Category: Nevin Manimala

Ann Surg. 2021 Aug 4. doi: 10.1097/SLA.0000000000005133. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to build a predictive model of operative difficulty in open liver resections (LRs).

SUMMARY BACKGROUND DATA: Recent attempts at classifying open-LR have been focused on postoperative outcomes and were based on predefined anatomical schemes without taking into account other anatomical/technical factors.

METHODS: Four intraoperative variables were perceived by the authors as to reflect operative difficulty: operation and transection times, blood loss, and number of Pringle maneuvers. A hierarchical ascendant classification (HAC) was used to identify homogeneous groups of operative difficulty, based on these variables. Predefined technical/anatomical factors were then selected to build a multivariable logistic regression model (DIFF-scOR), to predict the probability of pertaining to the highest difficulty group. Its discrimination/calibration was assessed. Missing data were handled using multiple imputation.

RESULTS: HAC identified 2 clusters of operative difficulty. In the “Difficult LR” group (20.8% of the procedures), operation time (401 min vs 243 min), transection time (150 vs.63 minute), blood loss (900 vs 400 mL), and number of Pringle maneuvers (3 vs 1) were higher than in the “Standard LR” group. Determinants of operative difficulty were body weight, number and size of nodules, biliary drainage, anatomical or combined LR, transection planes between segments 2 and 4, 4, and 8 or 7 and 8, nonanatomical resections in segments 2, 7, or 8, caval resection, bilioentric anastomosis and number of specimens. The c-statistic of the DIFF-scOR was 0.822. By contrast, the discrimination of the DIFF-scOR to predict 90-day mortality and severe morbidity was poor (c-statistic: 0.616 and 0.634, respectively).

CONCLUSION: The DIFF-scOR accurately predicts open-LR difficulty and may be used for various purposes in clinical practice and research.

PMID:34353987 | DOI:10.1097/SLA.0000000000005133

J Investig Med. 2021 Aug 5:jim-2020-001497. doi: 10.1136/jim-2020-001497. Online ahead of print.

ABSTRACT

Direct oral anticoagulants (DOACs) have become the treatment of choice in thromboembolism prophylaxis for non-valvular atrial fibrillation, surpassing warfarin. While interruption of DOAC therapy for various reasons is a common eventuality, the body of data from real-world clinical practice on the implications of such interruptions in different clinical settings is still limited. We assessed complication rates from DOAC (apixaban, rivaroxaban, dabigatran) interruption compared with warfarin in hospitalized patients. We performed a retrospective cohort analysis of electronic records of patients hospitalized in Rabin Medical Center between 2010 and 2017. Incidents of anticoagulation interruptions for various reasons (including unintended interruptions) were collected. DOAC-treated patients were excluded if they reported non-compliance, and warfarin-treated patients were excluded if their international normalized ratio measurement on admission was subtherapeutic. Outcomes included ischemic stroke, systemic thromboembolism, myocardial infarction, and all-cause mortality within 90 days of anticoagulation interruption. The median CHA2DS2-VASc score was 5.0 (IQR 4.0-6.0) in both treatment groups. The associated risk of stroke, thromboembolic complications, myocardial infarction, and all-cause mortality after interruption of anticoagulation was not significantly different between the 2 treatment groups. Selective comparison of patients who were well balanced on warfarin before treatment interruption to DOAC-treated patients did not significantly influence the outcomes. This study did not find a significant difference in the complication rate after interruption of DOAC therapy compared with interruption of warfarin therapy in hospitalized patients with a high risk of thromboembolism.

PMID:34353884 | DOI:10.1136/jim-2020-001497

Anat Cell Biol. 2021 Aug 6. doi: 10.5115/acb.21.101. Online ahead of print.

