Using behavioural insights to increase HIV self‐sampling kit returns: a randomized controlled text message trial to improve England's HIV self‐sampling service

Objectives

The aim of the study was to determine whether behaviourally informed short message service (SMS) primer and reminder messages could increase the return rate of HIV self‐sampling kits ordered online.

Methods

The study was a 2 × 2 factorial design randomized control trial. A total of 9585 individuals who ordered a self‐sampling kit from www.freetesting.hiv different SMS combinations: 1) standard reminders sent days 3 and 7 after dispatch (control); 2) primer sent 1 day after dispatch plus standard reminders; 3) behavioural insights (BI) reminders (no primer); or 4) primer plus BI reminders. The analysis was restricted to individuals who received all messages (n = 8999). We used logistic regression to investigate independent effects of the primer and BI reminders and their interaction. We explored the impact of sociodemographic characteristics on kit return as a secondary analysis.

Results

Those who received the primer and BI reminders had a return rate 4% higher than that of those who received the standard messages. We found strong evidence of a positive effect of the BI reminders (odds ratio 1.13; 95% confidence interval 1.04–1.23; P = 0.003) but no evidence for an effect of the primer, or for an interaction between the two interventions. Odds of kit return increased with age, with those aged ≥ 65 years being almost 2.5 times more likely to return the kit than those aged 25–34 years. Men who have sex with men were 1.5–4.5 times more likely to return the kit compared with other sexual behaviour and gender identity groups. Non‐African black clients were 25% less likely to return the kit compared with other ethnicities.

Conclusions

Adding BI to reminder messages was successful in improving return rates at no additional cost.     

影响压迫疗法一致性的因素

从业医师时常报道下肢溃疡病人坚持治疗非常困难,尽管对治疗难度有多大了解较少。本文介绍了从业医师如何提供关于下肢溃疡病人有效护理,讨论了压迫疗法的选择,如何影响一致性。评估和一致性从业者常发现处理如下问题较困难:病人不接受治疗方案、病情治疗困难和病人缺乏进步思想。促进一致性需要从业医师去养成一个与患者敏锐的医患关系,认识患者的问题。选择合适的疗法一篇关于压迫疗法综述的结论是:①在压迫治疗方面有较高的压力(35~45mmHg)优于低的压力(15~25 mmHg);②具有弹性和无弹性的多层绷带方法,优于单层方法,对特定的病人用最佳…     

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin receptor function, nomenclature and pharmacology

Orexin signaling is essential for normal regulation of arousal and behavioral state control and represents an attractive target for therapeutics combating insomnia. Alternatively termed hypocretins, these neuropeptides were named to reflect sequence similarity to incretins and their potential to promote feeding. Current nomenclature reflects these molecular and biochemical discovery approaches in which HCRT, HCRTR1, and HCRTR2 genes encode prepro-orexin, the orexin 1 receptor (OX(1)) and the orexin 2 receptor (OX(2))-gene names designated by the Human Genome Organization and receptor names designated by the International Union of Basic and Clinical Pharmacology. Orexinergic neurons are most active during wakefulness and fall silent during inactive periods, a prolonged disruption in signaling most profoundly resulting in hypersomnia and narcolepsy. Hcrtr2 mutations underlie the etiology of canine narcolepsy, deficiencies in orexin-producing neurons are observed in the human disorder, and ablation of mouse orexin neurons or the Hcrt gene results in a narcolepsy-cataplexy phenotype. The development of orexin receptor antagonists and genetic models targeting components of the orexin pathway have elucidated the OX(2) receptor-specific role in histamine-mediated arousal and the contribution of both receptors in brainstem pathways involved in vigilance state gating. Orexin receptor antagonists of varying specificity uncovered additional roles beyond sleep and feeding that include addiction, depression, anxiety, and potential influences on peripheral physiology. Combined genetic and pharmacological approaches indicate that orexin signaling may represent a confluence of sleep, feeding, and reward pathways. Selective orexin receptor antagonism takes advantage of these properties toward the development of novel insomnia therapeutics.     

Fructus Broussonetae extract improves cognitive function and endoplasmic reticulum stress in Alzheimer's disease models

This study investigated the effects and possible targets of Fructus Broussonetiae extract,a traditional Chinese medicinal herb,on a model of Alzheimer’s disease induced by beta-amyloid peptide 25-35 and D-galactose.The results revealed that intragastric administration of Fructus Broussonetiae significantly increased the expression of immunoglobulin-binding protein,a key factor in the endoplasmic reticulum stress-signaling pathway in rat hippocampus.In contrast,the treatment significantly decreased expression levels of PKR-like endoplasmic reticulum kinase and C/EBP homologous protein,and substantially improved learning,memory and spatial recognition dysfunction in rats.This evidence indicates that Fructus Broussonetiae extract improves spatial learning and memory abilities in rats by affecting the regulation of hippocampal endoplasmic reticulum stress and activation of the apoptosis pathway.     

Diagnostic significance of Wada procedure in very young children and children with developmental delay

Localization of vital components of neurological functioning has to be performed before epilepsy surgery can be considered in children with intractable epilepsy. This study reports the experience with the Wada procedure in very young children and/or developmentally delayed children with an a priori considerable chance of failing the procedure. The aim of this study was to indicate the applicability of this procedure in this patient group. The Wada procedure is described in 16 children under 10 years of age and/or have intelligence quotient scores below 50 and/or are critically ill and/or are behaviourally disturbed. Information on motor, language and memory functioning is obtained in respectively 13/15, 9/13, and 5/11 children. Nine children underwent epilepsy surgery without postoperative impairment of neurological functioning. In five children epilepsy surgery was not performed because of the results of the Wada procedure or the lack of information during the Wada procedure. One child became seizure-free before surgery. Even in very young, developmentally delayed or behaviourally disturbed children, the Wada test can provide important information with respect to the decision pro or contra epilepsy surgery.     

Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non-high-grade serous ovarian carcinomas

The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non-HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high-grade endometrioid (3/20; 15%), low-grade endometrioid (1/40; 2.5%), low-grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re-evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight ‘anomalous’ cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first ‘anomalous’ non-HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53-abnormal high-grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53-wildtype low-grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non-causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high-grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype-directed sequencing. Furthermore, in-depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2-related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.     

Clinical review: Practical recommendations on the management of perioperative heart failure in cardiac surgery

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.