Search

Background: Hip fractures are common fall-related injuries, with rehabilitation and recovery often complicated by cognitive impairment. Understanding what interventions exist, and in what settings, for people with hip fracture and co-occurring cognitive impairment is important in order to provide more evidence on rehabilitation and related outcomes for this population., Objective: To examine the extent, nature, and range of literature on rehabilitation interventions for adults with hip fracture and cognitive impairment., Methods: Articles were required to: include an adult population with hip fracture and cognitive impairment, include a rehabilitation intervention, and be published between January 1, 2000 and November 19, 2021. Articles were excluded if they were opinion pieces, study protocols, conference abstracts, or if they did not describe the rehabilitation intervention. Relevant articles were searched on the following electronic databases: MEDLINE, EMBASE, CINAHL Plus, APA PsycINFO, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database. All articles were double-screened by two reviewers and disagreements were resolved through consensus. Data were extracted and synthesized using descriptive approaches., Results: Seventeen articles were included in this scoping review. We identified a variety of interventions targeting this population; about half were specific to physical rehabilitation, with the other half incorporating components that addressed multiple aspects of the care journey. Interventions had varying outcomes and no studies qualitatively explored patient or family experiences. All intervations were initiated in hospital, with less than half including cross-sectoral components. About half of the articles described modifying or tailoring the intervention to the participants' needs, but there was limited information on how to adapt rehabilitation interventions for individuals with cognitive impairment., Conclusions: More work is need to better understand patient, family, and provider experiences with rehabilitation interventions, how to tailor interventions for those with cognitive impairment, and how to successfully implement sustainable interventions across sectors., Competing Interests: The authors have declared that no competing interests exist.

This study was designed to increase our understanding about characteristics and the impact of sensory symptoms (SS) and signs of hyperarousal (HA) in individuals with fragile X syndrome (FXS) from childhood through early adulthood and by gender. Data derived from the Fragile X Online Registry With Accessible Research Database (FORWARD), a natural history study of FXS, were analyzed using descriptive statistics and multivariate linear and logistic regression models to examine SS and signs of HA, their impact on behavioral regulation and limitations on the subject/family. The sample (N = 933) consisted of 720 males and 213 females. More males were affected with SS (87% vs. 68%) and signs of HA (92% vs. 79%). Subjects who were endorsed as having a strong sensory response had more comorbidities, including behavioral problems. The predominant SS was difficulty with eye gaze that increased with age in both genders. As individuals age, there was less use of non-medication therapies, such as occupational therapy (OT)/physical therapy (PT), but there was more use of psychopharmacological medications and investigational drugs for behaviors. Multiple regression models suggested that endorsing SS and signs of HA was associated with statistically significantly increased ABC-C-I subscale scores and limited participation in everyday activities. This study improves our understanding of SS and signs of HA as well as their impact in FXS. It supports the need for more research regarding these clinical symptoms, especially to understand how they contribute to well-known behavioral concerns.

Abstract Rheumatic joints have an altered cartilage turnover. Cartilage intermediate layer protein 1 (CILP-1) is secreted from articular chondrocytes and deposited into the cartilage extracellular matrix. We developed an immunoassay targeting a Matrix Metalloproteinase (MMP)-generated neo-epitope of CILP-1, named CILP-M. Human articular cartilage was cleaved with proteolytic enzymes and CILP-M levels were measured. We also quantified CILP-M in two studies from patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteoarthritis (OA) and explored the monitoring and prognostic potential of CILP-M in TNF-α inhibitory treatment and modified Stoke AS Spine Score (mSASSS) progression. CILP-M was generated by MMP-1, -8 and -12. In the discovery study, CILP-M was significantly higher in patients with RA, AS and OA than healthy donors (p 0.95 (p 0.90 (p

Background Due to the accumulation of information generated by the information society, it is necessary to establish scientific criteria for its systematization. The objective of the research was to understand the implicit theories on the use of bibliographic managers in the organization of scientific information in university teachers in Latin American university teachers (Colombia, Ecuador and Peru). Methods The interpretative paradigm, phenomenological method and qualitative approach were used. The key informants were defined by fifteen teachers with research experience. The technique was the semi-structured interview, and the instrument was the interview script. The study was based on four cyclical-recursive moments, the first was the natural attitude, where information was obtained from the key informants as a result of the interviews. The second moment allowed the epoche-eidetic reduction, consisting of the analysis of each interview. The third moment originated the transcendental epoche-reduction, analyzing each attribute and their consistency. The fourth moment revealed the constitution of the study, integrating in a semantic network the categories, subcategories, and attributes that emerged. Results Even when it is recognized from the cognitive conception about the concept of bibliographic managers, its applicability or use, it seems not to be so effective in scientific academic spaces and activities, because teachers are still anchored to the traditionalist vision of organizing information through “drive, folder or excel”, reflecting the resistance to change. Conclusions The imperative need for continuous training in the use of bibliographic managers in both students and teachers is asserted, reflected as a transversal strategy throughout all academic cycles and semesters and internalized as a research policy that leads to generate a new change in the conception of researching reliable scientific sources, optimizing time, organizing information and guaranteeing quality research.

Introduction Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose–response nature of any identified association, to inform future hypertension management.Methods and analysis The study will use data from 2 of Australia’s largest cohort studies; the Australian Longitudinal Study on Women’s Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004–2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used.Ethics and dissemination Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings.Trial registration number NCT05972785.

BackgroundChronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control. ObjectiveIn this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP and assess the feasibility of performance of a pilot study of adding lacosamide to opioid therapy in patients with CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in patients with painful CP. MethodsUsing the Bayesian optimal interval design, we will conduct a dose-escalation trial of adding lacosamide to opioid therapy in patients with painful CP enrolled in cohorts of size 3. The initial dose will be 50 mg taken orally twice a day, followed by incremental increases to a maximum dose of 400 mg/day, with lacosamide administered for 7 days at each dose level. Adverse events will be documented according to Common Terminology Criteria for Adverse Events (version 5.0). ResultsAs of December 2023, we have currently enrolled 6 participants. The minimum number of participants to be enrolled is 12 with a maximum of 24. We expect to publish the results by March 2025. ConclusionsThis trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of opioids in treating painful CP. It is anticipated that lacosamide will prove to be safe and well tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in patients with painful CP, and that lacosamide combined with opiates will lower the opioid dose necessary for pain relief and improve the safety profile of opioid use in treating painful CP. Trial RegistrationClinicaltrials.gov NCT05603702; https://clinicaltrials.gov/study/NCT05603702 International Registered Report Identifier (IRRID)PRR1-10.2196/50513

Abstract Background Within the Learning Health System (LHS) model, learning routines, including evaluation, allow for continuous incremental change to take place. Within these learning routines, evaluation assists in problem identification, data collection, and data transformation into contextualized information, which is then re-applied to the LHS environment. Evaluation that catalyzes learning and improvement may also contribute to health innovation sustainability. However, there is little consensus as to why certain evaluations seem to support learning and sustainability, while others impede it. This realist synthesis seeks to understand the contextual factors and underlying mechanisms or drivers that best support health systems learning and sustainable innovation. Methods This synthesis will be guided by Pawson and colleagues’ 2005 and Emmel and colleagues’ 2018 guidelines for conducting realist syntheses. The review process will encompass five steps: (1) scoping the review, (2) building theories, (3) identifying the evidence, (4) evidence selection and appraisal, and (5) data extraction and synthesis. An Expert Committee comprised of leaders in evaluation, innovation, sustainability, and realist methodology will guide this synthesis. Review findings will be reported using the RAMESES guidelines. Discussion The use of a realist review will allow for exploration and theorizing about the contextual factors and underlying mechanisms that make evaluations ‘work’ (or ‘not work’) to support learning and sustainability. Depending on results, we will attempt to synthesize findings into a series of recommendations for evaluations with the intention to support health systems learning and sustainability. Finalized results will be presented at national and international conferences, as well as disseminated via a peer-reviewed publication. Systematic review registration This realist synthesis protocol has been registered with PROSPERO ( https://www.crd.york.ac.uk/prospero/ ID 382690).

