Comfort Scale(®) (CCS), to compare long-term outcomes for patients who received two different types of mesh. The CCS questionnaire asks about mesh sensation, pain and movement limitations, and combines the answers into a total score. PATIENTS AND METHODS: A total of 684 patients were treated between January 2007 and August 2008 and were followed up in November 2009. RESULTS: Data on 215 patients who met the inclusion criteria were available (96 patients who received Surgipro™ mesh and 119 who received Parietene™ Progrip™ mesh). Recurrence rates were similar in the Surgipro™ group (2/96, 2.1%) and Progrip™ group (3/118, 2.5%) (Fisher's exact test = 1.0). Chronic pain occurred less frequently in the Surgipro™ group (11/95, 11.6%) than in the Progrip™ group (22/118, 18.6%) (p<0.157). Overall, 90% of CCS total scores indicated a good outcome (scores of 10 or less out of 115). A principal component analysis of the CCS found that responses clustered into two subscales: 'mesh sensation' and 'pain+movement limitations'. The Progrip™ group had a slightly higher mesh sensation score (p<0.051) and similar pain+movement limitations scores (p<0.120). CONCLUSIONS: In this study of quality of life outcomes related to different mesh types, the CCS subscales were more sensitive to differences in outcome than the total CCS score for the whole questionnaire. Future research should consider using the CCS subscales rather than the CCS total score

Free-of-charge medicine schemes in the NHS: A local and regional drug and therapeutic committee's experience

INTRODUCTION: Free-of-charge (FoC) medicine schemes are increasingly available and allow access to investigational treatments outside clinical trials or in advance of licensing or NHS commissioning. METHODS: We retrospectively reviewed FoC medicine schemes evaluated between 2013 and 2019 by a single NHS trust and a regional drug and therapeutics committee (DTC). The details of each locally reviewed FoC scheme, and any nationally available Medicines and Healthcare products Regulatory Agency Early Access to Medicines Scheme (MHRA EAMS) in the same period, were recorded and categorised. RESULTS: Most FoC schemes (95%) allowed access to medicines intended to address an unmet clinical need. Over 7 years, 90% were company-FoC schemes and 10% were MHRA EAMS that were locally reviewed. Phase 3 clinical trial data were available for 44% of FoC schemes, 37% had phase 2 data and 19% were supported only by phase 1 data, retrospective observational studies or preclinical data. Utilisation of company-FoC schemes increased on average by 50% per year, while MHRA EAMS schemes showed little growth. CONCLUSION: Company-FoC medicine schemes are increasingly common. This may indicate a preference for pharmaceutical companies to independently co-ordinate schemes. Motivations for company-FoC schemes remain unclear and many provide access to treatments that are yet to be evaluated in appropriately conducted clinical trials, and whose efficacy and risk of harm remain uncertain. There is no standardisation of this practice and there is no regulatory oversight. Moreover, no standardised data collection framework is in place that could demonstrate the utility of such programmes in addressing unmet clinical need or to allow generation of further evidence

A TARGETED LOAD-CARRIAGE TRAINING PROGRAM ELICITS POSITIVE ADAPTATIONS AFTER 10-WEEKS

The purpose of this study was to identify and characterise physical performance responses to a targeted 10-week load-carriage physical training intervention in males. Performance measures of maximal strength, heart rate, rating of perceived exertion, and basic fitness from nine male civilians before and after the 10-week training intervention are presented. There were significant increases in maximal force (~200 N) and aerobic performance (Level. Shuttle 8.9 vs 9,4 variables). Small-to-large effect sizes were shown for basic fitness and perceptual responses. The 10-week load-carriage physical training intervention elicited physical performance improvements and may facilitate load-carriage task performance

IMPROVEMENTS IN LOWER-LIMB STRENGTH ARE ASSOCIATED WITH HIP CONTROL DURING LOAD CARRIAGE IN FEMALES

The purpose of this study was to investigate the effect of lower-limb strength on lower-limb biomechanical responses over the duration of a load carriage march. Female civilians (n=12) completed a 5 km march at 5.5 km·h-1 wearing a 23 kg external load before and after 10 weeks of hip-focussed training. Lower-limb 3D kinematics were acquired during the march, with lower-limb strength measures assessed prior to pre- and post-training marching tasks. Significant increases in lower-limb strength were elicited after training, alongside moderate to strong negative correlations between strength and hip adduction (

Prostate cancer risk: associations with ultraviolet radiation, tyrosinase and melanocortin-1 receptor genotypes

