The Strayed Reveller, No. 3

The third issue of The Strayed Revellerhttps://scholarworks.sfasu.edu/reveller/1002/thumbnail.jp

Comparing the performance of the novel FAMCAT algorithms and established case-finding criteria for familial hypercholesterolaemia in primary care

Objective Familial hypercholesterolaemia (FH) is a common inherited disorder causing premature coronary heart disease (CHD) and death. We have developed the novel Familial Hypercholesterolaemia Case Ascertainment Tool (FAMCAT 1) case-finding algorithm for application in primary care, to improve detection of FH. The performance of this algorithm was further improved by including personal history of premature CHD (FAMCAT 2 algorithm). This study has evaluated their performance, at 95% specificity, to detect genetically confirmed FH in the general population. We also compared these algorithms to established clinical case-finding criteria.Methods Prospective validation study, in 14 general practices, recruiting participants from the general adult population with cholesterol documented. For 260 participants with available health records, we determined possible FH cases based on FAMCAT thresholds, Dutch Lipid Clinic Network (DLCN) score, Simon-Broome criteria and recommended cholesterol thresholds (total cholesterol >9.0 mmol/L if ≥30 years or >7.5 mmol/L if ≤30 years), using clinical data from electronic and manual extraction of patient records and family history questionnaires. The reference standard was genetic testing. We examined detection rate (DR), sensitivity and specificity for each case-finding criteria.Results At 95% specificity, FAMCAT 1 had a DR of 27.8% (95% CI 12.5% to 50.9%) with sensitivity of 31.2% (95% CI 11.0% to 58.7%); while FAMCAT 2 had a DR of 45.8% (95% CI 27.9% to 64.9%) with sensitivity of 68.8% (95% CI 41.3% to 89.0%). DLCN score ≥6 points yielded a DR of 35.3% (95% CI 17.3% to 58.7%) and sensitivity of 37.5% (95% CI 15.2% to 64.6%). Using recommended cholesterol thresholds resulted in DR of 28.0% (95% CI 14.3% to 47.6%) with sensitivity of 43.8% (95% CI 19.8% to 70.1%). Simon-Broome criteria had lower DR 11.3% (95% CI 6.0% to 20.0%) and specificity 70.9% (95% CI 64.8% to 76.5%) but higher sensitivity of 56.3% (95% CI 29.9% to 80.2%).Conclusions In primary care, in patients with cholesterol documented, FAMCAT 2 performs better than other case-finding criteria for detecting genetically confirmed FH, with no prior clinical review required for case finding

Imposing compulsory rugby union on school children: An analysis of English state-funded secondary schools.

To establish the extent to which Rugby Union was a compulsory physical education activity in state-funded secondary schools in England and to understand the views of Subject Leaders for Physical Education with respect to injury risk. A cross-sectional research study using data obtained under the Freedom of Information Act (2000) from 288 state-funded secondary schools. Rugby Union was delivered in 81% ( = 234 of 288) of state-funded secondary school physical education curricula, including 83% ( = 229 of 275) of state-funded secondary school boys' and 54% ( = 151 of 282) of girls' physical education curricular. Rugby Union was compulsory in 91% ( = 208 of 229) of state-funded secondary schools that delivered it as part of the boys' physical education curriculum and 54% ( = 82 of 151) of state-funded secondary schools that delivered contact Rugby Union as part of the girls' physical education curriculum. Subject Leaders for Physical Education also perceived Rugby Union to have the highest risk of harm of the activities they delivered in their school physical education curriculum. Notwithstanding discussions of appropriate measures (i.e., mandatory concussion training, Rugby Union specific qualifications and CPD) to reduce injury risk, it is recommended that Rugby Union should not be a compulsory activity given that it has a perceived high risk of injury and is an unnecessary risk for children in physical education. [Abstract copyright: Copyright © 2022 White, Batten, Howarth, Magrath, Piggin, Millward, Parry, Lang, Bullingham, Pearce, Morales, Turner, Humphries, Hardwicke, Anderson, Kirkwood and Pollock.