RationaleA common strategy to reduce COPD readmissions is to encourage patient follow-up with a physician within 1 to 2 weeks of discharge, yet evidence confirming its benefit is lacking. We used a new study design called target randomized trial emulation to determine the impact of follow-up visit timing on patient outcomes.MethodsAll Ontario residents aged 35 or older discharged from a COPD hospitalization were identified using health administrative data and randomly assigned to those who received and did not receive physician visit follow-up by within seven days. They were followed to all-cause emergency department visits, readmissions or death. Targeted randomized trial emulation was used to adjust for differences between the groups. COPD emergency department visits, readmissions or death was also considered.ResultsThere were 94,034 patients hospitalized with COPD, of whom 73.5% had a physician visit within 30 days of discharge. Adjusted hazard ratio for all-cause readmission, emergency department visits or death for people with a visit within seven days post discharge was 1.03 (95% Confidence Interval [CI]: 1.01-1.05) and remained around 1 for subsequent days; adjusted hazard ratio for the composite COPD events was 0.97 (95% CI 0.95-1.00) and remained significantly lower than 1 for subsequent days.ConclusionWhile a physician visit after discharge was found to reduce COPD events, a specific time period when a physician visit was most beneficial was not found. This suggests that follow-up visits should not occur at a predetermined time but be based on factors such as anticipated medical need.

ASPirin in Reducing Events in the Elderly (ASPREE), a placebo-controlled prevention trial of low dose aspirin, provided the opportunity to establish a biospecimen biobank from initially healthy persons aged 70+ years for future research. The ASPREE Healthy Ageing Biobank (ASPREE Biobank) collected, processed and stored blood and urine samples at -80degC or under nitrogen vapour at two timepoints, three years apart, from a willing subset of Australian ASPREE participants. Written informed consent included separate opt-in questions for biomarker and genetic testing. Fractionated blood and urine were aliquoted into multiple low-volume, barcoded cryotubes for frozen storage within 4 hours of collection. Specially designed and outfitted mobile laboratories provided opportunities for participation by people in regional and rural areas. Detailed, high quality demographic, physiological and clinical data were collected annually through the ASPREE trial. 12,219 participants contributed blood/urine at the first timepoint, 10,617 of these older adults provided 3-year follow-up samples, and an additional 1,712 provided saliva for DNA. The mean participant age was 74 years, 54% were female and 46% lived outside major cities. Despite geographical and logistical challenges, nearly 100% of blood/urine specimens were processed and frozen within 4 hours of collection into >1.4 million aliquots. After a median of 4.7 years, major clinical events among ASPREE Biobank participants included 332 with dementia, 613 with cardiovascular disease events, 1259 with cancer, 357 with major bleeds and 615 had died. The ASPREE Biobank houses and curates a large number of biospecimens collected prior to the clinical manifestations of major disease, and 3-year follow-up samples, all linked to high quality, extensive phenotypic information. This provides the opportunity to identify or validate diagnostic, prognostic and predictive biomarkers, and potentially study biological effectors, of ageing-related diseases or maintenance of older-age good health.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Abstract Rapid and efficient decontamination of the skin is a major task for emergency rescue services in the event of a chemical accident involving humans. While rinsing the skin with water (and soap) has been the standard procedure, some skepticism has developed in recent years regarding the situational suitability of this method. The efficacy of three different decontamination materials/techniques (Easyderm® cleaning cloth, water-soaked all-purpose sponge, rinsing with water) in removing Capsaicin, Bromadiolone, Paraquat and 2,2′-dichlorodiethylether (DCEE) from porcine skin was compared. Different cleaning motions (wiping, twisting, pressing) with the Easyderm® were evaluated for their effectiveness in removing Capsaicin from porcine skin. Finally, the impact of different exposure times of the skin to Capsaicin on the decontamination process were investigated. Contaminant recovery rates (CRRs) were analysed in the skin and in each decontamination material using high-performance-liquid-chromatography (HPLC; used for Capsaicin, Bromadiolone, Paraquat) or gas chromatography (GC; used for DCEE). Wiping the skin with the amphiphilic Easyderm® was most effective for decontamination of Capsaicin and DCEE, while the water rinsing method gave the best results for removing Paraquat and Bromadiolone. Both wiping with the Easyderm® and rotating the Easyderm® were significantly more effective in cleaning Capsaicin-contaminated skin than pressing the Easyderm® on the contamination area alone. Prolonged exposure times of the porcine skin to Capsaicin were associated with a decrease in efficacy of the following decontamination. Emergency rescue services should have materials available that can remove both hydrophilic and hydrophobic substances from skin. Since not all of our results for comparing different decontamination materials were as distinct as we expected, there are likely several other factors determining the efficacy of skin decontamination in some cases. Time is key; therefore, first responders should try to begin the decontamination process as soon as possible after arriving at the scene.

Objectives The pandemic and public health response to contain the virus had impacts on many aspects of young people’s lives including disruptions to daily routines, opportunities for social, academic, recreational engagement and early employment. Consequently, children, adolescents and young adults may have experienced mental health challenges that required use of mental health services. This study compared rates of use for inpatient and outpatient mental health services during the pandemic to pre-pandemic rates.Design Population-based repeated cross-sectional study.Setting Publicly delivered mental healthcare in primary and secondary settings within the province of Ontario, Canada.Participants All children 6–12 years of age (n=2 043 977), adolescents 13–17 years (n=1 708 754) and young adults 18–24 years (n=2 286 544), living in Ontario and eligible for provincial health insurance between March 2016 and November 2021.Primary outcome measures Outpatient mental health visits to family physicians and psychiatrists for: mood and anxiety disorders, alcohol and substance abuse disorders, other non-psychotic mental health disorders and social problems. Inpatient mental health visits to emergency departments and hospitalisations for: substance-related and addictive disorders, anxiety disorders, assault-related injuries, deliberate self-harm and eating disorders. All outcomes were analysed by cohort and sex.Results During the pandemic, observed outpatient visit rates were higher among young adults by 19.01% (95% CI: 15.56% to 22.37%; 209 vs 175 per 1000) and adolescent women 24.17% (95% CI: 18.93% to 29.15%; 131 vs 105 per 1000) for mood and anxiety disorders and remained higher than expected. Female adolescents had higher than expected usage of inpatient care for deliberate self-harm, eating disorders and assault-related injuries.Conclusions Study results raise concerns over prolonged high rates of mental health use during the pandemic, particularly in female adolescents and young women, and highlights the need to better monitor and identify mental health outcomes associated with COVID-19 containment measures and to develop policies to address these concerns.

Abstract In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics.

