A cost utility analysis alongside a cluster-randomised trial evaluating a minor ailment service compared to usual care in community pharmacy.

BACKGROUND: Minor ailments are "self-limiting conditions which may be diagnosed and managed without a medical intervention". A cluster randomised controlled trial (cRCT) was designed to evaluate the clinical, humanistic and economic outcomes of a Minor Ailment Service (MAS) in community pharmacy (CP) compared with usual care (UC). METHODS: The cRCT was conducted for 6 months from December 2017. The pharmacist-patient intervention consisted of a standardised face-to-face consultation on a web-based program using co-developed protocols, pharmacists' training, practice change facilitators and patients' educational material. Patients requesting a non-prescription medication (direct product request) or presenting minor ailments received MAS or UC and were followed-up by telephone 10-days after the consultation. The primary economic outcomes were incremental cost-utility ratio (ICUR) of the service and health related quality of life (HRQoL). Total costs included health system, CPs and patient direct costs: health professionals' consultation time, medication costs, pharmacists' training costs, investment of the pharmacy and consultation costs within the 10 days following the initial consultation. The HRQoL was obtained using the EuroQoL 5D-5L at the time of the consultation and at 10-days follow up. A sensitivity analysis was carried out using bootstrapping. There were two sub-group analyses undertaken, for symptom presentation and direct product requests, to evaluate possible differences. RESULTS: A total of 808 patients (323 MAS and 485 UC) were recruited in 27 CPs with 42 pharmacists (20 MAS and 22 UC). 64.7% (n = 523) of patients responded to follow-up after their consultation in CP. MAS patients gained an additional 0.0003 QALYs (p = 0.053). When considering only MAS patients presenting with symptoms, the ICUR was 24,733€/QALY with a 47.4% probability of cost-effectiveness (willingness to pay of 25,000€/QALY). Although when considering patients presenting for a direct product request, MAS was the dominant strategy with a 93.69% probability of cost-effectiveness. CONCLUSIONS: Expanding community pharmacists' scope through MAS may benefit health systems. To be fully cost effective, MAS should not only include consultations arising from symptom presentation but also include an oversight of self-selected products by patients. MAS increase patient safety through the appropriate use of non-prescription medication and through the direct referral of patients to GP. TRIAL REGISTRATION: ISRCTN, ISRCTN17235323 . Registered 07/05/2021 - Retrospectively registered

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster.

Sequence variants in cis-acting enhancers are important for polygenic disease, but their role in Mendelian disease is poorly understood. Redundancy between enhancers that regulate the same gene is thought to mitigate the pathogenic impact of enhancer mutations. Recent findings, however, have shown that loss-of-function mutations in a single enhancer near PTF1A cause pancreas agenesis and neonatal diabetes. Using mouse and human genetic models, we show that this enhancer activates an entire PTF1A enhancer cluster in early pancreatic multipotent progenitors. This leading role, therefore, precludes functional redundancy. We further demonstrate that transient expression of PTF1A in multipotent progenitors sets in motion an epigenetic cascade that is required for duct and endocrine differentiation. These findings shed insights into the genome regulatory mechanisms that drive pancreas differentiation. Furthermore, they reveal an enhancer that acts as a regulatory master key and is thus vulnerable to pathogenic loss-of-function mutations

Graft Risk Index After Liver Transplant: Internal and External Validation of a New Spanish Indicator

OBJECTIVES: Scarcity of liver grafts has led to the use of marginal donors, consequently increasing the number of complications posttransplant. To prevent this situation, several indicators have been developed. However, important differences remain among countries. Here, we compared an early-risk liver transplant indicator based on the Spanish Liver Transplant Registry, called the Graft Risk Index, versus the US donor risk index and the Eurotransplant donor risk index. MATERIALS AND METHODS: The new indicator was based on prospectively collected data from 600 adult liver transplants performed in our center. We considered 2 events to compare the indexes: graft survival and rejection-free graft survival, with Cox proportional regression for analyses. Power to predict graft survival was evaluated by calculating the receiver operating characteristic area under the curve. RESULTS: We found no differences between the US and Eurotransplant donor risk indexes in prediction of patients with and without early graft failure. With regard to early survival, only the Graft Risk Index allowed better survival discrimination, in which survival progressively decreased with values = 3 (with probability of graft survival at 1 month of 68%; 95% confidence interval, 46.2-82.5). This increase in risk was significant compared with the standard group (hazard ratio of 10.15; 95% confidence interval, C 3.91- 26.32; P < .001). We calculated powers of prediction of 0.52 (95% confidence interval, 0.43-0.62), 0.54 (95% confidence interval, 0.45-0.65), and 0.69 (95% confidence interval, 0.61-0.77) for donor risk index, Eurotransplant donor risk index, and early Graft Risk Index, respectively. CONCLUSIONS: Neither the US donor risk index nor the Eurotransplant donor risk index was valid for our Spanish liver donation and transplant program. Therefore, an indicator to predict posttransplant graft survival that is adapted to our environment is necessary. This national Graft Risk Index can be a useful tool to optimize donor-recipient matchin

