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On the regional distribution of cerebral microvascular ‘raspberries’ and their association with cerebral atherosclerosis and acute circulatory failure

Cereb Circ Cogn Behav. 2023 Jan 7;4:100157. doi: 10.1016/j.cccb.2023.100157. eCollection 2023.

ABSTRACT

INTRODUCTION: In this follow-up study, cerebral microvascular formations termed ‘raspberries’ were quantified according to cerebral atherosclerosis (C-ASCL) and acute circulatory failure (ACF). We also examined the regional distribution of raspberries throughout the brain.

MATERIALS AND METHODS: The study population consisted of adult individuals who had undergone a diagnostic neuropathological autopsy. Groups were formed to examine the association between raspberries, C-ASCL and ACF (control group, C-ASCL group, C-ASCL+ACF group [n = 47 per group] and a combined C-ASCL-tot group [n = 94]). To examine the regional distribution, additional groups were formed based on previously known raspberry densities of the frontal cortex (high-, medium- and low-density group [n = 6 per group]). Raspberries were quantified on scanned haematoxylin-eosin-stained sections.

RESULTS: Cortical raspberry density did not differ at a statistically significant level between the control group, the C-ASCL group and the C-ASCL+ACF group (P = 0.10) but did so between the control group and the C-ASCL-tot group (P = 0.033). The total raspberry density of the high-, medium- and low-density groups differed at a statistically significant level (P = 0.005), which remained in group-to-group comparisons of the high- and medium-density groups (P = 0.015) and the high- and low-density groups (P = 0.002). Raspberries were rare in cerebral white matter and in the cerebellum.

CONCLUSION: An association between raspberry density and C-ASCL is supported but is weaker than previously indicated. An association with ACF is not indicated. The raspberry density of the frontal cortex provides an approximation of the brain’s total raspberry density.

PMID:36691600 | PMC:PMC9860404 | DOI:10.1016/j.cccb.2023.100157

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Spatiotemporal analysis of pertussis in Hunan Province, China, 2009-2019

BMJ Open. 2022 Sep 8;12(9):e055581. doi: 10.1136/bmjopen-2021-055581.

ABSTRACT

OBJECTIVES: This study aims to explore the spatial and spatiotemporal distribution of pertussis in Hunan Province, and provide a scientific basis for targeting preventive measures in areas with a high incidence of pertussis.

DESIGN: In this retrospective spatial and spatiotemporal (ecological) study, the surveillance and population data of Hunan Province from 2009 to 2019 were analysed. The ArcGIS V.10.3 software was used for spatial autocorrelation analysis and visual display, and SaTScan V.9.6 software was used for statistical analysis of spatiotemporal scan data.

SETTINGS: Confirmed and suspected pertussis cases with current addresses in Hunan Province and onset dates between 1 January 2009 and 31 December 2019 were included in the study.

PARTICIPANTS: The study used aggregated data, including 6796 confirmed and suspected pertussis cases.

RESULTS: The seasonal peak occurred between March and September, and scattered children were at high risk. The global Moran’s I was between 0.107 and 0.341 (p<0.05), which indicated that the incidence of pertussis in Hunan had a positive spatial autocorrelation. The results of local indicators of spatial autocorrelation analysis showed that the hot spots were mainly distributed in the northeast region of Hunan Province. Moreover, both purely space and spatiotemporal scans showed that the central and northeastern parts were the most likely cluster areas with an epidemic period between March and October in 2018 and 2019.

CONCLUSION: The distribution of the pertussis epidemic in Hunan Province from 2009 to 2019 shows spatiotemporal clustering. The clustering areas of the pertussis epidemic were concentrated in the central and northeastern parts of Hunan Province between March and October 2018 and 2019. In areas with low pertussis incidence, the strengthening of the monitoring system may reduce under-reporting. In areas with high pertussis incidence where we could study whether the genes of endemic pertussis strains are mutated and differ from vaccine strains.