Abstract Distyly, a floral dimorphism associated with heteromorphic self-incompatibility and controlled by the S-locus supergene, evolved independently multiple times. Comparative analyses of the first transcriptome atlas for the main distyly model, Primula veris, with other distylous species produced the following findings. A set of 53 constitutively expressed genes in P. veris did not include any of the housekeeping genes commonly used to normalize gene expression in qPCR experiments. The S-locus gene CYP T acquired its role in controlling style elongation via a change in expression profile. Comparison of genes differentially expressed between floral morphs revealed that brassinosteroids and auxin are the main hormones controlling style elongation in P. veris and Fagopyrum esculentum, respectively. Furthermore, shared biochemical pathways might underlie the expression of distyly in the distantly related P. veris, F. esculentum and Turnera subulata, suggesting a degree of correspondence between evolutionary convergence at phenotypic and molecular levels. Finally, we provide the first evidence supporting the previously proposed hypothesis that distyly supergenes of distantly related species evolved via the recruitment of genes related to the phytochrome-interacting factor (PIF) signaling network. To conclude, this is the first study that discovered homologous genes involved in the control of distyly in distantly related taxa.

Key Clinical Message Acquired factor VIII inhibitors can be a rare cause of extensive intramuscular bleeding requiring fasciotomy. The subsequent postoperative period requires close monitoring due to high risk of fatal blood loss. Abstract Acquired factor VIII inhibitors are a rare cause of often extensive bleeding and subsequently large hematomas. This disorder's overall mortality can reach 38%, largely due to immunosuppression and subsequent infections or an underlying cause such as malignancy. The patient in this case study presented with a hematoma and extensive ecchymosis of the hand and forearm, which continued to progress, precipitating compartment syndrome of the hand and forearm and ultimately requiring fasciotomy. The combination of factors led to significant blood loss in the postoperative period requiring major fluid resuscitation and intensive care unit (ICU) level care. Due to this disorder's rarity and overall mortality, we present this case report with a literature review for management of acquired hemophilia in the setting of urgent fasciotomy.

Introducción: a pesar de que varias investigaciones han demostrado que el mindfulness o atención plena influye en el estrés percibido, se ha evidenciado la carencia de estudios que hayan probado las relaciones entre la regulación emocional, la atención plena y el estrés percibido, específicamente en el personal de la salud que labora en unidades de cuidados intensivos. Objetivo: probar la relación entre la atención plena y el estrés percibido en servidores de la salud de hospitales públicos y privados de Santo Domingo de los Colorados, Ecuador, para identificar si esta relación es mediada por la regulación emocional. Método: se realizó un estudio cuantitativo de alcance descriptivo correlacional y diseño transversal donde se aplicó un cuestionario conformado por 39 preguntas tomadas de tres escalas psicosomáticas a 382 servidores de la salud de unidades de cuidados intensivos de las instituciones antes mencionadas. Se midieron las variables: atención plena, regulación emocional y estrés percibido. Los análisis estadísticos fueron desarrollados a través de Excel y Statistical Package for Social Sciences 21. Resultados: los análisis estadísticos evidenciaron que la atención plena influyó en el estrés percibido (β=0,428**) y, también, en la regulación emocional (β=0,488**), así mismo la regulación emocional influyó sobre el estrés percibido (β=0,417**). Conclusiones: se corroboró que la regulación emocional tiene un efecto mediador entre el mindfulness o atención plena y el estrés percibido en los servidores de la salud de las unidades de cuidados intensivos. Este personal a menudo desarrolla actividades sin prestar atención plena, sin embargo, tienen control sobre sus actividades laborales y están en la capacidad de regular y ocultar emociones que se les pueda presentar dentro de los contextos laborales de la salud y, de esta manera, disminuir los riesgos de padecer estrés.

Introducción: la pandemia de COVID-19 inició en Wuhan, China, en el año 2019, trajo graves complicaciones tanto físicas como psicológicas y llegó a ocasionar hasta la muerte. Es importante realizar un estudio en los estudiantes de Enfermería de la Pontificia Universidad Católica del Ecuador, Sede Santo Domingo, sobre el manejo de esta enfermedad en cuanto a su perfil farmacológico. Objetivo: se pretende determinar la infradosificación de fármacos utilizados durante la pandemia de COVID-19 en alumnos de la Pontificia Universidad Católica de Santo Domingo a fin de tener una visión de los diferentes tratamientos farmacológicos. Métodos: se realizó un estudio transversal, de tipo descriptivo, en una población de estudio de 615 alumnos pertenecientes a la Escuela de Enfermería de la Pontificia Universidad Católica de Santo Domingo evaluados por medio de una encuesta digital mediante un muestreo estratificado. Resultados: se trabajó con una muestra de 238 alumnos, con la mayor participación del género femenino, entre 21 y 25 años de edad. Las pruebas de diagnósticos para comprobar el contagio fueron la reacción en cadena de la polimerasa y otras medidas adoptadas. Los participantes manifestaron síntomas como la pérdida del olfato (12,16%), fiebre (11,81%) y cansancio (11,70%). Los fármacos que consumieron con mayor frecuencia fueron el paracetamol (32,79%) y la azitromicina (15,78) administrados según la eficacia de la prescripción médica (69,79%). Conclusiones: los fármacos más empleados fueron el paracetamol y la azitromicina, no existió abuso en la toma de medicamentos cumpliendo en su mayoría las indicaciones del médico.

Abstract A high number of trauma patients are under the influence of alcohol. Since many of them need immediate surgical procedures, it is imperative to be aware of the interaction of alcohol with general anesthesia. To counter challenges that arise from clinical studies, we designed an animal experiment in which 48 adult Wistar rats either received 1 g · kg−1 ethanol, 2 g · kg−1 ethanol or placebo via intraperitoneal application. Subsequently, they were anesthetized with an individual concentration of sevoflurane. The minimum alveolar concentration (MAC) of the different groups was assessed using Dixon’s up-and-down design and isotonic regression methods. The bootstrap estimate of the MAC of sevoflurane in the placebo group was 2.24 vol% (95% CI 1.97–2.94 vol%). In the low dose ethanol group, the bootstrap estimate was 1.65 vol% (95% CI 1.40–1.98 vol%), and in the high dose ethanol group, it was 1.08 vol% (95% CI 0.73–1.42 vol%). We therefore report that intraperitoneal application of 1 g · kg−1 or 2 g · kg−1 ethanol both resulted in a significant reduction of the MAC of sevoflurane in adult Wistar rats: by 26.3% and 51.8% respectively as compared to placebo.

Objectives This study sought to understand how stakeholder engagement impacts outcomes when there is a change in public funding within community mental health settings.Design A realist synthesis approach was used to address the research question to fully understand the role of stakeholder engagement as a mechanism in achieving outcomes (system and service user) in the context of community mental health service reform. An iterative process was used to identify programme theories and context–mechanism–outcome configurations within the literature.Results Findings highlight that in the absence of stakeholder engagement, funding changes may lead to negative outcomes. When stakeholders were engaged in some form, funding changes were more often associated with positive outcomes. Stakeholder engagement is multifaceted and requires considerable time and investment to support achieving intended outcomes when funding changes are implemented.Conclusions To support successful transformation of community mental health programmes, it is important that stakeholders are meaningfully engaged during funding allocation changes. Stakeholder engagement may entail connecting around a shared purpose, individual participation and meaningful interactions and dialogue.

Objectives To determine whether a voluntary referral-based interprofessional team-based primary care programme reached its target population and to assess the representativeness of referring primary care physicians.Design Cross-sectional analysis of administrative health data.Setting Ontario, Canada.Intervention TeamCare provides access to Community Health Centre services for patients of non-team physicians with complex health and social needs.Participants All adult patients who participated in TeamCare between 1 April 2015 and 31 March 2017 (n=1148), and as comparators, all non-referred adult patients of the primary care providers who shared patients in TeamCare (n=546 989), and a 1% random sample of the adult Ontario population (n=117 753).Results TeamCare patients were more likely to live in lower income neighbourhoods with a higher degree of marginalisation relative to comparison groups. TeamCare patients had a higher mean number of diagnoses, higher prevalence of all chronic conditions and had more frequent encounters with the healthcare system in the year prior to participation.Conclusions TeamCare reached a target population and fills an important gap in the Ontario primary care landscape, serving a population of patients with complex needs that did not previously have access to interprofessional team-based care.Strengths and limitations This study used population-level administrative health data. Data constraints limited the ability to identify patients referred to the programme but did not receive services, and data could not capture all relevant patient characteristics.

