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Abstract Background and Hypothesis People with first-episode psychosis (FEP) in low- and lower-middle-income countries (LMIC) experience delays in receiving treatment, resulting in poorer outcomes and higher mortality. There is robust evidence for effective and cost-effective early intervention in psychosis (EIP) services for FEP, but the evidence for EIP in LMIC has not been reviewed. We aim to review the evidence on early intervention for the management of FEP in LMIC. Study Design We searched 4 electronic databases (Medline, Embase, PsycINFO, and CINAHL) to identify studies describing EIP services and interventions to treat FEP in LMIC published from 1980 onward. The bibliography of relevant articles was hand-searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Study Results The search strategy produced 5074 records; we included 18 studies with 2294 participants from 6 LMIC countries. Thirteen studies (1553 participants) described different approaches for EIP. Pharmacological intervention studies (n = 4; 433 participants) found a high prevalence of metabolic syndrome among FEP receiving antipsychotics (P ≤ .005). One study found a better quality of life in patients using injectables compared to oral antipsychotics (P = .023). Among the non-pharmacological interventions (n = 3; 308 participants), SMS reminders improved treatment engagement (OR = 1.80, CI = 1.02–3.19). The methodological quality of studies evidence was relatively low. Conclusions The limited evidence showed that EIP can be provided in LMIC with adaptations for cultural factors and limited resources. Adaptations included collaboration with traditional healers, involving nonspecialist healthcare professionals, using mobile technology, considering the optimum use of long-acting antipsychotics, and monitoring antipsychotic side effects.

Background Public health and social measures (PHSM) intend to reduce the transmission of infectious diseases and to reduce the burden on health systems, economies and societies. During the COVID‐19 pandemic, PHSM have been selected, combined and implemented in a variable manner and inconsistently categorized in policy trackers. This paper presents an initial conceptual framework depicting how PHSM operate in a complex system, enabling a wide‐reaching description of these measures and their intended and unintended outcomes. Methods In a multi‐stage development process, we combined (i) a complexity perspective and systems thinking; (ii) literature on existing COVID‐19 PHSM frameworks, taxonomies and policy trackers; (iii) expert input and (iv) application to school and international travel measures. Results The initial framework reflects our current understanding of how PHSM are intended to achieve transmission‐related outcomes in a complex system, offering visualizations, definitions and worked examples. First, PHSM operate through two basic mechanisms, that is, reducing contacts and/or making contacts safer. Second, PHSM are defined not only by the measures themselves but by their stringency and application to specific populations and settings. Third, PHSM are critically influenced by contextual factors. The framework provides a tool for structured thinking and further development, rather than a ready‐to‐use tool for practice. Conclusions This conceptual framework seeks to facilitate coordinated, interdisciplinary research on PHSM effectiveness, impact and implementation; enable consistent, coherent PHSM monitoring and evaluation; and contribute to evidence‐informed decision‐making on PHSM implementation, adaptation and de‐implementation. We expect this framework to be modified and refined over time.

Introduction: After Alzheimer’s disease, frontotemporal lobar degeneration (FTLD) is the second most common form of early-onset dementia. Despite the heavy burden of care for FTLD, pharmacological and non-pharmacological treatments with sufficient efficacy remain scarce. This study aimed to evaluate the feasibility of a multimodal exercise program for FTLD and to examine preliminary changes in the clinical outcomes of the program in FTLD. Methods: This single-arm preliminary study was conducted from July 2017 to July 2018 and recruited 4 male patients with FTLD aged 60–78 years. Patients exercised under the supervision of an exercise instructor once every 2 weeks for 48 weeks. The multimodal exercise program comprised cognitive training, moderate-intensity continuous training, strength training, balance training, and flexibility and relaxation training. Feasibility was measured using dropout and attendance rates. Cognitive, psychological, physical, and behavioral function tests were conducted before and after the intervention. Results: All patients completed the intervention (100%) and attended well (93.6%). Positive changes in scores in the Stroop Color-Word Test (cognitive; 5 out of 6 items), Mood Check List-short form 2 (psychological), movement subscales of the Stereotypy Rating Inventory (behavioral), and Timed Up and Go (TUG, physical) assessments demonstrated a medium-to-high effect size (open effect size: 0.52–0.97). While there were improvements in some domains, such as recovery self-efficacy and exercise efficacy, the MMSE-J scores showed an overall slight decline, especially in the semantic dementia case where a marked decrease was observed. Additionally, three physical function items showed no effect, except for a positive outcome in the TUG test. Functional near-infrared spectroscopy revealed increased activation in the frontal lobe, indicated by elevated oxygenated hemoglobin levels before and after the exercise intervention. This pattern of activation suggests that the intervention may have stimulated neural activity in the frontal lobe, potentially enhancing cognitive and behavioral functions, including executive function and attention. Conclusion: The long-term multimodal exercise intervention may be feasible and positively change the cognitive, psychological, physical, and behavioral functions in older adults with FTLD. Although the intervention led to improvements in certain areas, there were also declines observed in various functions, which may not necessarily be due to the intervention itself but rather reflect the natural progression of the disease.