PMID:36691220 | DOI:10.1136/bmjopen-2021-055581

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Association of area-level education with the regional growth trajectories of rates of antibacterial dispensing to patients under 3 years in Norway: a longitudinal retrospective study

BMJ Open. 2022 Sep 8;12(9):e058491. doi: 10.1136/bmjopen-2021-058491.

ABSTRACT

OBJECTIVE: To examine the association between area-level education and the local growth trajectories in antibacterial dispensing rates in Norwegian municipalities among children under 3 years old.

DESIGN: Retrospective, longitudinal study using individual primary care prescription data from the Norwegian Prescription Database for the period 2006-2016. Data were collected on the date of dispensing, the type and amount of antibiotic, the patient’s age, sex and municipality of residence and linked to municipality-level statistics on education available from Statistics Norway. We used multilevel growth curve modelling, with a linear trend variable modelled as a random effect and a cross-level interaction between linear trends and the proportion of the population in the municipality having received a university or college education.

SETTING: The local government level in Norway. The sample includes all municipalities over the study period.

OUTCOME MEASURE: Number of dispensed antibacterial prescriptions per 100 children in individual primary care by municipality and year.

RESULTS: We identified a significant negative linear trend in the square root of the dispensing rate for children under 3 years old during the period. This trend varied between municipalities. A negative cross-level interaction term between population education levels and random trends showed that municipalities with an average level of population education saw a reduction in their square root dispensing rates of -0.053 (95% CI -0.066 to -0.039) prescriptions per 100 children. Each additional percentage point in population education contributed a further -0.0034 (95% CI -0.006 to -0.001) reduction to the square root dispensing rate.

CONCLUSIONS: Municipalities in which a larger proportion of the local population have high educational achievements have been more successful in reducing antibacterial dispensing rates in children under 3 years old. Adopting area-level strategies and addressing local community disadvantages may help to optimise practices and prescribing patterns across local communities.

PMID:36691217 | DOI:10.1136/bmjopen-2021-058491

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SARS-CoV-2 chronological genomic evolution and epidemiology in the Middle East and North Africa (MENA) region as affected by vaccination, conflict and socioeconomical disparities: a population-based cohort study

BMJ Open. 2022 Sep 8;12(9):e060775. doi: 10.1136/bmjopen-2022-060775.

ABSTRACT

OBJECTIVE: To describe the chronological genomic evolution of SARS-CoV-2 and its impact on public health in the Middle East and North Africa (MENA) region.

METHODS: This study analysed all available SARS-CoV-2 genomic sequences, metadata and rates of COVID-19 infection from the MENA region retrieved from the Global Initiative on Sharing All Influenza Data database from January 2020 to August 2021. Inferential and ‎descriptive statistics were conducted to describe the epidemiology of SARS-CoV-2.

RESULTS: Genomic surveillance of SARS-CoV-2 in the MENA region indicated that the variants in January 2020 predominately belonged to the G, GR, GH or O clades and that the most common variant of concern was Alpha. By August 2021, however, the GK clade dominated (57.4% of all sequenced genomes), followed by the G clade (18.7%) and the GR clade (11.6%). In August, the most commonly sequenced variants of concern were Delta in the Middle East region (91%); Alpha (44.3%) followed by Delta (29.7%) and Beta (25.3%) in the North Africa region; and Alpha (88.9%), followed by Delta (10%) in the fragile and conflict-affected regions of MENA. The mean proportion of the variants of concern among the total sequenced samples differed significantly by country (F=1.93, P=0.0112) but not by major MENA region (F=0.14, P=0.27) or by vaccination coverage (F=1.84, P=0.176).

CONCLUSION: This analysis of the genomic surveillance of SARS-CoV-2 provides an essential description the virus evolution and its impact on public health safety in the MENA region. As of August 2021, the Delta variant showed a genomic advantage in the MENA region. The MENA region includes several fragile and conflict-affected countries with extremely low levels of vaccination coverage and little genomic surveillance, which may soon exacerbate the existing health crisis within those countries and globally.