Introduction: COVID-19 caused healthcare professional workers have faced the pandemic on the frontline at the risk of being infected with the virus. Despite the low mortality rate at present and the low presence of patients with COVID-19 in health care centers, the application of a fourth booster dose has generated different positions among several countries. Objective: to determine whether personnel considered being at high risk of vulnerability in the city of Santo Domingo de los Colorados, Ecuador, have favorable intentions for receiving the fourth booster dose of the COVID-19 vaccine. Method: a quantitative study of correlational scope and cross-sectional design was developed. A questionnaire consisting of 16 questions measured the following variables: risk of infection, perceived knowledge of the vaccine, confidence in the vaccine and intention to be vaccinated; this questionnaire was applied to 375 participants. Statistical analyses were developed using the microsoft Excel spreadsheed and Statistical Packagefor Social Sciences 21 (SPSS 21). Results: statistical analyses showed that the risk of infection (β=0.178**), perceived knowledge about the vaccine (β=0.218**) and confidence about the vaccine (β=0.192**) are significantly correlated with the intention to be fully vaccinated, thus showing the need for a fourth booster dose by vulnerable sectors. Conclusion: this is the first research that presents results regarding the intention to vaccinate vulnerable people and highlights the intention to access a fourth booster dose.

Este artigo busca refletir, cultural e eticamente, sobre os desafios atuais e futuros da incorporação de novas biotecnologias de diagnóstico e tratamento de câncer no Brasil, bem como seu impacto no acesso e no controle do câncer no país. Para tanto, esta pesquisa parte da problematização da literatura sobre o tema e dos resultados de um estudo, que realizou uma websurvey com especialistas médicos dos setores público e privado brasileiros, associados às dez sociedades oncológicas mais representativas do país, atuantes nas áreas da clínica, cirurgia, radioterapia, patologia e diagnóstico. A discussão do estudo desenvolve-se em torno de três eixos temáticos: conhecimento e expectativas sobre o advento das novas tecnologias para o diagnóstico e tratamento do câncer; considerações estruturais e éticas envolvidas no uso atual e futuro das novas tecnologias; e possíveis cenários associados ao uso e aplicação das novas tecnologias para o diagnóstico e tratamento do câncer. Foram suscitadas algumas questões: novos paradigmas tecnológicos beneficiarão todos os usuários do Sistema Único de Saúde (SUS) ou serão privilégios de poucos? Diminuirão as discrepâncias em termos de oferta de distribuição de serviços, de recursos tecnológicos e de acesso ao diagnóstico e tratamento do câncer? Como diversos segmentos da sociedade poderão participar e influir nesse processo? Que tipos de cenários poderão ainda compor esse quadro? Visando contribuir com o planejamento da atenção ao câncer no Brasil, o artigo finaliza propondo o desenvolvimento de futuras ações a partir de cinco dimensões estratégicas: dimensão econômica; dimensão científica, de inovação e tecnológica; dimensão estrutural; dimensão cultural; e dimensão reguladora.

Introduction: COVID-19 vaccines stimulate immune processes that allow SARS-CoV-2, which affected a large part of the population, to be mitigated. The research on the adverse reactions presented by the COVID-19 vaccines must be continuous, since at present there is not enough information on their consequences. Objective: to determine the possible adverse reactions in young and older adults belonging to the Recinto Umpechico, inoculated against SARS-CoV-2 in Santo Domingo, during 2021. Method: a descriptive study was carried out in a population of 600 residents of said locality, inoculated against SARS-CoV-2. Non-probability convenience sampling was used, with a sample of 235 inhabitants. The study variables were: adverse reactions to COVID-19 vaccines, name of the vaccine received, number of doses, intensity and duration of symptoms, medications used to mitigate said adverse reactions. Results: 31.5% of the respondents who presented symptoms were male. The most common vaccine was Pfizer with 47.65%, with a percentage of symptoms of 29.36%. The most common adverse reaction was arm pain with 31.98%, lasting two to three days, equivalent to 48.96%; 62.65% used paracetamol and 20.5% used cold water baths to reduce symptoms. Conclusions: the vaccines manufactured by the different pharmaceutical companies cause adverse reactions that range from mild to severe, manifesting at any age and for a short or long term, which in most cases are easily treated with pharmacological and non-pharmacological medications.

Objective Patient and family engagement (PE) in health service planning and improvement is widely advocated, yet little prior research offered guidance on how to optimise PE, particularly in hospitals. This study aimed to engage stakeholders in generating evidence-informed consensus on recommendations to optimise PE.Design We transformed PE processes and resources from prior research into recommendations that populated an online Delphi survey.Setting and participants Panellists included 58 persons with PE experience including: 22 patient/family advisors and 36 others (PE managers, clinicians, executives and researchers) in round 1 (100%) and 55 in round 2 (95%).Outcome measures Ratings of importance on a seven-point Likert scale of 48 strategies organised in domains: engagement approaches, strategies to integrate diverse perspectives, facilitators, strategies to champion engagement and hospital capacity for engagement.Results Of 50 recommendations, 80% or more of panellists prioritised 32 recommendations (27 in round 1, 5 in round 2) across 5 domains: 5 engagement approaches, 4 strategies to identify and integrate diverse patient/family advisor perspectives, 9 strategies to enable meaningful engagement, 9 strategies by which hospitals can champion PE and 5 elements of hospital capacity considered essential for supporting PE. There was high congruence in rating between patient/family advisors and healthcare professionals for all but six recommendations that were highly rated by patient/family advisors but not by others: capturing diverse perspectives, including a critical volume of advisors on committees/teams, prospectively monitoring PE, advocating for government funding of PE, including PE in healthcare worker job descriptions and sharing PE strategies across hospitals.Conclusions Decision-makers (eg, health system policy-makers, hospitals executives and managers) can use these recommendations as a framework by which to plan and operationalise PE, or evaluate and improve PE in their own settings. Ongoing research is needed to monitor the uptake and impact of these recommendations on PE policy and practice.

Wastewater-based epidemiology is a well-established tool for detecting and monitoring the spread of enteric pathogens and the use of illegal drugs in communities in real time. Since only a few studies in Italy have investigated the correlation between SARS-CoV-2 in wastewater and the prevalence of COVID-19 cases from clinical testing, we conducted a one-year wastewater surveillance study in Sicily to correlate the load of SARS-CoV-2 RNA in wastewater and the reported cumulative prevalence of COVID-19 in 14 cities from October 2021 to September 2022. Furthermore, we investigated the role of SARS-CoV-2 variants and subvariants in the increase in the number of SARS-CoV-2 infections. Our findings showed a significant correlation between SARS-CoV-2 RNA load in wastewater and the number of active cases reported by syndromic surveillance in the population. Moreover, the correlation between SARS-CoV-2 in wastewater and the active cases remained high when a lag of 7 or 14 days was considered. Finally, we attributed the epidemic waves observed to the rapid emergence of the Omicron variant and the BA.4 and BA.5 subvariants. We confirmed the effectiveness of wastewater monitoring as a powerful epidemiological proxy for viral variant spread and an efficient complementary method for surveillance.