Background Subjective cognitive decline (SCD) is considered a risk factor for Alzheimer's disease (AD), highlighting the need for identifying and ranking effective interventions. This was addressed in a systematic review and network meta‐analysis (NMA) of pharmacological and non‐pharmacological interventions for SCD. Methods MEDLINE, Web of Science Core Collection, CENTRAL, and PsycINFO were searched for randomized controlled trials (RCTs) investigating effects on memory, global cognition, and quality of life. Random‐effect model NMAs were conducted. The Cochrane Risk‐of‐Bias‐2 tool assessed methodological quality. Prospero‐Registration: CRD42020180457. Results The systematic review included 56 RCTs. Education programs were most effective for improving memory, second most effective for improving global cognition. Quality of life and adverse events could not be included due to insufficient data. Overall methodological quality of studies was low. Conclusion Education programs were most effective for improving memory and cognition, warranting further research into effective elements of this intervention. There is urgent need to address identified methodological shortcomings in SCD intervention research.

Background The impact of non‐pharmacological interventions (NPIs) on asthma prevention and management is insufficiently examined. We aim to comprehensively evaluate and synthesize existing evidence regarding the effectiveness of various NPIs throughout the life course. Methods We conducted a systematic search and screening of reviews that examined the effectiveness of various NPIs on asthma prevention and control in the Cochrane Library, PubMed, Embase, and Ovid databases. Data extraction was performed by considering the type of NPIs and the life course stages of the target population. Recommendations were provided by considering the quality of review assessed using the AMSTAR2 tool and the consistency of findings across reviews. Results We identified 145 reviews and mapped the evidence on the impact of 25 subtypes of NPIs on asthma prevention and control based on five stages of life course. Reviews indicated a shift of focus and various impacts of major NPIs on asthma prevention and control across life courses, while a few types of NPIs, such as physical exercise, appeared to be beneficial in children, adolescents and adults. Consistent and high‐level evidence was observed only for psychological intervention on asthma control and quality of life among adults and older adults. Potential benefit with high‐level evidence was reported on certain NPIs, such as vitamin D in reducing risk of developing asthma in offsprings in the prenatal stage, digital health interventions in improving asthma control from childhood to older adulthood, and breathing exercise in improving quality of life, asthma‐related symptoms and lung function in adulthood and older adulthood. Conclusion This study emphasizes the significance of delivering NPIs to improve asthma prevention and management and highlights the heterogeneity regarding the impact of NPIs across life courses. High‐quality research is urgently needed to further strengthen the evidence base of NPIs and tailored interventions should be considered in guideline development.

