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DELirium treatment with Transcranial Electrical Stimulation (DELTES): study protocol for a multicentre, randomised, double-blind, sham-controlled trial

BMJ Open. 2024 Nov 2;14(11):e092165. doi: 10.1136/bmjopen-2024-092165.

ABSTRACT

INTRODUCTION: Delirium, a clinical manifestation of acute encephalopathy, is associated with extended hospitalisation, long-term cognitive dysfunction, increased mortality and high healthcare costs. Despite intensive research, there is still no targeted treatment. Delirium is characterised by electroencephalography (EEG) slowing, increased relative delta power and decreased functional connectivity. Recent studies suggest that transcranial alternating current stimulation (tACS) can entrain EEG activity, strengthen connectivity and improve cognitive functioning. Hence, tACS offers a potential treatment for augmenting EEG activity and reducing the duration of delirium. This study aims to evaluate the feasibility and assess the efficacy of tACS in reducing relative delta power.

METHODS AND ANALYSIS: A randomised, double-blind, sham-controlled trial will be conducted across three medical centres in the Netherlands. The study comprises two phases: a pilot phase (n=30) and a main study phase (n=129). Participants are patients aged 50 years and older who are diagnosed with delirium using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria (DSM-5-TR), that persists despite treatment of underlying causes. During the pilot phase, participants will be randomised (1:1) to receive either standardised (10 Hz) tACS or sham tACS. In the main study phase, participants will be randomised to standardised tACS, sham tACS or personalised tACS, in which tACS settings are tailored to the participant. All participants will undergo daily 30 min of (sham) stimulation for up to 14 days or until delirium resolution or hospital discharge. Sixty-four-channel resting-state EEG will be recorded pre- and post the first tACS session, and following the final tACS session. Daily delirium assessments will be acquired using the Intensive Care Delirium Screening Checklist and Delirium Observation Screening Scale. The pilot phase will assess the percentage of completed tACS sessions and increased care requirements post-tACS. The primary outcome variable is change in relative delta EEG power. Secondary outcomes include (1) delirium duration and severity, (2) quantitative EEG measurements, (3) length of hospital stay, (4) cognitive functioning at 3 months post-tACS and (5) tACS treatment burden. Study recruitment started in April 2024 and is ongoing.

ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Committee of the Utrecht University Medical Center and the Institutional Review Boards of all participating centres. Trial results will be disseminated via peer-reviewed publications and conference presentations.

TRIAL REGISTRATION NUMBER: NCT06285721.

PMID:39488424 | DOI:10.1136/bmjopen-2024-092165

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Exploring the role of the built environment and psychosocial mediators on knee function in knee osteoarthritis patients in Singapore: a cross-sectional study

BMJ Open. 2024 Nov 2;14(11):e082625. doi: 10.1136/bmjopen-2023-082625.

ABSTRACT

OBJECTIVES: (1) To examine if a more accessible built environment (BE) is significantly associated with better knee function outcomes in knee osteoarthritis (OA) patients. (2) To assess if the relationship between BE and knee function is mediated by fear of movement and self-efficacy.

DESIGN: Cross-sectional study.

SETTING: Two tertiary hospitals in Singapore.

PARTICIPANTS: 212 knee OA patients (mean: 63.81±8.27 years old), majority female (69.8%).

INCLUSION CRITERIA: (i) meets National Institute for Health and Care Excellence criteria for knee OA, (ii) independent community ambulant.

EXCLUSION CRITERIA: (i) alternative diagnosis to knee OA, (ii) secondary osteoarthritis, (iii) severe medical and/or cognitive comorbidity impairing activities of daily living, (iv) previous knee arthroplasty, (v) wheelchair bound, or (vi) pregnant. PRIMARY AND SECONDARY OUTCOME MEASURES; STATISTICS: How self-efficacy (Arthritis Self-Efficacy Scale-8 (ASES-8)) and fear of movement (Brief Fear of Movement (BFOM)) mediates impact of overall BE (IPAQ-Environment module: Access to Destinations) and five item-specific domains of BE accessibility on knee function (Knee Injury and Osteoarthritis Outcome Score-12 (KOOS-12)). For variables significantly correlated with BE and KOOS-12 in bivariate Pearson correlation tests, mediation analysis was performed with confounders adjusted.