Introduction Long-term safety and efficacy of upadacitinib in patients with active ankylosing spondylitis (AS) has not been previously reported.Methods In SELECT-AXIS 1, patients receiving placebo were switched to upadacitinib 15 mg once daily at week 14 while patients initially randomised to upadacitinib continued their regimen through week 104. Efficacy was assessed using as-observed (AO) and non-responder imputation (NRI).Results Of 187 patients randomised, 144 patients (77%) completed week 104. Among patients receiving continuous upadacitinib, 85.9% (AO) and 65.6% (NRI) achieved Assessment of SpondyloArthritis international Society 40 response (ASAS40) at week 104. Similar magnitude of ASAS40 responses were observed among patients who switched from placebo to upadacitinib (88.7% and 63.8%, respectively). The mean change from baseline to week 104 in Spondyloarthritis Research Consortium of Canada MRI spine and sacroiliac joint inflammation scores were –7.3 and –5.3, respectively, in the continuous upadacitinib group and –7.9 and –4.9 in the placebo-to-upadacitinib switch group. The mean (95% CI) change from baseline to week 104 in the modified Stoke Ankylosing Spondylitis Spine Score was 0.7 (0.3, 1.1) in the total group. Adverse event rate was 242.7/100 patient-years. No serious infections, adjudicated major adverse cardiovascular events, lymphoma, non-melanoma skin cancer, or gastrointestinal perforations were observed.Conclusions Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 2 years for ASAS40 and other clinically relevant endpoints. A low rate of radiographic progression was observed and no new safety findings were observed.

La esteatosis no alcohólica es asociada con pronóstico benigno. Sin embargo, puede progresar a fibrosis, aunque no se comprende completamente el comportamiento de los genes que contribuyen a esta progresión. El objetivo de esta investigación fue analizar los indicios tempranos de fibrogénesis en la esteatosis no alcohólica en pacientes obesos frente a no obesos. Se realizó un estudio descriptivo prospectivo que incluyó a pacientes con esteatosis no alcohólica. Estos fueron divididos en dos grupos: obesos y no obesos. Se obtuvo información sociodemográfica, antropométrica y de padecimientos de componentes del síndrome metabólico. Se determinaron parámetros bioquímicos y niveles de expresión de los genes TNF-α, NF-kβ, CYP2E1, TGF-β, OPN, COL4α5 y HGF por RT-PCR. Los resultados muestran diferencias significativas en los niveles de expresión del gen CYP2E1, siendo mayor en pacientes obesos que padecían síndrome metabólico completo. Además, en pacientes no obesos sin componentes del síndrome metabólico se activa TGF-β como participante de vías fibrogénicas, y en pacientes obesos con síndrome metabólico completo el nivel de expresión significativo de CYP2E1 podría indicar una señal de alarma por un posible progreso de la enfermedad. Debe prestarse especial atención y seguimiento de la esteatosis en pacientes obesos.

Introduction: the use of Information and Communications Technology (ICT) is an indispensable tool for the continuous distance teaching-learning process. Technostress is the result of the individual inability of a person to adapt normally to the use of new technologies within their work activities. Objective: to identify the stress factors associated with the use of ICT in primary and secondary education teachers in the context of the COVID-19 pandemic (November 2021 and January 2022), in Santo Domingo de los Colorados, Ecuador. There was implemented the complete closure of schools as a sanitary measure. Method: a study of quantitative approach of correlational scope and transactional design, applied to 485 teachers of fiscal and private educational units, to whom a questionnaire of 20 questions was applied, that measured different factors, such as: skepticism about the use of ICT, work fatigue, anxiety and inefficiency. The results of the study were statistically analyzed through Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA) and Structural Equation Modeling (SEM); developed in SPPS 20 and AMOS 24. Results: through the estimates thrown in the AMOS Output, we obtained: skepticism (β=0.327), work fatigue (β=0.238), anxiety (β=0.394) and inefficiency (β=0.010). Conclusions: it was possible to show that skepticism, work fatigue and anxiety are influential factors in the presence of teaching technostress, while inefficiency is not. These aspects will serve as a basis for the formulation of strategies and measures that allow the effective and sustainable integration of ICTs in the educational field.

Pygmy Chameleons of the genus Rhampholeon represent a moderately diverse, geographically circumscribed radiation, with most species (18 out of 19 extant taxa) limited to East Africa. The one exception is Rhampholeon spectrum, a species restricted to West-Central African rainforests. We set out to characterize the geographic basis of genetic variation in this disjunctly distributed Rhampholeon species using a combination of multilocus Sanger data and genomic sequences to explore population structure and range-wide phylogeographic patterns. We also employed demographic analyses and niche modeling to distinguish between alternate explanations to contextualize the impact of past geological and climatic events on the present-day distribution of intraspecific genetic variation. Phylogenetic analyses suggest that R. spectrum is a complex of five geographically delimited populations grouped into two major clades (montane vs. lowland). We found pronounced population structure suggesting that divergence and, potentially, speciation began between the late Miocene and the Pleistocene. Sea level changes during the Pleistocene climatic oscillations resulted in allopatric divergence associated with dispersal over an ocean channel barrier and colonization of Bioko Island. Demographic inferences and range stability mapping each support diversification models with secondary contact due to population contraction in lowland and montane refugia during the interglacial period. Allopatric divergence, congruent with isolation caused by geologic uplift of the East African rift system, the "descent into the Icehouse," and aridification of sub-Saharan Africa during the Eocene-Oligocene are identified as the key events explaining the population divergence between R. spectrum and its closely related sister clade from the Eastern Arc Mountains. Our results unveil cryptic genetic diversity in R. spectrum, suggesting the possibility of a species complex distributed across the Lower Guinean Forest and the Island of Bioko. We highlight the major element of species diversification that modelled today's diversity and distributions in most West-Central African vertebrates.

BackgroundMultiple conditions are more prevalent in some minoritised ethnic groups and are associated with higher mortality rate but studies examining differential mortality once conditions are established is US-based. Our study tested whether the association between multiple conditions and mortality varies across ethnic groups in England.Methods and findingsA random sample of primary care patients from Clinical Practice Research Datalink (CPRD) was followed from 1st January 2015 until 31st December 2019. Ethnicity, usually self-ascribed, was obtained from primary care records if present or from hospital records. Long-term conditions were counted from a list of 32 that have previously been associated with greater primary care, hospital admissions, or mortality risk. Cox regression models were used to estimate mortality by count of conditions, ethnicity and their interaction, with adjustment for age and sex for 532,059 patients with complete data. During five years of follow-up, 5.9% of patients died. Each additional condition at baseline was associated with increased mortality. The direction of the interaction of number of conditions with ethnicity showed a statistically higher mortality rate associated with long-term conditions in Pakistani, Black African, Black Caribbean and Other Black ethnic groups. In ethnicity-stratified models, the mortality rate per additional condition at age 50 was 1.33 (95% CI 1.31,1.35) for White ethnicity, 1.43 (95% CI 1.26,1.61) for Black Caribbean ethnicity and 1.78 (95% CI 1.41,2.24) for Other Black ethnicity.ConclusionsThe higher mortality rate associated with having multiple conditions is greater in minoritised compared with White ethnic groups. Research is now needed to identify factors that contribute to these inequalities. Within the health care setting, there may be opportunities to target clinical and self-management support for people with multiple conditions from minoritised ethnic groups.