Background Changes to the wound dressing frequently cause pain. Some adverse side effects of pharmacologic pain management may cause problems or even impede wound healing. There is no systematic study of non‐pharmacologic therapies for pain during wound dressing changes, despite the gradual promotion of non‐pharmacologic pain reduction methods. Objectives To give clinical wound pain management a new direction, locating and assessing non‐pharmacological interventions regarding pain brought on by wound dressing changes are necessary. Method The researchers conducted a comprehensive literature review on non‐pharmacological interventions for pain during wound dressing changes across five databases: PubMed, Web of Science, Medline, Embase, and the Cochrane Library spanning the period from January 2010 to September 2022. The evaluation of literature and data extraction was carried out independently by two researchers, and in cases of disagreement, a third researcher participated in the deliberation. To assess the risk of bias in the literature, the researchers utilised the Cochrane Handbook for Reviews of Interventions, version 5.1.0. Results In total, 951 people were involved in 11 investigations covering seven non‐pharmacological therapies. For pain triggered by dressing changes, virtual reality (VR) distraction, auditory and visual distractions, foot reflexology, religious and spiritual care, and guided imaging demonstrated partially positive effects, with hypnosis therapy and jaw relaxation perhaps having a weak effect. Conclusion The key to managing wounds is pain management. According to our review, there is some indication that non‐pharmacologic interventions can help patients feel less discomfort when having their wound dressings changed. However, the evidence supporting this view is weak. It needs to be corroborated by future research studies with multicentre and large samples. To promote and use various non‐pharmacologic interventions in the future, it is also necessary to build standardised and homogenised paths for their implementation.

Purpose To compare the effects of prevention interventions on delirium occurrence in critically ill adults. Methods MEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Cochrane Library, Prospero, and WHO international clinical trial registry were searched from inception to April 8, 2021. Randomized controlled trials of pharmacological, sedation, non-pharmacological, and multi-component interventions enrolling adult critically ill patients were included. We performed conventional pairwise meta-analyses, NMA within Bayesian random effects modeling, and determined surface under the cumulative ranking curve values and mean rank. Reviewer pairs independently extracted data, assessed bias using Cochrane Risk of Bias tool and evidence certainty with GRADE. The primary outcome was delirium occurrence; secondary outcomes were durations of delirium and mechanical ventilation, length of stay, mortality, and adverse effects. Results Eighty trials met eligibility criteria: 67.5% pharmacological, 31.3% non-pharmacological and 1.2% mixed pharmacological and non-pharmacological interventions. For delirium occurrence, 11 pharmacological interventions (38 trials, N  = 11,993) connected to the evidence network. Compared to placebo, only dexmedetomidine (21/22 alpha 2 agonist trials were dexmedetomidine) probably reduces delirium occurrence (odds ratio (OR) 0.43, 95% Credible Interval (CrI) 0.21–0.85; moderate certainty). Compared to benzodiazepines, dexmedetomidine (OR 0.21, 95% CrI 0.08–0.51; low certainty), sedation interruption (OR 0.21, 95% CrI 0.06–0.69; very low certainty), opioid plus benzodiazepine (OR 0.27, 95% CrI 0.10–0.76; very low certainty), and protocolized sedation (OR 0.27, 95% CrI 0.09–0.80; very low certainty) may reduce delirium occurrence but the evidence is very uncertain. Dexmedetomidine probably reduces ICU length of stay compared to placebo (Ratio of Means (RoM) 0.78, CrI 0.64–0.95; moderate certainty) and compared to antipsychotics (RoM 0.76, CrI 0.61–0.98; low certainty). Sedative interruption, protocolized sedation and opioids may reduce hospital length of stay compared to placebo, but the evidence is very uncertain. No intervention influenced mechanical ventilation duration, mortality, or arrhythmia. Single and multi-component non-pharmacological interventions did not connect to any evidence networks to allow for ranking and comparisons as planned; pairwise comparisons did not detect differences compared to standard care. Conclusion Compared to placebo and benzodiazepines, we found dexmedetomidine likely reduced the occurrence of delirium in critically ill adults. Compared to benzodiazepines, sedation-minimization strategies may also reduce delirium occurrence, but the evidence is uncertain.