RESULTS: Total BE (r=0.142, p=0.038) and accessibility to transit station (r=0.161, p=0.019) were positively correlated with KOOS-12. Structural barriers (r=-0.138, p=0.045) were negatively correlated with KOOS-12. ASES-8 was a significant mediator in the relationship between accessibility to transit station and KOOS-12 (coeff=0.87, 95% CI=(0.24, 1.69), p=0.005) and between total BE and KOOS-12 (coeff=0.25, 95% CI=(0.10, 0.45), p=0.004). BFOM was a marginally significant mediator between structural barriers and KOOS-12 (coeff=-0.36, 95% CI=(-0.86, -0.02); p=0.054).

CONCLUSION: More accessible BE and lesser structural barriers in the BE are associated with better knee function. Self-efficacy mediates the relationship between overall BE accessibility and knee function. Fear of movement mediates the negative association between barriers in the BE and knee function.Applications include assessing BE barriers and psychosocial mediators in clinician consultations, developing multidisciplinary integrated care models and urban designers planning mobility friendly BEs.

TRIAL REGISTRATION NUMBER: The study has been registered under clinicaltrials.gov registry (Identifier: NCT04942236).

PMID:39488423 | DOI:10.1136/bmjopen-2023-082625

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Breast cancer and its determinants in Ethiopia: a systematic review and meta-analysis

BMJ Open. 2024 Nov 2;14(11):e080080. doi: 10.1136/bmjopen-2023-080080.

ABSTRACT

OBJECTIVES: Breast cancer is the leading cause of cancer morbidity and mortality among women. Still, there is a paucity of studies to know the magnitude of the problem in Ethiopia. Hence, this review was intended to pool the prevalence and identify the determinants of breast cancer in Ethiopia.

DESIGN: A systematic review and meta-analysis was conducted.

DATA SOURCES: Databases like PubMed/MEDLINE, HINARI, Science Direct, and Google Scholar, as well as websites of organisationsI organizations,rewere searched between 25 February and 6 March 2023.

ELIGIBILITY CRITERIA: All observational studies in Ethiopia that reported either the magnitude and/or determinants of breast cancer regardless of publication status were included.

DATA EXTRACTION AND SYNTHESIS: Two authors independently assessed and extracted the data. The Joanna Briggs Institute meta-analysis of statistics assessment and review instrument quality appraisal tool was used to assess the quality of the articles. Effect estimates were done by using the random-effects model. The meta-analysis results were displayed by using forest plots.

RESULTS: Seventeen articles were reviewed with 24 435 total participants. The pooled proportion of breast cancer morbidity among patients with cancer was 20. 58% (95% CI 17.25%, 23.90%) in Ethiopia. Consuming packed foods (POR=2.12, 95% CI 1.41, 3.17), presence of high cholesterol (POR=4.08; 95% CI 2.75, 6.07), physical inactivity (POR=3.27; 95% CI 1.80, 5.94), high body mass index (BMI) (POR=2.27; 95% CI 0.85, 6.03), postmenopause (POR=2.25; 95% CI 1.63, 3.10), family history of cancer (POR=3.65; 95% CI 0.85, 15.71) and lack of breastfeeding (POR=2.76; 95% CI 0.90, 7.92) were the determinants of breast cancer.

CONCLUSIONS: One of five patients with cancer is diagnosed with breast cancer in Ethiopia. Furthermore, more than a quarter of women with cancer suffer from breast cancer. Processed food consumption, high cholesterol in the body, lack of physical activity, high BMI, postmenopause, family history of cancer and lack of breastfeeding were the risk factors for breast cancer. The use of healthy food sources such as fruits and vegetables, and homegrown varieties of crops rather than seeking processed foods would help.

PROSPERO REGISTRATION NUMBER: CRD42023417733.

PMID:39488422 | DOI:10.1136/bmjopen-2023-080080

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Analysis of rational prescription of medicines by village clinics: a repeated cross-sectional study of a province in eastern China

BMJ Open. 2024 Nov 2;14(11):e081908. doi: 10.1136/bmjopen-2023-081908.

ABSTRACT

OBJECTIVE: To analyse the rational prescription of medicines by village clinics following China’s implementation of the New Healthcare System Reform (NHCSR).

DESIGN: Retrospective study.

SETTING: Village clinics in a province in eastern China.