BackgroundHip fractures are common fall-related injuries, with rehabilitation and recovery often complicated by cognitive impairment. Understanding what interventions exist, and in what settings, for people with hip fracture and co-occurring cognitive impairment is important in order to provide more evidence on rehabilitation and related outcomes for this population.ObjectiveTo examine the extent, nature, and range of literature on rehabilitation interventions for adults with hip fracture and cognitive impairment.MethodsArticles were required to: include an adult population with hip fracture and cognitive impairment, include a rehabilitation intervention, and be published between January 1, 2000 and November 19, 2021. Articles were excluded if they were opinion pieces, study protocols, conference abstracts, or if they did not describe the rehabilitation intervention. Relevant articles were searched on the following electronic databases: MEDLINE, EMBASE, CINAHL Plus, APA PsycINFO, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database. All articles were double-screened by two reviewers and disagreements were resolved through consensus. Data were extracted and synthesized using descriptive approaches.ResultsSeventeen articles were included in this scoping review. We identified a variety of interventions targeting this population; about half were specific to physical rehabilitation, with the other half incorporating components that addressed multiple aspects of the care journey. Interventions had varying outcomes and no studies qualitatively explored patient or family experiences. All intervations were initiated in hospital, with less than half including cross-sectoral components. About half of the articles described modifying or tailoring the intervention to the participants' needs, but there was limited information on how to adapt rehabilitation interventions for individuals with cognitive impairment.ConclusionsMore work is need to better understand patient, family, and provider experiences with rehabilitation interventions, how to tailor interventions for those with cognitive impairment, and how to successfully implement sustainable interventions across sectors.

Interindividual anatomical differences in the human cortex can lead to suboptimal current directions and may result in response variability of transcranial electrical stimulation methods. These differences in brain anatomy require individualized electrode stimulation montages to induce an optimal current density in the targeted area of each individual subject. We aimed to explore the possible modulatory effects of 140 Hz transcranial alternating current stimulation (tACS) on the somatosensory cortex using personalized multi-electrode stimulation montages. In two randomized experiments using either tactile finger or median nerve stimulation, we measured by evoked potentials the plasticity aftereffects and oscillatory power changes after 140 Hz tACS at 1.0 mA as compared to sham stimulation (n = 17, male = 9). We found a decrease in the power of oscillatory mu-rhythms during and immediately after tactile discrimination tasks, indicating an engagement of the somatosensory system during stimulus encoding. On a group level both the oscillatory power and the evoked potential amplitudes were not modulated by tACS neither after tactile finger stimulation nor after median nerve stimulation as compared to sham stimulation. On an individual level we could however demonstrate that lower angular difference (i.e., differences between the injected current vector in the target region and the source orientation vector) is associated with significantly higher changes in both P20/N20 and N30/P30 source activities. Our findings suggest that the higher the directionality of the injected current correlates to the dipole orientation the greater the tACS-induced aftereffects are.

Introduction: the quality of medical care is directly related to the appropriate work environment and the satisfaction of the health staff. With the appearance of COVID-19, the work environment in health institutions has worsened. Objective: to identify the factors that influence the work environment of the public and private health institutions of Santo Domingo de los Tsáchilas, Ecuador, during the period June-August 2021. Method: implementation of a study with a quantitative approach of correlational scope and transectional design in 349 health workers, to whom a 25-questions questionnaire was applied, that measured factors such as: contagion risk, working hours, medical resources and job stability. The results of the study were statistically analyzed through SPPS 20 and AMOS 24, with the previous development of Cronbach's alpha. Results: 94% of the participants considered the work environment of their institutions as inappropriate, while 6% said they did not. Females, and ages ranging between 22-35 years predominated. All the variables of the hypothesized model exceeded 0.70 and the total Cronbach's alpha reached 0.728; the hypothesized model met the convergent and discriminant validity of the variables. The risk of contagion yielded a value of β=0.148, while the working day resulted with β=0.010, medical resources β=0.006 and job stability β=0.007. Conclusions: the findings determined that the risk of contagion is the most influential factor in the work environment of the institutions under study during the beginning of the COVID-19 pandemic.

La recertificación es el resultado de un acto por el que una entidad legalmente acreditada, asegura que el profesional médico (previamente certificado) mantiene actualizados sus conocimientos y destrezas, y que ha desarrollado su actividad dentro del marco ético y científico adecuado al progreso del “saber” y del “hacer” propio de su especialidad. A pesar de un largo camino recorrido, en Uruguay no se ha podido establecer un proceso de recertificación universal. Múltiples actores (usuarios del sistema, médicos, Facultad de Medicina, programas de Desarrollo Profesional Médico Continuo) consideran que es una necesidad, sin embargo es necesario vencer algunas barreras para que se establezca un programa de recertificación. Se recorren algunos de estos aspectos en este documento, desarrollados en el contexto de un grupo de trabajo para el Congreso por los 100 años del Sindicato Médico del Uruguay.

Introduction: exclusive breastfeeding provides macro and micronutrients that are sufficient for the correct development and growth of the infant. The promotion of exclusive breastfeeding should be optimal, since early weaning has greatly increased nowadays. Objective: to determine what factors influence early weaning in mothers with infants from 0 to 11 months at the Augusto Egas Health Center, in the city of Santo Domingo, Ecuador. Method: a descriptive correlational study was undertaken, with a quantitative approach, during the period from July to the beginning of August 2021, in a population of 252 mothers who attended this health unit. A convenience sampling was carried out, and a sample of 153 mothers was obtained. The variables measured were: difficulties at the beginning of breastfeeding, foods that supplemented exclusive breastfeeding, early abandonment, myths that influenced the partial or complete abandonment of exclusive breastfeeding, and mothers who received information after delivery. Results: 85% of the mothers reported difficulties in the sufficient quantity of milk. Mothers did not abandon breastfeeding by their own decision, 64.7% expressed not believing in the myths. There was a majority of agreement in having received correct information after delivery from health personnel (64.7%). Conclusion: the insufficient amount of milk in mothers is the factor that influences the most in this health unit, so they opted for a mixed diet.

Durante el invierno las infecciones respiratorias agudas bajas (IRAB) determinan un incremento en la demanda asistencial, afectando sobre todo a los niños más pequeños. El objetivo de la investigación fue describir las características clínicas, modalidades de tratamiento y evolución de los menores de 2 años hospitalizados en el Hospital Pediátrico-Centro Hospitalario Pereira Rossell por IRAB de etiología viral durante el invierno de 2014. Se realizó un estudio descriptivo, retrospectivo, describiendo las características de los menores de 2 años hospitalizados del 9/6 al 21/9/2014 por IRAB de probable etiología viral. Se describieron las características epidemiológicas y clínicas, el tratamiento realizado y la evolución de los pacientes. En el período evaluado egresaron 742 niños (34% de los egresos de la institución). Tenían una mediana de edad de 4 meses; 18% presentaba al menos un factor de riesgo de IRAB grave. Se identifi có al virus respiratorio sincicial en 59,6%. La estadía hospitalaria tuvo una mediana de 4 días. En las salas de cuidados moderados se aplicó ventilación no invasiva a 46 niños, y oxigenación de alto fl ujo a 129 niños, logrando una mejoría clínica en el 87,0% y el 87,6% respectivamente. Ingresaron a unidades de cuidados intensivos 217 niños, 54% requirió asistencia ventilatoria mecánica. Dos pacientes fallecieron. En el período evaluado los niños pequeños con IRAB representaron una importante proporción de los egresos, con importante carga asistencial. La mayoría eran niños sin factores de riesgo. La aplicación de las técnicas de tratamiento en cuidados moderados fue efectiva, permitiendo disminuir la demanda de camas de cuidados intensivos.

Introduction The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients’ own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions.Methods and analysis International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm).Ethics and dissemination This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator’s site by the Ethics Committee ‘Ethikkommission Nordwest- und Zentralschweiz‘ (2020–00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles.Trial registration number NCT04293146.