Risk of cardiovascular disease outcomes in primary care subjects with familial hypercholesterolaemia: A cohort study

Background and aims: Familial hypercholesterolaemia (FH) is a known major cause of premature heart disease. However, the risks of atherosclerotic disease in other vascular regions are less known. We determined the risk of major cardiovascular disease (CVD) outcomes associated with clinical FH.Methods: In a retrospective cohort study (1 January, 1999 to 22 July, 2016), we randomly-matched 14,097 UK subjects with clinical FH diagnoses or characteristics (Simon-Broome definite or Dutch Lipid Clinic Score >8) to 42,506 subjects without FH by age, sex, general practice. We excluded those with CVD at baseline. Incident rates for coronary heart disease (CHD), stroke or transient ischaemic attack (TIA) and peripheral vascular disease (PVD) were estimated. Cox proportional hazards regression, stratified on matched-pairs, determined adjusted hazards ratios (HR) for incident CVD.Results: During follow-up (median 13.8 years), incidence rates (95% CI) of CVD (per 1000 person-years) were 25.6 (24.8–26.3) in FH and 2.9 (2.8–3.1) in non-FH subjects. The risk of CHD, stroke/TIA and PVD was higher in FH compared to non-FH subjects: CHD (HR 10.63, 95% CI 9.82–11.49), stroke/TIA (HR 6.74, 95% CI 5.84–7.77), PVD (HR 7.17, 95% CI 6.08–8.46). The risk of CVD was greater in those with FH characteristics (HR 13.52, 95% CI 12.48–14.65) than those with clinical diagnoses (HR 1.66, 95% CI 1.42–1.93).Conclusions: In addition to the recognised increased risk of CHD, subjects with FH have greatly elevated risk of stroke/TIA and PVD. This emphasises need for early diagnosis and preventive interventions beyond CHD, to reduce CVD risk in these individuals

Understanding Evolutionary Impacts of Seasonality: An Introduction to the Symposium

Seasonality is a critically important aspect of environmental variability, and strongly shapes all aspects of life for organisms living in highly seasonal environments. Seasonality has played a key role in generating biodiversity, and has driven the evolution of extreme physiological adaptations and behaviors such as migration and hibernation. Fluctuating selection pressures on survival and fecundity between summer and winter provide a complex selective landscape, which can be met by a combination of three outcomes of adaptive evolution: genetic polymorphism, phenotypic plasticity, and bet-hedging. Here, we have identified four important research questions with the goal of advancing our understanding of evolutionary impacts of seasonality. First, we ask how characteristics of environments and species will determine which adaptive response occurs. Relevant characteristics include costs and limits of plasticity, predictability, and reliability of cues, and grain of environmental variation relative to generation time. A second important question is how phenological shifts will amplify or ameliorate selection on physiological hardiness. Shifts in phenology can preserve the thermal niche despite shifts in climate, but may fail to completely conserve the niche or may even expose life stages to conditions that cause mortality. Considering distinct environmental sensitivities of life history stages will be key to refining models that forecast susceptibility to climate change. Third, we must identify critical physiological phenotypes that underlie seasonal adaptation and work toward understanding the genetic architectures of these responses. These architectures are key for predicting evolutionary responses. Pleiotropic genes that regulate multiple responses to changing seasons may facilitate coordination among functionally related traits, or conversely may constrain the expression of optimal phenotypes. Finally, we must advance our understanding of how changes in seasonal fluctuations are impacting ecological interaction networks. We should move beyond simple dyadic interactions, such as predator prey dynamics, and understand how these interactions scale up to affect ecological interaction networks. As global climate change alters many aspects of seasonal variability, including extreme events and changes in mean conditions, organisms must respond appropriately or go extinct. The outcome of adaptation to seasonality will determine responses to climate change

Case-finding and genetic testing for familial hypercholesterolaemia in primary care

Objective: Familial Hypercholesterolaemia (FH) is a common inherited disorder causing premature heart disease and death. We have developed novel case-finding algorithms (FAMCAT version 1 & 2) for application in primary care, to improve detection of FH and have evaluated their performance, at 95% specificity, to detect genetically-confirmed FH in the general population. We also compared these algorithms to established clinical case-finding criteria. Methods: Prospective validation study, in 14 general practices, recruiting participants from the general adult population with cholesterol documented. For 260 participants with available health records, we determined possible FH cases based on FAMCAT thresholds, Dutch Lipid Clinic Network (DLCN) score, Simon-Broome criteria and national recommended cholesterol thresholds (total cholesterol > 9.0 mmol/L if ≥30 years or > 7.5 mmol/L i

Comparison of coronary heart disease genetic assessment with conventional cardiovascular risk assessment in primary care: reflections on a feasibility study

