Impact of the COVID-19 pandemic on prescription refills for immune-mediated inflammatory disorders:a time series analysis (January 2019 to January 2021) using the English Prescribing Dataset

OBJECTIVE: To investigate monthly prescription refills for common immunosuppressive/immunomodulatory therapy (sulfasalazine, hydroxychloroquine, azathioprine, methotrexate, leflunomide) prescriptions in England during the complete first wave of the COVID-19 pandemic. Secondary analysis examined unit cost analysis and regional use. DESIGN AND SETTING: A national cohort of community-based, primary care patients who anonymously contribute data to the English Prescribing Dataset, dispensed in the community in England, were included. Descriptive statistics and interrupted time series analysis over 25 months (14 months before, 11 months after first lockdown) were evaluated (January 2019 to January 2021, with March 2020 as the cut-off point). OUTCOME MEASURES: Prescription reimbursement variance in period before the pandemic as compared with after the first lockdown. RESULTS: Fluctuation in monthly medicines use is noted in March 2020: a jump is observed for hydroxychloroquine (Mann-Whitney, SE 14.652, standardised test statistic 1.911, p value=0.059) over the study period. After the first lockdown, medicines use fluctuated, with wide confidence intervals. Unit-cost prices changed substantially: sulfasalazine 33% increase, hydroxychloroquine 98% increase, azathioprine 41% increase, methotrexate 41% increase, leflunomide 20% decrease. London showed the least quantity variance, suggesting more homogeneous prescribing and patient access compared with Midlands and East of England, suggesting that some patients may have received medication over/under requirement, representing potential resource misallocation and a proxy for adherence rates. Changepoint detection revealed four out of the five medicines’ use patterns changed with a strong signal only for sulfasalazine in March/April 2020. CONCLUSIONS: Findings potentially present lower rates of adherence because of the pandemic, suggesting barriers to care access. Unit price increases are likely to have severe budget impacts in the UK and potentially globally. Timely prescription refills for patients taking immunosuppressive/immunomodulatory therapies are recommended. Healthcare professionals should identify patients on these medicines and assess their prescription-day coverage, with planned actions to flag and follow-up adherence concerns in patients

Extending mixtures of factor models using the restricted multivariate skew-normal distribution

The mixture of factor analyzers (MFA) model provides a powerful tool for analyzing high-dimensional data as it can reduce the number of free parameters through its factor-analytic representation of the component covariance matrices. This paper extends the MFA model to incorporate a restricted version of the multivariate skew-normal distribution for the latent component factors, called mixtures of skew-normal factor analyzers (MSNFA). The proposed MSNFA model allows us to relax the need of the normality assumption for the latent factors in order to accommodate skewness in the observed data. The MSNFA model thus provides an approach to model-based density estimation and clustering of high-dimensional data exhibiting asymmetric characteristics. A computationally feasible Expectation Conditional Maximization (ECM) algorithm is developed for computing the maximum likelihood estimates of model parameters. The potential of the proposed methodology is exemplified using both real and simulated data. (C) 2015 Elsevier Inc. All rights reserved

Subcutaneous nerve activity and mechanisms of sudden death in a rat model of chronic kidney disease

BACKGROUND: The mechanisms of sudden death in chronic kidney disease (CKD) remain unclear. OBJECTIVE: The purpose of this study was to test the hypotheses that subcutaneous nerve activity (SCNA) can be used to estimate sympathetic tone in ambulatory rats and that abrupt reduction of SCNA precedes the spontaneous arrhythmic death of Cy/+ rats. METHODS: Radiotransmitters were implanted in ambulatory normal (N = 6) and Cy/+ (CKD; N = 6) rats to record electrocardiogram and SCNA. Two additional rats were studied before and after chemical sympathectomy with 6-hydroxydopamine. RESULTS: In normal rats, the baseline heart rate (HR) and SCNA were 351 ± 29 bpm and 5.12 ± 2.97 mV·s, respectively. SCNA abruptly increased HR by 4.31% (95% confidence interval 4.15%-4.47%). In comparison, the CKD rats had reduced baseline HR (336 ± 21 bpm, P < .01) and SCNA (4.27 ± 3.19 mV·s, P < .01). When SCNA was observed, HR increased by only 2.48% (confidence interval 2.29%-2.67%, P < .01). All Cy/+ rats died suddenly, preceded by sinus bradycardia, advanced (second- and third-degree) AV block (N = 6), and/or ventricular tachycardia or fibrillation (N = 3). Sudden death was preceded by a further reduction of SCNA (3.22 ± 2.86 mV·s, P < .01) and sinus bradycardia (243 ± 55 bpm, P < .01). Histologic studies in CKD rats showed myocardial calcification that involved the conduction system. Chemical sympathectomy resulted in progressive reduction of SCNA over 7 days. CONCLUSION: SCNA can be used to estimate sympathetic tone in ambulatory rats. CKD is associated with reduced HR response to SCNA and conduction system diseases. Abrupt reduction of sympathetic tone precedes AV block, ventricular arrhythmia, and sudden death of CKD rats