Objectives Transcatheter aortic valve implantation (TAVI) is performed in elderly patients with severe aortic valve stenosis and increased operative risks. We tested the hypothesis that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have a predictive value for prevalent complications after TAVI and could serve as indicators of systemic inflammation in the early postoperative period.Design Prospective observational study.Setting This study is a secondary analysis of multicentre CESARO- study.Participants 48 patients with TAVI were included and 43 obtained the complete assessment.Primary and secondary outcome measures Patients’ clinical parameters, demographic data, peripheral AChE and BChE activities and routine blood markers were assessed throughout the perioperative period using bedside point-of-care measurements for AChE and BChE. Postoperative complication screening was conducted up to the third postoperative day and included infections, delirium and heart-rhythm disturbances. After assessment, the patients were divided into complication and noncomplication group.Results Of 43 patients, 24 developed postsurgical complications (55.8%). Preoperative assessment showed no significant differences regarding demographic data and laboratory markers, but preoperative BChE levels were significantly lower in patients who developed postoperative complications (complication group 2589.2±556.4 vs noncomplication group 3295.7±628.0, Cohen’s r=0.514, p

Introducción: en Uruguay se ofrece gratuitamente una vacuna tetravalente contra el virus del papiloma humano (VPH) a todas las adolescentes de 12 años o mayores. Las coberturas logradas no han sido las esperadas. Objetivo: describir el estado vacunal contra el VPH, motivos de no vacunación y reporte de efectos adversos en las adolescentes hospitalizadas en un centro de referencia en Uruguay. Material y método: estudio descriptivo mediante encuesta anónima a adolescentes de 12 años o mayores hospitalizadas en cuidados moderados del Hospital Pediátrico del Centro Hospitalario Pereira Rossell durante el segundo semestre de 2016. Se excluyeron las adolescentes que se negaron a participar, las portadoras de retardo mental o pasibles de cuidados paliativos. Se analizó: edad, estado vacunal contra VPH, motivos de no vacunación y de rechazo a la vacuna, efectos adversos. Fue aprobado por el Comité de Ética de la institución. Resultados: se encuestaron 112 adolescentes. Edad media: 13,5 años (12-14,6). Reportaron recibir al menos una dosis de la vacuna contra VPH: 45/112 (40,1%). Motivo de no vacunación más frecuente reportado: desconocimiento de la existencia de la vacuna: 48/67 (71,6%), seguido de rechazo o negativa de la adolescente o adulto responsable: 13/67 (19,4%). El principal motivo de rechazo a recibir la vacuna fue la falta de información: 7/13. No se registraron efectos adversos graves. Conclusiones: se observó una cobertura vacunal similar a datos nacionales. El conocimiento y la información de las adolescentes y sus cuidadores sobre esta vacuna fueron los principales motivos de no vacunación detectados.

Introduction International guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysis NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and dissemination The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration number NCT03573739.

Objective To identify the relationships between the context in which integrated care programmes (ICPs) for community-dwelling frail older people are applied, the mechanisms by which the programmes do (not) work and the outcomes resulting from this interaction by establishing a programme theory.Design Rapid realist review.Inclusion criteria Reviews and meta-analyses (January 2013–January 2019) and non-peer-reviewed literature (January 2013–December 2019) reporting on integrated care for community-dwelling frail older people (≥60 years).Analysis Selection and appraisal of documents was based on relevance and rigour according to the Realist And Meta-narrative Evidence Syntheses: Evolving Standards criteria. Data on context, mechanisms, programme activities and outcomes were extracted. Factors were categorised into the five strategies of the WHO framework of integrated people-centred health services (IPCHS).Results 27 papers were included. The following programme theory was developed: it is essential to establish multidisciplinary teams of competent healthcare providers (HCPs) providing person-centred care, closely working together and communicating effectively with other stakeholders. Older people and informal caregivers should be involved in the care process. Financial support, efficient use of information technology and organisational alignment are also essential. ICPs demonstrate positive effects on the functionality of older people, satisfaction of older people, informal caregivers and HCPs, and a delayed placement in a nursing home. Heterogeneous effects were found for hospital-related outcomes, quality of life, healthcare costs and use of healthcare services. The two most prevalent WHO-IPCHS strategies as part of ICPs are ‘creating an enabling environment’, followed by ‘strengthening governance and accountability’.Conclusion Currently, most ICPs do not address all WHO-IPCHS strategies. In order to optimise ICPs for frail older people the interaction between context items, mechanisms, programme activities and the outcomes should be taken into account from different perspectives (system, organisation, service delivery, HCP and patient).

Cough is induced by inhaled prostacyclin analogues including treprostinil (TRE), and, at higher doses, treprostinil palmitil (TP), a prodrug of TRE. In this report, we have investigated mechanisms involved in TRE- and TP-induced cough, using a dry powder formulation of TP (TPIP) to supplement previous data obtained with an aqueous suspension formulation of TP (TPIS). Experiments in guinea pigs and rats investigated the prostanoid receptor subtype producing cough and whether it involved activation of sensory nerves in the airways and vasculature. Experiments involved treatment with prostanoid, tachykinin and bradykinin receptor antagonists, a cyclooxygenase inhibitor and TRE administration to the isolated larynx or intravenously. In guinea pigs, cough with inhaled TRE (1.23 µg·kg−1) was not observed with an equivalent dose of TPIP and required higher inhaled doses (12.8 and 35.8 µg·kg−1) to induce cough. TRE cough was blocked with IP and tachykinin NK1 receptor antagonists but not with EP1, EP2, EP3, DP1 or bradykinin B2 antagonists or a cyclooxygenase inhibitor. TRE administered to the isolated larynx or intravenously in rats produced no apnoea or swallowing, whereas citric acid, capsaicin and hypertonic saline had significant effects. The mechanisms inducing cough with inhaled TRE likely involves the activation of prostanoid IP receptors on jugular C-fibres in the tracheobronchial airways. Cough induced by inhaled dry powder and nebulised formulations of TP occurs at higher inhaled doses than TRE, presumably due to the slow, sustained release of TRE from the prodrug resulting in lower concentrations of TRE at the airway sensory nerves.

BackgroundContinuity of care is a well-recognized principle of the primary care discipline owing to its medical, interpersonal, and cost-saving benefits. Relationship continuity or the ongoing therapeutic relationship between a patient and their physician is a particularly desirable goal, but its role in preventing the accumulation of chronic conditions diagnoses in individuals is unknown. The objective of this study was to investigate the effect of continuity of care with physicians on the rate of incident multimorbidity diagnoses in patients with existing conditions.MethodsThis was a population-based, retrospective cohort study from 2001 to 2015 that focused on patients aged 18 to 105 years with at least one chronic condition (n = 166,665). Our primary exposure was relationship continuity of care with general practitioners and specialists measured using the Bice-Boxerman Continuity of Care Index (COCI). COCI was specified as a time-dependent exposure prior to the observation period. Our outcomes of interest were the time to diagnosis of a second, third, and fourth chronic condition estimated using cause-specific hazard regressions accounting for death as a competing risk.FindingsWe observed that patients with a single chronic condition and high continuity of care (>0.50) were diagnosed with a second chronic condition or multimorbidity at an 8% lower rate compared to individuals with low continuity (cause-specific hazard ratio (HR) 0.92 (95% Confidence Interval 0.90-0.93; pConclusionsContinuity of care is a potentially modifiable health system factor that reduces the rate at which diagnoses of chronic conditions are made over time in patients with multimorbidity. Additional research is needed to explain the underlying mechanisms through which continuity is related to a protective effect and the clinical sequalae.