This study assesses the feasibility of collecting genetic samples and self-reported outcome measures after cardiovascular risk assessment, and presenting the genetic test results to participants. Coronary heart disease (CHD) genetic tests are increasingly available through direct-to-consumer marketing, but their potential clinical impact on cardiovascular risk assessment is unclear. Observational study in 10 British general practices in Central England. A total of 320 individuals, who had completed conventional cardiovascular risk assessment, were offered CHD genetic test, with follow-up outcome questionnaire at eight months for lifestyle change and State-Trait Anxiety. A total of 119 (37%) participants returned genetic test specimens, with over a third reporting family history of CHD in a specified relative; 79 (66.4%) were categorized above-average risk on conventional cardiovascular risk assessment, 65 of whom (82.3%) were only average risk on genetic assessment. The dietary fat questionnaire was poorly completed while study participation was not associated with increased anxiety (mean increase in anxiety score=2.1; 95% CI −0.1–4.3; P=0.06). As a feasibility study, over a third of individuals offered genetic testing in primary care, as part of CVD risk assessment, took up the offer. Although intervention did not appear to increase anxiety, this needs further evaluation. To improve generalizability and effect size, future studies should actively engage individuals from wider socio-economic backgrounds who may not have already contemplated lifestyle change. The current research suggests general practitioners will face the clinical challenge of patients presenting with direct-to-consumer genetic results that are inconsistent with conventional cardiovascular risk assessment

Sex differences in cardiovascular morbidity associated with familial hypercholesterolaemia: A retrospective cohort study of the UK Simon Broome register linked to national hospital records

Background and aims: The UK Simon Broome (SB) familial hypercholesterolaemia (FH) register previously reported 3-fold higher standardised mortality ratio for cardiovascular disease (CVD) in women compared to men from 2009 to 2015. Here we examined sex differences in CVD morbidity in FH by national linkage of the SB register with Hospital Episode Statistics (HES).Methods: Of 3553 FH individuals in the SB register (aged 20-79 years at registration), 2988 (52.5% women) had linked HES records. Standardised Morbidity Ratios (SMbR) compared to an age and sex-matched UK general practice population were calculated [95% confidence intervals] for first CVD hospitalisation in HES (a composite of coronary heart disease (CHD), myocardial infarction (MI), stable or unstable angina, stroke, TIA, peripheral vascular disease (PVD), heart failure, coronary revascularisation interventions).Results: At registration, men had significantly (p50 years, SMbR was 33% higher in women than men (6.11 [5.57-6.70] vs 4.59 [4.08-5.15]).Conclusions: Excess CVD morbidity due to FH remains markedly elevated in women at all ages, but especially those aged 30-50 years. This highlights the need for earlier diagnosis and optimisation of lipid-lowering risk factor management for all FH patients, with particular attention to young women with FH

Mineral concentrations in bovine milk from farms with contrasting grazing management

Thirty conventional and 24 organic dairy farms were divided into equal-number within system groups: high-pasture, standard-pasture and low-pasture groups. Milk samples were collected monthly for 12 consecutive months. Milk from high-pasture organic farms contained less fat and protein than standard- and low-pasture organic farms, but more lactose than low-pasture organic farms. Pasture, concentrate feeds intakes and the contribution of non-Holstein breeds were the key drivers for these changes. Milk Ca and P concentrations were lower in standard-pasture conven-tional farms than the other conventional groups. Milk from low-pasture organic farms contained less Ca than high- and standard-pasture organic farms, while high-pasture organic farms produced milk with the highest Sn concentration. Differences in mineral concentrations were driven by the contribution of non-Holstein breeds, feeding practices, and grazing activity; due to relatively low numerical differences the subsequent impact on consumers’ mineral intakes would be minor

Imposing compulsory Rugby Union on schoolchildren: an analysis of English state-funded secondary schools

Objective: to establish the extent to which Rugby Union was a compulsory physical education activity in state-funded secondary schools in England and to understand the views of Subject Leaders for Physical Education with respect to injury risk. Method: a cross-sectional research study using data obtained under the Freedom of Information Act (2000) from 288 state-funded secondary schools. Results: Rugby Union was delivered in 81% (n = 234 of 288) of state-funded secondary school physical education curricula, including 83% (n = 229 of 275) of state-funded secondary school boys’ and 54% (n = 151 of 282) of girls’ physical education curricular. Rugby Union was compulsory in 91% (n = 208 of 229) of state-funded secondary schools that delivered it as part of the boys’ physical education curriculum and 54% (n = 82 of 151) of state-funded secondary schools that delivered contact Rugby Union as part of the girls’ physical education curriculum. Subject Leaders for Physical Education also perceived Rugby Union to have the highest risk of harm of the activities they delivered in their school physical education curriculum. Conclusion: Notwithstanding discussions of appropriate measures (i.e., mandatory concussion training, Rugby Union specific qualifications and CPD) to reduce injury risk, it is recommended that Rugby Union should not be a compulsory activity given that it has a perceived high risk of injury and is an unnecessary risk for children in physical education