PRIMARY AND SECONDARY OUTCOME MEASURES: Our evaluation was based on the core drug use indicators reported in the study ‘How to Investigate Drug Use in Health Facilities: Selected Drug Use Indicators‘.

RESULTS: The level of rational use of medicines (RUMs) in village clinics improved in 2018 compared with 2009; the average number of drugs per prescription decreased from 3.66 to 2.77, the percentage of prescriptions including antibiotics decreased from 65.40% to 46.00%, and the percentage of prescriptions including injections decreased from 55.75% to 37.48% (all p<0.01), whereas the percentage of drugs prescribed from the list of essential medicines increased from 66.50% to 80.34%, and the percentage of drugs prescribed by generic names increased from 61.29% to 70.65% (all p<0.01).

CONCLUSION: The level of RUMs improved after the implementation of the NHCSR, however, it was found that there was still a gap between the level of RUMs in 2018 and the international reference value. Financial investments, electronic prescription systems, improved supervision and regular training are essential actions that must be implemented.

PMID:39488421 | DOI:10.1136/bmjopen-2023-081908

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Importance of medical home domains on emergency visits using a cross-sectional national survey of US children

BMJ Open. 2024 Nov 2;14(11):e081533. doi: 10.1136/bmjopen-2023-081533.

ABSTRACT

BACKGROUND AND OBJECTIVES: Receiving care at patient-centred medical homes (PCMH) is associated with reduced emergency department (ED) visits among children. Adverse social determinants of health (SDoH), such as lower socioeconomic status and household poverty, are associated with increased ED visits in children. The objective of this study is to use machine learning techniques to understand the relative importance of each PCMH component among different populations with adverse SDoH on the outcome of ED visits.

METHODS DESIGN, SETTING AND PARTICIPANTS: This study used the 2018-2019 pooled data from the National Survey of Children’s Health (NSCH), an annual survey of parents and caregivers of US children from birth to 17 years. PCMH components were operationalised by classifying parent/caregiver responses into five domains: care coordination (CC), having a personal doctor or nurse, having a usual source of care, family-centred care and ease of getting referrals. SDoH included five categories: (1) social and community context, (2) economic stability, (3) education access and quality, (4) healthcare access and quality and (5) neighbourhood and built environment.

PRIMARY OUTCOME MEASURE: We used a split-improvement variable importance measure based on random forests to determine the importance of PCMH domains on ED visits overall and stratified by SDoH.

RESULTS: Overall, between 3% and 28% experienced one or more gaps in PCMH domains. Models show that problems with referrals (rank, 2; Gini, 83.5) and gaps in CC (rank, 3; Gini, 81.0) were the two most important domains of PCMH associated with ED visits in children. This result was consistent among black and Hispanic children and among children with lower socioeconomic status.

CONCLUSIONS: Our study findings underscore the importance of poor CC and referrals on ED visits for all children and those from disadvantaged populations. Initiatives for expanding the reach of PCMH should consider prioritising these two domains, especially in areas with significant minority populations.

PMID:39488420 | DOI:10.1136/bmjopen-2023-081533

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Association between myopia and sleep duration among primary school students in minority regions of Southwest China: a school-based cross-sectional research

BMJ Open. 2024 Nov 2;14(11):e083016. doi: 10.1136/bmjopen-2023-083016.

ABSTRACT

OBJECTIVE: To investigate the relationship between sleep duration and myopia among primary school students in minority regions of Southwest China.

METHODS: The school-based, cross-sectional study was conducted from October 2020 to January 2021. All participants underwent a comprehensive ocular examination and completed a questionnaire on demographic characteristics, ophthalmological history and major environmental factors for myopia. Spherical equivalent (SE) and ocular biometric parameters were measured after cycloplegia, with myopia being defined as SE ≤-0.5 D (Diopter). Multivariate regression models were used to examine the association of sleep duration with myopia, SE and axial length (AL).

RESULTS: A total of 857 students from grades 2 to 4 were included in the analysis, of which 63.6% were myopic and 62.0% belonged to ethnic minorities. Boys had a slightly higher prevalence of myopia compared with girls (66.7% vs 60.6%, p=0.06). Myopic students had longer AL, deeper anterior chamber depth and thinner central corneal thickness compared with non-myopic students (all p<0.05). There was no significant association between sleep duration and myopia in both boys and girls (p=0.319 and 0.186, respectively). Moreover, girls with a sleep duration of 8-9 hour/day had higher SE and shorter AL compared with those with less than 8 hour/day of sleep (β=0.41 and -0.32, respectively, all p<0.05).