PMID:36691215 | DOI:10.1136/bmjopen-2022-060775

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Effectiveness of public health interventions in reducing the prevalence of Opisthorchis viverrini: a protocol for systematic review and network meta-analysis

BMJ Open. 2022 Sep 8;12(9):e064573. doi: 10.1136/bmjopen-2022-064573.

ABSTRACT

INTRODUCTION: The carcinogenic liver fluke Opisthorchis viverrini is a major public health problem in the Mekong basin region. The liver flukes can induce cholangiocarcinoma, a bile duct cancer that causes a significant burden of mortality and economic loss. Various public health interventions have been conducted to reduce opisthorchiasis but the prevalence of O. viverrini remains high in endemic regions. The aim is to quantify the effectiveness of public health interventions in reducing the prevalence of O. viverrini infection.

METHODS AND ANALYSIS: Seven databases (including PubMed, SCOPUS, Web of Science, EMBASE, ScienceDirect, Thai thesis database and TCI (Thai journals online)) will be searched from initiation through to 2022 to identify studies of interventions to reduce the prevalence of O. viverrini infection. The prevalence, incidence or number of O. viverrini-infected people will be used as the source of O. viverrini prevalence data. A conventional meta-analysis and a Bayesian network meta-analysis will be conducted to undertake direct and indirect comparisons of different interventions. Meta-regression will be used to determine the effect of each intervention. The risk of bias will be assessed using the Cochrane Collaboration’s risk of bias tool. Heterogeneity between studies will be determined by forest plots and I2 and publication bias investigated with funnel plots and the Egger’s test.

ETHICS AND DISSEMINATION: Ethical approval will not be required because this study will only use published data. The final report of this review will be disseminated through publication in a peer-reviewed scientific journal and will also be presented at relevant conferences.

PROSPERO REGISTRATION NUMBER: CRD42022323066.

PMID:36691213 | DOI:10.1136/bmjopen-2022-064573

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Pharmacological interventions for hidradenitis suppurativa: a protocol for systematic review and network meta-analysis of randomised trials and non-randomised studies

BMJ Open. 2022 Sep 8;12(9):e062351. doi: 10.1136/bmjopen-2022-062351.

ABSTRACT

INTRODUCTION: Therapeutic recommendations for hidradenitis suppurativa (HS) have recently shifted towards non-invasive pharmacological options. Recent evidence has shown promising efficacy for specific treatments. However, data regarding the comparative efficacy of these treatments in patients with HS are still limited. Therefore, we plan to conduct a systematic review and network meta-analysis (NMA) to summarise the benefits and harms of different pharmacological interventions for treating people living with HS.

METHODS AND ANALYSIS: We will search electronic databases, including Medline, Embase, PubMed, Web of Science, Scopus, CINAHL and Cochrane Library beginning from their inception dates with no language restrictions. A grey literature search will be performed to supplement the electronic databases. Both randomised trials and non-randomised studies using validated measurement tools that investigated the benefits and harms of pharmacological interventions among people living with HS will be included. The predefined primary outcomes will include treatment responses that reflect the patient’s perspective and all-cause discontinuation. Screening, selection, extraction, assessment of the risk of bias and analysis of the strength of the evidence will be performed independently by a pair of reviewers. A two-step approach of traditional pairwise and NMA will be performed. Based on a random-effects model, standardised weighted mean differences and ORs with corresponding 95% CIs will be pooled as effect estimates for the continuous and categorical endpoints, respectively. Statistical and methodological heterogeneities will be assessed. Preplanned subgroup analyses and univariate meta-regression will be conducted to quantify the potential sources of heterogeneity. Evidence-based synthesis will be based on the magnitudes of effect size, evidence certainty and the surface under the cumulative ranking curve values.

ETHICS AND DISSEMINATION: Ethical approval is not required because this study is based on existing published data. These findings will be disseminated through scientific meetings and publications in peer-reviewed journals.

PROSPERO REGISTRATION NUMBER: CRD42022302795.