BackgroundMultimorbidity is increasing among older adults, but the impact of these recent trends on the extent and complexity of polypharmacy and possible variation by sex remains unknown. We examined sex differences in multimorbidity, polypharmacy (5+ medications) and hyper-polypharmacy (10+ medications) in 2003 vs 2016, and the interactive associations between age, multimorbidity level, and time on polypharmacy measures.Methods and findingsWe employed a repeated cross-sectional study design with linked health administrative databases for all persons aged ≥66 years eligible for health insurance in Ontario, Canada at the two index dates. Descriptive analyses and multivariable logistic regression models were conducted; models included interaction terms between age, multimorbidity level, and time period to estimate polypharmacy and hyper-polypharmacy probabilities, risk differences and risk ratios for 2016 vs 2003. Multimorbidity, polypharmacy and hyper-polypharmacy increased significantly over the 13 years. At both index dates prevalence estimates for all three were higher in women, but a greater absolute increase in polypharmacy over time was observed in men (6.6% [from 55.7% to 62.3%] vs 0.9% [64.2%-65.1%] for women) though absolute increases in multimorbidity were similar for men and women (6.9% [72.5%-79.4%] vs 6.2% [75.9%-82.1%], respectively). Model findings showed that polypharmacy decreased over time among women aged < 90 years (especially for younger ages and those with fewer conditions), whereas it increased among men at all ages and multimorbidity levels (with larger absolute increases typically at older ages and among those with 4 or fewer conditions).ConclusionsThere are sex and age differences in the impact of increasing chronic disease burden on changes in measures of multiple medication use among older adults. Though the drivers and health consequences of these trends warrant further investigation, the findings support the heterogeneity and complexity in the evolving association between multimorbidity and polypharmacy measures in older populations.

BackgroundAntiretroviral therapy (ART) success has led people to live longer with HIV/AIDS (PLWH) and thus be exposed to increasing risk of cardiovascular diseases (CVD). Hypertension (HTN), the biggest contributor to CVD burden, is a growing concern among PLWH. The current report describes the prevalence and predictors of HTN among PLWH in care in Cameroon.MethodsThis cross-sectional study included all PLWH aged 20 years and above who received care between 2016 and 2019 at one of the three Central Africa International Epidemiology Databases to Evaluate AIDS (CA-IeDEA) sites in Cameroon (Bamenda, Limbe, and Yaoundé). HTN was defined as blood pressure (BP) ≥140/90 mm Hg or self-reported use of antihypertensive medication. Logistic regressions models examined the relationship between HTN and clinical characteristics, and HIV-related factors.ResultsAmong 9,839 eligible PLWH, 66.2% were women and 25.0% had prevalent HTN [age-standardized prevalence 23.9% (95% CI: 22.2-25.6)], among whom 28 (1.1%) were on BP lowering treatment, and 6 of those (21.4%) were at target BP levels. Median age (47.4 vs. 40.5 years), self-reported duration of HIV infection (5.1 vs 2.8 years years), duration of ART exposure (4.7 vs 2.3 years), and CD4 count (408 vs 359 cell/mm3) were higher in hypertensives than non-hypertensives (all pConclusionAbout a quarter of these Cameroonian PLWH had HTN, driven among others by age and adiposity. Appropriate integration of HIV and NCDs services is needed to improve early detection, treatment and control of common comorbid NCD risk factors like hypertension and safeguard cardiovascular health in PLWH.

This study pointed to explore if variations in circulating levels of metabolites in the blood stream of no. 25 feral donkeys occur in view of the different coat color between specimens of Asinara (albino, no. 8) vs. Sardo (dun-grey, no. 17) breed. All individuals involved in this investigation are living in the nature, at Mediterranean latitudes and roam in the same areas all over the National Park of Capo Caccia, where they feed on spontaneous vegetation sources. The study was conducted during the positive photoperiod of the boreal hemisphere (peak in the month of June, 2019) to maximize the effect of exposure to the natural sun radiation and thus elicit the coping ability of albino (Asinara) in comparison with pigmented donkeys (Sardo). The biochemical profile of all donkeys was used in a Discriminant Analysis (DA) to explore if circulating levels of metabolites could point to metabolic markers for breed assignment of individuals following a canonical discriminant analysis (CANDISC). The biochemical investigation included also the determination of the circulating Vitamin E (alpha tocopherol, α-TOH), as an essential biologically active compound involved in antioxidant mechanisms, and its respective status (circulating α-TOH to total triglycerides and total cholesterol ratio). In the CANDISC, the distance between the two breeds was not significant. However, it pointed to different metabolites (UREA, total protein, total triglycerides, Zn) capable of describing biochemical patterns on each respective breed (Asinara vs. Sardo). The multivariate analysis DA carried out using 22 metabolites correctly assigned individuals to the two breeds in the 100% of cases. In view of such metabolic background, circulating α-TOH found in the bloodstream of Asinara vs. Sardo donkeys under free grazing conditions turned out to reach similar values (2.114 vs. 1.872 µg/ml, respectively, p = 0.676). It is worth noting that significant differences were observed as to circulating lactate dehydrogenase (LDH, p = 0.022) levels, in association with increased creatine phosphokinase (CPK, p = 0.076), both above the upper limit of the physiological range reported in other donkey breeds, and found in the totality of Asinara (albino) donkeys solely, still apparently clinically healthy.

Objective Assessment of enthesitis, a key feature in spondyloarthritis (SpA) and psoriatic arthritis (PsA), using objective and sensitive methods is pivotal in clinical trials. MRI allows detection of both soft tissue and intra-osseous changes of enthesitis. This article presents an atlas for the Outcome Measures in Rheumatology (OMERACT) Heel Enthesitis Magnetic Resonance ImagingMRI Scoring System (HEMRIS).Methods Following a preliminary selection of potential examples of each grade, as per HEMRIS definitions, the images along with detailed definitions and reader rules were discussed at web-based, interactive meetings between the members of the OMERACT MRI in Arthritis Working Group.Results Reference images of each grade of the MRI features to be assessed using HEMRIS, along with reader rules and recommended MRI sequences are depicted.Conclusion The presented reference images can be used to guide scoring Achilles tendon and plantar fascia (plantar aponeurosis) enthesitis according to the OMERACT HEMRIS in clinical trials and cohorts in which MRI enthesitis is used as an outcome.

Background/Purpose To evaluate biomarkers as predictors of impending erosion progression.Methods Variables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits. Generalised estimating equations (GEEs) evaluated the effect on REP of positive anticyclic citrullinated peptides (ACPAs) and/or rheumatoid factor (RF), C-reactive protein ˃8.0 mg/L (High-CRP) and 14-3-3η protein ≥0.50 ng/mL (High-14-3-3η), alone and in combinations.Results Out of 2155 evaluations in 749 consecutive patients, REP occurred after 186 (8.6%) visits, including 13 (2.2%) in patients recruited since 2010. Only 18/537 (3.4%; 6/411 (1.5%) in non-erosive vs 12/126 (9.5%) in patients already erosive) visits without any positive biomarker were followed by REP; at least one biomarker was positive prior to REP in 168/186 (90.3%) visits. Being positive for all four biomarkers conferred a positive predictive value (PPV) of 30.0% (RR 21.8) in patients non-erosive at the visit versus 35.5% (RR 3.07) in those already erosive. High-14-3-3η increased REP only in visits with High-CRP (eg, RR 2.5 to 3.9 when ACPA also positive) and in patients with non-erosive status (eg, RR from 4.3 to 9.4 when also High-CRP).Conclusions Adding High-14-3-3η to positive antibodies and CRP improves prediction of impending REP. Although REP is becoming rarer, signatures of biomarkers might help to adapt treatment strategies in at-risk individuals, even those already erosive.