CONCLUSION: This cross-sectional study did not find a significant association between sleep duration and myopia. However, it suggests that 8-9 hours of sleep per day may have a protective effect on SE progression and AL elongation in girls. Future studies with objectively measured sleep duration are needed to validate the findings.

PMID:39488419 | DOI:10.1136/bmjopen-2023-083016

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Barriers and facilitators to antenatal care services utilisation in Somaliland: a qualitative study

BMJ Open. 2024 Nov 2;14(11):e085073. doi: 10.1136/bmjopen-2024-085073.

ABSTRACT

OBJECTIVE: To explore the barriers and facilitators of antenatal care (ANC) utilisation in Somaliland.

DESIGN: An exploratory qualitative study design.

SETTING: Various settings were considered for study including maternal and child health clinics, hospitals and community.

METHODS: 74 study participants including 33 pregnant women, 22 healthcare providers, 10 community elders and ten religious leaders were purposively selected. Data was collected via focus group discussion and in-depth interviews in the local Somali language. The data was audio recorded, transcribed verbatim, translated into English and imported into NVivo V.12 software. Thematic framework analysis was used to assess barriers and facilitators of ANC utilisation.

RESULTS: Six main themes were identified as barriers of ANC utilisation. These include lack of awareness, long distance and lack of transportation access, economic barriers, lack of social support, beliefs and thoughts and health facility-related factors such as caregivers approach, waiting time and inadequate skill of providers. Proper dissemination of ANC information, adequate spousal support and cheap pricing of services were found to be facilitators of ANC uptake.

CONCLUSION: A strategy that focuses on raising awareness about ANC, making it accessible by reducing the cost-of-service charge, encouraging partner involvement, improving the quality of services and making it customer-friendly will help to overcome the barriers of antenatal utilisation.

PMID:39488416 | DOI:10.1136/bmjopen-2024-085073

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Mass spectrometry-based proteomics to study mutants and interactomes of mitochondrial translocation proteins

Methods Enzymol. 2024;707:101-152. doi: 10.1016/bs.mie.2024.07.059. Epub 2024 Aug 23.

ABSTRACT

The multiple functions of mitochondria are governed by their proteome comprising 1000-1500 proteins depending on the organism. However, only few proteins are synthesized inside mitochondria, whereas most are “born” outside mitochondria. To reach their destined location, these mitochondrial proteins follow specific import routes established by a mitochondrial translocase network. A detailed understanding of the role and interplay of the different translocases is imperative to understand mitochondrial biology and how mitochondria are integrated into the cellular network. Mass spectrometry (MS) proved to be effective to study the translocase network regarding composition, functions, interplay, and cellular responses evoked by dysfunction. In this chapter, we provide protocols tailored to MS-enabled functional analysis of mutants and interactomes of mitochondrial translocation proteins. In the first part, we exemplify the MS-based proteomics analysis of translocation mutants for delineating the human mitochondrial importome following depletion of the central translocation protein TOMM40. The protocol comprises metabolic stable isotope labeling, TOMM40 knockdown, preparation of mitochondrial fractions, and sample preparation for liquid chromatography (LC)-MS. For deep MS analysis, prefractionation of peptide mixtures by high pH reversed-phase LC is described. In the second part, we outline an affinity purification MS approach to reveal the association of an orphaned protein with the translocase TIM23. The protocol covers FLAG-tag affinity purification of protein complexes from mitochondrial fractions and downstream sample preparation for interactome analysis. In the last unifying part, we describe methods for LC-MS, data processing, statistical analysis and visualization of quantitative MS data, and provide a Python code for effective, customizable analysis.

PMID:39488372 | DOI:10.1016/bs.mie.2024.07.059

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Iatrogenic emboli during mechanical thrombectomy for acute ischemic stroke: comparison between stent retriever technique and contact aspiration-a retrospective case-control study

J Neurointerv Surg. 2024 Nov 2:jnis-2024-022206. doi: 10.1136/jnis-2024-022206. Online ahead of print.