PMID:36691211 | DOI:10.1136/bmjopen-2022-062351

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Effectiveness of linkage to care and prevention interventions following HIV self-testing: a global systematic review and meta-analysis protocol

BMJ Open. 2022 Sep 8;12(9):e055688. doi: 10.1136/bmjopen-2021-055688.

ABSTRACT

INTRODUCTION: Early identification of persons living with HIV (PLWH) is crucial to institute timely treatment to prevent HIV-related morbidity and mortality. The convenience, flexibility and confidentiality of HIV self-testing enhance the acceptability of HIV testing and early detection of PLWH. However, persons who tested positive after a self-test are more likely to present late for treatment. This review seeks to evaluate the effectiveness of interventions to improve linkage to care and prevention after self-testing.

METHODS AND ANALYSIS: We will search PubMed, Embase, Web of Science, Cochrane Library, PsycInfo, Global Health Library, ClinicalTrials.gov and current controlled trials for all randomised and non-randomised studies published from 1 January 2010 to 31 July 2022 without language restriction. Two review authors will independently screen and select articles (based on the eligibility criteria for this review), extract data and assess the risk of bias in the included studies. Study-specific estimates will be converted to log risk ratios and weighted by the inverse of the variance of the log risk ratio before pooling into a fixed-effect model. The Cochrane’s Q χ2 test and the I2 statistic will be used to assess and quantify heterogeneity in the included studies, respectively. The Egger’s test and funnel plots will be used to assess publication bias. Sensitivity analysis will be conducted using leave-one-out analysis to assess the impact of outliers on the overall summary intervention effect.

ETHICS AND DISSEMINATION: No ethical clearance is needed for the current study as it will be based on already published articles. We will publish the findings of this study in international peer-reviewed journals and present them at conferences.

PMID:36691210 | DOI:10.1136/bmjopen-2021-055688

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A search for relevant contextual factors in intervention studies: a stepwise approach with online information

BMJ Open. 2022 Sep 9;12(9):e057048. doi: 10.1136/bmjopen-2021-057048.

ABSTRACT

OBJECTIVE: The aim of the present study is to describe a stepwise approach to study which contextual factors might moderate the effect of healthcare interventions and to test feasibility of this approach within the D-SCOPE project.

DESIGN: Exploratory case study.

SETTING: In the D-SCOPE project, a complex intervention by means of home visits was set up to improve access to tailored care in three municipalities (Ghent, Knokke-Heist and Tienen).

METHODS: One designed and tested an approach including five steps: (1) a theoretical/conceptual discussion of relevant contextual factor domains was held; (2) a search was done to find appropriate web-based public datasets which covered these topics with standardised information; (3) a list of all identified contextual factors was made (inventory); (4) to reduce the long list of contextual factors, a concise list of most relevant contextual factors was developed based on the opinion of two independent reviewers and (5) a nominal grouping technique (NGT) was applied.

RESULTS: Three public web-based datasets were found resulting in an inventory of 157 contextual factors. After the selection by two independent reviewers, 41 contextual factors were left over and presented in a NGT which selected 10 contextual factors. The NGT included seven researchers, all familiar with the D-SCOPE intervention, with various educational backgrounds and expertise and lasted approximately 1 hour.

CONCLUSION: The present study shows that a five-step approach is feasible to determine relevant contextual factors that might affect the results of an intervention study. Such information may be used to correct for in the statistical analyses and for interpretation of the outcomes of intervention studies.NCT03168204.

PMID:36691193 | DOI:10.1136/bmjopen-2021-057048

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Impact of targeted diabetic retinopathy training for graders in Vietnam and the implications for future diabetic retinopathy screening programmes: a diagnostic test accuracy study

BMJ Open. 2022 Sep 9;12(9):e059205. doi: 10.1136/bmjopen-2021-059205.