What fuels suboptimal care of peripheral intravenous catheter-related infections in hospitals? A qualitative study of decision-making among Spanish nurses

Availability of data and materials: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.Copyright . Background: Peripheral intravenous catheters (PIVC) are commonly used in hospital worldwide. However, PIVC are not exempt from complications. Catheter-related bloodstream infections (CRBSI) increase morbidity and mortality rates, and costs for the healthcare organization. PIVC care is shaped by the complex mix of professional and organizational culture, such as knowledge gaps, low perception of impact of PIVCs on patient safety, or lack of hospital guidelines. Aim: To explore determinants of decision-making about the prevention of PIVC-BSI among nurses in Spanish hospitals. Methods: We conducted a descriptive qualitative study with semi-structured interviews in three public hospitals, the Balearic Islands Health Care Service in Spain. We considered hospital ward nurses working routinely with inpatients at any of the three hospitals for enrolment in the study. We approached relevant informants to identify suitable participants who recruited other participants through a ‘snowball’ technique. Fourteen inpatient nurses from the hospital took part in this study between September and November 2018. We employed several triangulation strategies to underpin the methodological rigour of our analysis and conducted the member checking, showing the information and codes applied in the recording of the interviews to identify the coherence and any discrepancies of the discourse by participants. We used the COREQ checklist for this study. Findings: We identified four major themes in the analysis related to determinants of care: The fog of decision-making in PIVC; The taskification of PIVC care; PIVC care is accepted to be suboptimal, yet irrelevant; and chasms between perceived determinants of poor PIVC care and its solutions. Conclusion: The clinical management of PIVCs appear ambiguous, unclear, and fragmented, with no clear professional responsibility and no nurse leadership, causing a gap in preventing infections. Furthermore, the perception of low risk on PIVC care impact can cause a relevant lack of adherence to the best evidence and patient safety. Implementing facilitation strategies could improve the fidelity of the best available evidence regarding PIVC care and raise awareness among nurses of impact that excellence of care.The College of Nurses of the Balearic Islands under Grant Number PI2018/0286

Associations of Non-Alcoholic Beverages with Major Depressive Disorder History and Depressive Symptoms Clusters in a Sample of Overweight Adults

This is the final version. Available on open access from MDPI via the DOI in this recordBackground: Meta-analysis of observational studies concluded that soft drinks may increase the risk of depression, while high consumption of coffee and tea may reduce the risk. Objectives were to explore the associations between the consumption of soft drinks, coffee or tea and: (1) a history of major depressive disorder (MDD) and (2) the severity of depressive symptoms clusters (mood, cognitive and somatic/vegetative symptoms). Methods: Cross-sectional and longitudinal analysis based on baseline and 12-month-follow-up data collected from four countries participating in the European MooDFOOD prevention trial. In total, 941 overweight adults with subsyndromal depressive symptoms aged 18 to 75 years were analyzed. History of MDD, depressive symptoms and beverages intake were assessed. Results: Sugar-sweetened soft drinks were positively related to MDD history rates whereas soft drinks with non-nutritive sweeteners were inversely related for the high vs. low categories of intake. Longitudinal analysis showed no significant associations between beverages and mood, cognitive and somatic/vegetative clusters. Conclusion: Our findings point toward a relationship between soft drinks and past MDD diagnoses depending on how they are sweetened while we found no association with coffee and tea. No significant effects were found between any studied beverages and the depressive symptoms clusters in a sample of overweight adults.European Union FP7National Institute for Health Research (NIHR