ABSTRACT

The atlas (C1) is known to present congenital anomalies in its anterior and posterior arches. The reported incidence of C1 anomalies is varied among the ethnic groups. We sought to determine the prevalence and various existing variations of C1 arch congenital anomalies in Omani subjects. This study was carried out by reviewing the cervical spine computed tomography scans of all the patients who had been referred to the Radiology Department, Sultan Qaboos University Hospital. Descriptive statistics and chi-square test were employed to analyse the data. A total of 663 subjects aged ≥18 years were included in the present study. Overall prevalence of C1 arch anomalies was 4.37% with 4.07% of isolated posterior arch anomalies, 0.3% of combined anterior and posterior arch anomalies. Among isolated posterior arch anomalies, type A and type B posterior arch defects were found in 3.77% and 0.3% of cases, respectively. Atlanto-occipital assimilation was noted in one case of total study subjects. The prevalence rate of C1 arch anomalies is relatively high in Omani subjects. The baseline data of C1 arch anomalies reported in the present study has a great impact on clinical practice, due to the fact that studying and evaluating the types of congenital anomalies helps in their accurate diagnosis and early intervention.

PMID:34353977 | DOI:10.5115/acb.21.101

J Neurol Neurosurg Psychiatry. 2021 Aug 5:jnnp-2021-326868. doi: 10.1136/jnnp-2021-326868. Online ahead of print.

ABSTRACT

BACKGROUND: Therapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer’s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet to be compared in detail in the genetic forms of FTD.

METHODS: The CDR+NACC FTLD and FRS were assessed cross-sectionally in 725 consecutively recruited participants from the Genetic FTD Initiative: 457 mutation carriers (77 microtubule-associated protein tau (MAPT), 187 GRN, 193 C9orf72) and 268 family members without mutations (non-carrier control group). 231 mutation carriers (51 MAPT, 92 GRN, 88 C9orf72) and 145 non-carriers had available longitudinal data at a follow-up time point.

RESULTS: Cross-sectionally, the mean FRS score was lower in all genetic groups compared with controls: GRN mutation carriers mean 83.4 (SD 27.0), MAPT mutation carriers 78.2 (28.8), C9orf72 mutation carriers 71.0 (34.0), controls 96.2 (7.7), p<0.001 for all comparisons, while the mean CDR+NACC FTLD Sum of Boxes was significantly higher in all genetic groups: GRN mutation carriers mean 2.6 (5.2), MAPT mutation carriers 3.2 (5.6), C9orf72 mutation carriers 4.2 (6.2), controls 0.2 (0.6), p<0.001 for all comparisons. Mean FRS score decreased and CDR+NACC FTLD Sum of Boxes increased with increasing disease severity within each individual genetic group. FRS and CDR+NACC FTLD Sum of Boxes scores were strongly negatively correlated across all mutation carriers (r_s=-0.77, p<0.001) and within each genetic group (r_s=-0.67 to -0.81, p<0.001 in each group). Nonetheless, discrepancies in disease staging were seen between the scales, and with each scale and clinician-judged symptomatic status. Longitudinally, annualised change in both FRS and CDR+NACC FTLD Sum of Boxes scores initially increased with disease severity level before decreasing in those with the most severe disease: controls -0.1 (6.0) for FRS, -0.1 (0.4) for CDR+NACC FTLD Sum of Boxes, asymptomatic mutation carriers -0.5 (8.2), 0.2 (0.9), prodromal disease -2.3 (9.9), 0.6 (2.7), mild disease -10.2 (18.6), 3.0 (4.1), moderate disease -9.6 (16.6), 4.4 (4.0), severe disease -2.7 (8.3), 1.7 (3.3). Sample sizes were calculated for a trial of prodromal mutation carriers: over 180 participants per arm would be needed to detect a moderate sized effect (30%) for both outcome measures, with sample sizes lower for the FRS.

CONCLUSIONS: Both the FRS and CDR+NACC FTLD measure disease severity in genetic FTD mutation carriers throughout the timeline of their disease, although the FRS may be preferable as an outcome measure. However, neither address a number of key symptoms in the FTD spectrum, for example, motor and neuropsychiatric deficits, which future scales will need to incorporate.

PMID:34353857 | DOI:10.1136/jnnp-2021-326868

BMJ Open Diabetes Res Care. 2021 Aug;9(1):e002177. doi: 10.1136/bmjdrc-2021-002177.

ABSTRACT

INTRODUCTION: Cost-effectiveness analyses are becoming increasingly important in Japan following the introduction of a health technology assessment scheme. The study objective was to develop an economic model to evaluate the cost-effectiveness of two interventions for type 2 diabetes in a Japanese population.