ABSTRACT

OBJECTIVES: To compare the accuracy of trained level 1 diabetic retinopathy (DR) graders (nurses, endocrinologists and one general practitioner), level 2 graders (midlevel ophthalmologists) and level 3 graders (senior ophthalmologists) in Vietnam against a reference standard from the UK and assess the impact of supplementary targeted grader training.

DESIGN: Diagnostic test accuracy study.

SETTING: Secondary care hospitals in Southern Vietnam.

PARTICIPANTS: DR training was delivered to Vietnamese graders in February 2018 by National Health Service (NHS) UK graders. Two-field retinal images (412 patient images) were graded by 14 trained graders in Vietnam between August and October 2018 and then regraded retrospectively by an NHS-certified reference standard UK optometrist (phase I). Further DR training based on phase I results was delivered to graders in November 2019. After training, a randomised subset of images from January to October 2020 (115 patient images) was graded by six of the original cohort (phase II). The reference grader regraded all images from phase I and II retrospectively in masked fashion.

PRIMARY AND SECONDARY OUTCOME MEASURES: Sensitivity was calculated at the two different time points, and χ2 was used to test significance.

RESULTS: In phase I, the sensitivity for detecting any DR for all grader groups in Vietnam was low (41.8-42.2%) and improved in phase II after additional training was delivered (51.3-87.2%). The greatest improvement was seen among level 1 graders (p<0.001), and the lowest improvement was observed among level 3 graders (p=0.326). There was a statistically significant improvement in sensitivity for detecting referable DR and referable diabetic macular oedema between all grader levels. The post-training values ranged from 40.0 to 61.5% (including ungradable images) and 55.6%-90.0% (excluding ungradable images).

CONCLUSIONS: This study demonstrates that targeted training interventions can improve accuracy of DR grading. These findings have important implications for improving service delivery in DR screening programmes in low-resource settings.

PMID:36691192 | DOI:10.1136/bmjopen-2021-059205

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Rate of glycaemic control and associated factors in patients with type 2 diabetes mellitus treated with insulin-based therapy at selected hospitals in Northwest Ethiopia: a multicentre cross-sectional study

BMJ Open. 2022 Sep 7;12(9):e065250. doi: 10.1136/bmjopen-2022-065250.

ABSTRACT

OBJECTIVES: This study was aimed to determine the level of glycaemic control and associated factors in patients with type 2 diabetes mellitus (T2DM) treated with insulin-based therapy.

DESIGNS: Institutional-based multicentre cross-sectional study design was employed to conduct this study.

SETTINGS: The diabetes follow-up clinics of selected hospitals in Northwest Ethiopia.

PARTICIPANTS: Adult patients with T2DM treated with insulin-based therapy at the selected hospitals who met the eligibility criteria were the study participants.

MAIN OUTCOME MEASURES: Good glycaemic control; when fasting blood glucose (FBG) level ranged from 70 to 130 mg/dL, and FBG <70 and >130 mg/dL was considered poor glycaemic control. A logistic regression model was used to identify determinants of poor glycaemic control. A p<0.05 at 95% CI was statistically significant.

RESULTS: Of 403 study participants, 54.8% were males with a mean age of 55.03±10.8 years. Though patients with T2DM were treated with insulin-based therapy, most of the participants (72.5%) could not achieve the target FBG. The overall mean FBG was 177.1±54.3, and far from the target glucose level. Patients who could not practise self-monitoring of blood glucose were found more likely to have poor glycaemic control compared with those who practised self-monitoring (p<0.001). Whereas patients who had a normal body mass index (p=0.011) and who were treated with premixed insulin-based therapy (p=0.04) were found less likely to have poor glycaemic control compared with patients with obesity and who received NPH insulin based-regimens, respectively.

CONCLUSION: This study demonstrated that a significant proportion of the study samples could not achieve glycaemic targets and the average blood glucose was far higher than the recommended glycaemic target level. Insulin initiation and titration, considering the determinants of glycaemic control, could be recommended to achieve target glycaemic levels.

PMID:36691186 | DOI:10.1136/bmjopen-2022-065250