ABSTRACT

BACKGROUND: Mechanical thrombectomy (MT) is an effective treatment for acute ischemic stroke from large vessel occlusion (LVO). While embolization to a new territory (ENT) after MT is well-documented, data on embolization in the same distal territory (EDT) are limited. Achieving modified Treatment In Cerebral Infarction (mTICI) 3 reperfusion presents significant clinical benefits over mTICI 2b/2c, necessitating strategies to reduce both ENT and EDT. Previous studies suggest higher rates of EDTs with contact aspiration compared with stentrievers. However, comprehensive comparison studies in clinical practice are scarce. This study compares the rates of overall clot emboli (OCE) between these MT strategies.

METHODS: A retrospective, multicenter observational study was conducted at four university hospitals in France from January 2015 to November 2019. Adult patients (≥18 years) with acute ischemic stroke due to LVO, treated with either contact aspiration (ADAPT, A Direct Aspiration First Pass Technique) or stentrievers, specifically using the Embotrap device to maintain sample homogeneity, were included. Digital subtraction angiography was used for imaging, with two independent, blinded reviewers assessing OCE post-first MT pass. Propensity score full matching and independent sample testing were employed to evaluate OCE after the first MT pass.

RESULTS: A significant difference in OCE rates was observed between contact aspiration and stentriever techniques, with the stentriever technique resulting in fewer embolic events compared with ADAPT, based on a propensity score analysis that accounts for key confounding factors.

CONCLUSION: A statistically significant reduction in embolic events was observed with the stentriever technique compared with contact aspiration. These results suggest that the stentriever method may offer a safer profile in terms of embolic risk for LVO interventions, and should be considered over contact aspiration when embolic risk is a primary concern, while also considering individual patient factors.

PMID:39488338 | DOI:10.1136/jnis-2024-022206

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Radiographic Predictors of Postoperative Inferior Alveolar Nerve Injury in Mandibular Third Molar Surgery

J Oral Maxillofac Surg. 2024 Oct 16:S0278-2391(24)00866-8. doi: 10.1016/j.joms.2024.10.004. Online ahead of print.

ABSTRACT

BACKGROUND: Cone-beam computed tomography (CBCT) provides additional 3-dimensional information on the relationship between the mandibular third molar (M3M) and the inferior alveolar nerve (IAN). As such, CBCT is being increasingly utilized in preoperative M3M assessment.

PURPOSE: The purpose of the study was to compare the radiographic findings on panoramic and CBCT and their association with postoperative IAN paresthesia.

STUDY DESIGN, SETTING, SAMPLE: We conducted a retrospective cohort study in a sample of patients referred to the Department of Oral and Maxillofacial Surgery at the Royal Dental Hospital of Melbourne, for management of impacted M3Ms. Patients were included in this study if they had 1 or more high-risk findings on orthopantomogram (OPG), had both OPG and CBCT imaging taken and if at least 1 M3M had been extracted. Subjects were excluded from this study if their M3Ms were not extracted or if a CBCT was not indicated.

INDEPENDENT VARIABLE: The independent variable was radiographic features identified on OPG (Rood and Shehab’s radiographic signs, root morphology, impaction type, Pell and Gregory classification) and CBCT (number and location of roots, severity of IAN compression and the presence of ankylosis).

MAIN OUTCOME VARIABLE: The outcome variable was postoperative neurosensory function defined as any reported paresthesia at 2-week postprocedural review.

COVARIATES: The covariates were patient demographic information (age, sex).

ANALYSES: Variables were initially assessed with univariate logistic regression analysis to determine factors related to developing postoperative paresthesia. Multivariate logistic regression analysis was then used to assess the association between positive univariate study variables and postoperative paresthesia, while adjusting for potential confounders. Covariates were assessed using an omnibus likelihood ratio test and included if they were statistically significant at the P < .05 level.

RESULTS: The study sample consisted of 257 subjects who underwent surgical removal of n = 386 M3Ms. The mean age was 25.9 (SD = 7.05). The panoramic features of narrowing of canal, diversion of canal and dark/bifid roots were identified as statistically significant associations of postoperative paresthesia. No CBCT features were significantly associated of postoperative paresthesia.

CONCLUSION AND RELEVANCE: Certain panoramic features, along with patient age, are significant predictors of IAN paresthesia. CBCT findings were not significant predictors upon multivariate analysis, thus additional CBCT imaging did not significantly improve ability to predict paresthesia.

PMID:39488334 | DOI:10.1016/j.joms.2024.10.004