INTRODUCTION Olfactory‐based cognitive training may be of benefit to individuals at risk of dementia given the strong association between olfactory impairment and cognitive decline. The Mind Your Nose (MYN) trial compared an olfactory‐based memory training protocol (OMT) to a visually‐based memory training protocol (VMT) among older adults with subjective cognitive decline. METHODS Participants (N = 53; 17 males; Mage = 72.77, standard deviation [SD] = 6.12) were randomly assigned in a 2:1 ratio to daily OMT (n = 36) or VMT (n = 17) intervention for 20 days. Outcomes were evaluated at baseline (T0), post‐intervention (T1), and 1‐month follow‐up (T2) and included standardized measures of global olfaction (Sniffin’ Sticks) and cognition (National Institutes of Health Toolbox), as well as performance on the olfactory memory (OM) and the visual memory (VM) tasks, and measures of mood and meta‐cognition. RESULTS A significant interaction was found between treatment allocation, time, and modality of memory task at T1(β = −37.50, p = 0.008) and T2(β = −28.75, p = 0.041). Post‐hoc comparisons revealed improvement in trained tasks; OMT led to improvement on the OM task (T1; g = 0.71, p = 0.036; T2; g = 0.72, p = 0.035), and VMT led to improvement on the VM task (T1; g = 1.22, p = 0.011; T2; g = 1.29, p = 0.006). Improvement on the untrained memory task only occurred in OMT (VM task, T1; g = 0.63, p = 0.071; T2; g = 0.74, p = 0.033). No interaction between treatment allocation and time was observed post intervention or at follow‐up for global olfactory ability (T1; β = 0.27, p = 0.871; T2; β = −1.27, p = 0.296). DISCUSSION Consistent with previous research, transfer gains from the OMT condition to an untrained VM task suggest that olfaction may contribute to a‐modal representations of memory. We argue that memory‐based olfactory training offers a new frontier for cognitive interventions among those at risk of dementia. Highlights Relatively few cognitive training programs engage the olfactory sense. Olfactory memory training offers a new frontier of cognitive training for older adults. Olfaction may contribute to improved performance on trained and untrained tasks. The functional impact of olfactory training should be further explored.

Abstract The present review will focus on the role of chloride anion in cardiovascular disease, with special emphasis in the development of hypertensive disease and vascular inflammation. It is known that acute and chronic overload of sodium chloride increase blood pressure and have pro-inflammatory and pro-fibrotic effects on different target organs, but it is unknown how chloride may influence these processes. Chloride anion is the predominant anion in the extracellular fluid and its intracellular concentration is dynamically regulated. As the queen of the electrolytes, it is of crucial importance to understand the physiological mechanisms that regulate the cellular handling of this anion including the different transporters and cellular chloride channels, which exert a variety of functions, such as regulation of cellular proliferation, differentiation, migration, apoptosis, intracellular pH and cellular redox state. In this article, we will also review the relationship between dietary, serum and intracellular chloride and how these different sources of chloride in the organism are affected in hypertension and their impact on cardiovascular disease. Additionally, we will discuss the approach of potential strategies that affect chloride handling and its potential effect on cardiovascular system, including pharmacological blockade of chloride channels and non-pharmacological interventions by replacing chloride by another anion.

In low and middle-income countries (LMICs), strict social distancing measures (e.g., nationwide lockdown) in response to the COVID-19 pandemic are unsustainable in the long-term due to knock-on socioeconomic and psychological effects. However, an optimal epidemiology-focused strategy for ‘safe-reopening’ (i.e., balancing between the economic and health consequences) remain unclear, particularly given the suboptimal disease surveillance and diagnostic infrastructure in these settings. As the lockdown is now being relaxed in many LMICs, in this paper, we have (1) conducted an epidemiology-based “options appraisal” of various available non-pharmacological intervention options that can be employed to safely lift the lockdowns (namely, sustained mitigation, zonal lockdown and rolling lockdown strategies), and (2) propose suitable application, pre-requisites, and inherent limitations for each measure. Among these, a sustained mitigation-only approach (adopted in many high-income countries) may not be feasible in most LMIC settings given the absence of nationwide population surveillance, generalised testing, contact tracing and critical care infrastructure needed to tackle the likely resurgence of infections. By contrast, zonal or local lockdowns may be suitable for some countries where systematic identification of new outbreak clusters in real-time would be feasible. This requires a generalised testing and surveillance structure, and a well-thought out (and executed) zone management plan. Finally, an intermittent, rolling lockdown strategy has recently been suggested by the World Health Organization as a potential strategy to get the epidemic under control in some LMI settings, where generalised mitigation and zonal containment is unfeasible. This strategy, however, needs to be carefully considered for economic costs and necessary supply chain reforms. In conclusion, while we propose three community-based, non-pharmacological options for LMICs, a suitable measure should be context-specific and based on: (1) epidemiological considerations, (2) social and economic costs, (3) existing health systems capabilities and (4) future-proof plans to implement and sustain the strategy.