Exposure to ultraviolet radiation may reduce prostate cancer risk, suggesting that polymorphism in genes that mediate host pigmentation will be associated with susceptibility to this cancer. We studied 210 prostate cancer cases and 155 controls to determine whether vitamin D receptor (VDR, Taql and Fokl variants), tyrosinase (TYR, codon 192 variant) and melanocortin-1 receptor (MC1R, Arg151Cys, Arg160Trp, Val92Met, Asp294His and Asp84Glu variants) genotypes are associated with risk. UV exposure was determined using a questionnaire. MC1R Arg160/Arg160 homozygotes were at increased risk (P = 0.027, odds ratio = 1.94) while TYR A2/A2 homozygotes were at reduced risk of prostate cancer (P = 0.033, odds ratio = 0.48). These associations remained significant after correction for UV-exposure. Stratification of cases and controls by quartiles of exposure, showed that the protective effect of TYR A1A2 (P = 0.006, odds ratio 0.075) and A2A2 (P = 0.003, odds ratio 0.055) was particularly strong in subjects who had received the greatest exposure. Our data show for the first time, that allelism in genes linked with skin pigment synthesis is associated with prostate cancer risk possibly because it mediates the protective effects of UV. Importantly, susceptibility is associated with an interaction between host predisposition and exposure. © 2001 Cancer Research Campaign  http://www.bjcancer.co

Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

This is the final version of the article. Available from Wiley via the DOI in this record.BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, β = 0.023, P = 0.01; highest, β = 0.021, P = 0.02), Digit Vigilance Task (lowest, β = 0.009, P = 0.05; highest, β = 0.01, P = 0.02) and Power of Attention (lowest, β = 0.017, P = 0.02; highest, β = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, β = 0.021, P = 0.02; highest, β = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.This work was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals Foundation Trust and Newcastle University (AG). The Newcastle 85+ Study has been funded by the Medical Research Council, Biotechnology and Biological Sciences Research Council and the Dunhill Medical Trust. Additional work has also been funded by the British Heart Foundation, Unilever Corporate Research, Newcastle University and National Health Service (NHS) North of Tyne (Newcastle Primary Care Trust). The views expressed in this paper are those of the authors and not necessarily those of the National Health Service, UK. We acknowledge the operational support of NHS North of Tyne, the local general practitioners and their staff, the research nurses, laboratory technicians, data management and clerical team, as well as many colleagues for their expert advice. Thanks are due especially to the study participants

Improving management of a mid-Atlantic coastal barrier island through assessment of habitat condition

AbstractTo achieve desired environmental outcomes, environmental condition and trends need to be rigorously measured and communicated to resource managers, scientists, and a broader general audience. However, there is often a disconnect between responsive ecosystem monitoring and decision making for strategic long-term management. This project demonstrates how historical monitoring data can be synthesized and used for future planning and decision making, thereby closing the management feedback cycle. This study linked disparate datasets, collected for a variety of purposes and across multiple temporal and spatial scales, in order to assess and quantify current habitat conditions. The results inform integrated resource management decision-making at Assateague Island National Seashore (Maryland and Virginia, USA) by using ecological reference conditions to identify monitoring needs, areas of high vulnerability, and areas with potential for improved management. The approach also provides a framework that can be applied in the future to assess the effectiveness of these management decisions on the condition of island habitats, and is a replicable demonstration of incorporating diverse monitoring datasets into an adaptive management cycle

An EMG-Assisted Muscle-Force Driven Finite Element Analysis Pipeline to Investigate Joint- and Tissue-Level Mechanical Responses in Functional Activities : Towards a Rapid Assessment Toolbox

Publisher Copyright: © 1964-2012 IEEE.Joint tissue mechanics (e.g., stress and strain) are believed to have a major involvement in the onset and progression of musculoskeletal disorders, e.g., knee osteoarthritis (KOA). Accordingly, considerable efforts have been made to develop musculoskeletal finite element (MS-FE) models to estimate highly detailed tissue mechanics that predict cartilage degeneration. However, creating such models is time-consuming and requires advanced expertise. This limits these complex, yet promising, MS-FE models to research applications with few participants and makes the models impractical for clinical assessments. Also, these previously developed MS-FE models have not been used to assess activities other than gait. This study introduces and verifies a semi-automated rapid state-of-the-art MS-FE modeling and simulation toolbox incorporating an electromyography- (EMG) assisted MS model and a muscle-force driven FE model of the knee with fibril-reinforced poro(visco)elastic cartilages and menisci. To showcase the usability of the pipeline, we estimated joint- and tissue-level knee mechanics in 15 KOA individuals performing different daily activities. The pipeline was verified by comparing the estimated muscle activations and joint mechanics to existing experimental data. To determine the importance of the EMG-assisted MS analysis approach, results were compared to those from the same FE models but driven by static-optimization-based MS models. The EMG-assisted MS-FE pipeline bore a closer resemblance to experiments compared to the static-optimization-based MS-FE pipeline. Importantly, the developed pipeline showed great potential as a rapid MS-FE analysis toolbox to investigate multiscale knee mechanics during different activities of individuals with KOA.Peer reviewe