Soft Drinks and Symptoms of Depression and Anxiety in Overweight Subjects: A Longitudinal Analysis of an European Cohort

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: The data presented in this study are available on request from the corresponding author.BACKGROUND: Studies about the association of carbonated/soft drinks, coffee, and tea with depression and anxiety are scarce and inconclusive and little is known about this association in European adults. Our aim was to examine the association between the consumption of these beverages and depressive and anxiety symptom severity. METHODS: A total of 941 European overweight adults (mean age, 46.8 years) with subsyndromal depression that participated in the MooDFOOD depression prevention randomized controlled trial (Clinical Trials.gov identifier: NCT2529423; date of the study: from 2014 to 2018) were analyzed. Depressive and anxiety symptom severity and beverage consumption were assessed using multilevel mixed-effects ordinal logistic regression models for each beverage consumption (carbonated/soft drink with sugar, carbonated/soft drink with non-nutritive sweeteners, coffee, and tea) with the three repeated measures of follow-up (baseline and 6 and 12 months). A case report form for participants' sociodemographic and clinical characteristics, the Food Frequency Questionnaire, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder 7-Item Scale, the MINI International Neuropsychiatric Interview 5.0, the Short Questionnaire to Assess Health-Enhancing Psychical Activity, and the Alcohol Use Disorders Identification Test were the research tools used. RESULTS: Daily consumption of carbonated/soft drinks with sugar was associated with a higher level of anxiety. Trends towards significance were found for associations between both daily consumption of carbonated/soft drinks with sugar and non-nutritive sweeteners and a higher level of depression. No relationship was found between coffee and tea consumption and the level of depression and anxiety. CONCLUSIONS: The high and regular consumption of carbonated/soft drink with sugar (amount of consumption: ≥1 unit (200 mL)/day) tended to be associated with higher level of anxiety in a multicountry sample of overweight subjects with subsyndromal depressive symptoms. It is important to point out that further research in this area is essential to provide valuable information about the intake patterns of non-alcoholic beverages and their relationship with affective disorders in the European adult population.European Union FP7National Institute for Health and Care Research (NIHR

Multimodal intervention for preventing peripheral intravenous catheter failure in adults (PREBACP): a multicentre, cluster-randomised, controlled trial

Availability of data and materials: The datasets generated during and/or analysed during the current study are available upon request from group investigation. The data are available beginning 3 months and ending 5 years following article publication for to investigators, whose proposed use of data will have been approved by an independent review committee identified for to realise an individual participant data meta-analysis. Proposals may be submitted up to 36 months following article publication to IB-M ([email protected]) and EC-S ([email protected]).The College of Nurses of the Balearic Islands under award number PI2017/0192

Effect of COMBinAtion therapy with remote ischemic conditioning and exenatide on the Myocardial Infarct size: a two-by-two factorial randomized trial (COMBAT-MI)

Remote ischemic conditioning (RIC) and the GLP-1 analog exenatide activate different cardioprotective pathways and may have additive effects on infarct size (IS). Here, we aimed to assess the efficacy of RIC as compared with sham procedure, and of exenatide, as compared with placebo, and the interaction between both, to reduce IS in humans. We designed a two-by-two factorial, randomized controlled, blinded, multicenter, clinical trial. Patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention (PPCI) within 6 h of symptoms were randomized to RIC or sham procedure and exenatide or matching placebo. The primary outcome was IS measured by late gadolinium enhancement in cardiac magnetic resonance performed 3–7 days after PPCI. The secondary outcomes were myocardial salvage index, transmurality index, left ventricular ejection fraction and relative microvascular obstruction volume. A total of 378 patients were randomly allocated, and after applying exclusion criteria, 222 patients were available for analysis. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. IS was similar between groups for the RIC (24 ± 11.8% in the RIC group vs 23.7 ± 10.9% in the sham group, P = 0.827) and the exenatide hypotheses (25.1 ± 11.5% in the exenatide group vs 22.5 ± 10.9% in the placebo group, P = 0.092). There were no effects with either RIC or exenatide on the secondary outcomes. Unexpected adverse events or side effects of RIC and exenatide were not observed. In conclusion, neither RIC nor exenatide, or its combination, were able to reduce IS in STEMI patients when administered as an adjunct to PPCI