Characterising risk of non-steroidal-anti-inflammatory drug related acute kidney injury: a retrospective cohort study

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAID complications include acute kidney injury (AKI), causing burden to patients and health services through increased morbidity, mortality, and hospital admissions. AIM: To measure the extent of NSAID prescribing in an adult population, the degree to which patients with potential higher risk of AKI were exposed to NSAIDs, and to quantify their risk of AKI. DESIGN & SETTING: Retrospective 2-year closed-cohort study. METHOD: A retrospective cohort of adults was identified from a pseudonymised electronic primary care database in Hampshire, UK. The cohort had clinical information, prescribing data, and complete GP- and hospital-ordered biochemistry data. NSAID exposure (minimum one prescription in a 2-month period) was categorised as never, intermittent, and continuous, and first AKI using the national AKI e-alert algorithm. Descriptive statistics and logistic regression were used to explore NSAID prescribing patterns and AKI risk. RESULTS: The baseline population was 702 265. NSAID prescription fell from 19 364 (2.8%) to 16 251 (2.4%) over 2 years. NSAID prescribing was positively associated with older age, female sex, greater socioeconomic deprivation, and certain comorbidities (diabetes, hypertension, osteoarthritis, and rheumatoid arthritis) and negatively with cardiovascular disease (CVD) and heart failure. Among those prescribed NSAIDs, AKI was associated with older age, greater deprivation, chronic kidney disease (CKD), CVD, heart failure, diabetes, and hypertension. CONCLUSION: Despite generally good prescribing practice, NSAID prescribing was identified in some people at higher risk of AKI (for example, patients with CKD and older) for whom medication review and NSAID deprescribing should be considered

The smectic order of wrinkles

A thin elastic sheet lying on a soft substrate develops wrinkled patterns when subject to an external forcing or as a result of geometric incompatibility. Thin sheet elasticity and substrate response equip such wrinkles with a global preferred wrinkle spacing length and with resistance to wrinkle curvature. These features are responsible for the liquid crystalline smectic-like behaviour of such systems at intermediate length scales. This insight allows better understanding of the wrinkling patterns seen in such systems, with which we explain pattern breaking into domains, the properties of domain walls and wrinkle undulation. We compare our predictions with numerical simulations and with experimental observations

Sex difference in the association of metabolic syndrome with high sensitivity C-reactive protein in a Taiwanese population

<p>Abstract</p> <p>Background</p> <p>Although sex differences have been reported for associations between components of metabolic syndrome and inflammation, the question of whether there is an effect modification by sex in the association between inflammation and metabolic syndrome has not been investigated in detail. Therefore, the aim of this study was to compare associations of high sensitivity C-creative protein (hs-CRP) with metabolic syndrome and its components between men and women.</p> <p>Methods</p> <p>A total of 1,305 subjects aged 40 years and over were recruited in 2004 in a metropolitan city in Taiwan. The biochemical indices, such as hs-CRP, fasting glucose levels, lipid profiles, urinary albumin, urinary creatinine and anthropometric indices, were measured. Metabolic syndrome was defined using the American Heart Association and the National Heart, lung and Blood Institute (AHA/NHLBI) definition. The relationship between metabolic syndrome and hs-CRP was examined using multivariate logistic regression analysis.</p> <p>Results</p> <p>After adjustment for age and lifestyle factors including smoking, and alcohol intake, elevated concentrations of hs-CRP showed a stronger association with metabolic syndrome in women (odds ratio comparing tertile extremes 4.80 [95% CI: 3.31-6.97]) than in men (2.30 [1.65-3.21]). The p value for the sex interaction was 0.002. All components were more strongly associated with metabolic syndrome in women than in men, and all sex interactions were significant except for hypertension.</p> <p>Conclusions</p> <p>Our data suggest that inflammatory processes may be of particular importance in the pathogenesis of metabolic syndrome in women.</p

The structure of IL2 bound to the three chains of the IL2 receptor and how signaling occurs

The interleukin-2 molecule and receptor were the first of the interleukins to be discovered and characterized at the molecular level. Now after 20 years of effort, two groups have succeeded in determining the structure of IL2 bound to the external domains of the three receptor chains in a quaternary complex. What do we know now that we did not know before this structural information was available, and how do these new data help us to develop new therapies