RESEARCH DESIGN AND METHODS: The Japan Diabetes Complications Study/Japanese Elderly Diabetes Intervention Trial risk engine (JJRE) Cost-Effectiveness Model (JJCEM) was developed, incorporating validated risk equations in Japanese patients with type 2 diabetes from the JJRE. Weibull regression models were developed for progression of the model outcomes, and a targeted literature review was performed to inform default values for utilities and costs. To illustrate outcomes, two simulated analyses were performed in younger (aged 40 years) and older (aged 80 years) Japanese populations, comparing a hypothetical treatment with placebo.

RESULTS: The model considers a population based on user-defined values for 11 baseline characteristic parameters and simulates rates of diabetic complications over a defined time horizon. Costs, quality-adjusted life years, and an incremental cost-effectiveness ratio are estimated. The model provides disaggregated results for two competing interventions, allowing visualization of the key drivers of cost and utility. A scatterplot of simulations and cost-effectiveness acceptability curve are generated for each analysis.

CONCLUSIONS: This is the first cost-effectiveness model for East Asian patients with type 2 diabetes, developed using Japan-specific risk equations. This population constitutes the largest share of the global population with diabetes, making this model highly relevant. The model can be used to evaluate the cost-effectiveness of anti-diabetic interventions in patients with type 2 diabetes in Japan and other East Asian populations.

PMID:34353881 | DOI:10.1136/bmjdrc-2021-002177

BMJ Open. 2021 Aug 5;11(8):e051208. doi: 10.1136/bmjopen-2021-051208.

ABSTRACT

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia.

METHODS: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant).

ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.

TRIAL REGISTRATION NUMBER: The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

PMID:34353808 | DOI:10.1136/bmjopen-2021-051208

BMJ Open. 2021 Aug 5;11(8):e049768. doi: 10.1136/bmjopen-2021-049768.

ABSTRACT

INTRODUCTION: Alzheimer’s disease has a high prevalence and a substantial impact on society, as well as the individual. Findings from clinical studies to date, suggest that multiple factors are likely to contribute to the variability seen in the progression of Alzheimer’s disease. However, despite this accumulating evidence, current identified factors do not explain the full extent of disease onset. Thus, the role of additional factors needs to be explored further.One such factor is exposure to adverse childhood experiences. However, the degree of this association is unknown. This systematic review will examine the literature investigating the associations between adverse childhood experiences and the risk of Alzheimer’s disease.

METHODS AND ANALYSIS: Articles investigating associations between exposure to adverse childhood experiences and the risk of Alzheimer’s disease will be identified systematically by searching CINAHL, MEDLINE and PsycInfo using Ebscohost. No restrictions on date of publication will be applied. The search strategy will be built combining the main key elements of the Population, Exposure, Comparator, and Outcomes inclusion criteria. A meta-analysis is planned and statistical methods will be used to identify and control for heterogeneity, if possible. The development of this protocol was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols.

ETHICS AND DISSEMINATION: Only published data will be used for this study, thus, ethical approval will not be required. Findings of the review will be published in a peer-reviewed scientific journal, and presented at national and international conferences.

PROSPERO REGISTRATION NUMBER: CRD42020191439.

PMID:34353804 | DOI:10.1136/bmjopen-2021-049768

BMJ Open. 2021 Aug 5;11(8):e050448. doi: 10.1136/bmjopen-2021-050448.

ABSTRACT

INTRODUCTION: Research has shown that improvements to the usability of medication alert systems are needed. For designers and decisions-makers to assess usability of their alert systems, two paper-based tools are currently available: the instrument for evaluating human-factors principles in medication-related decision support alerts (I-MeDeSA) and the tool for evaluating medication alerting systems (TEMAS). This study aims to compare the validity, usability and usefulness of both tools to identify their strengths and limitations and assist designers and decision-makers in making an informed decision about which tool is most suitable for assessing their current or prospective system.

METHODS AND ANALYSIS: First, TEMAS and I-MeDeSA will be translated into French. This translation will be validated by three experts in human factors. Then, in 12 French hospitals with a medication alert system in place, staff with expertise in the system will evaluate their alert system using the two tools successively. After the use of each tool, participants will be asked to fill in the System Usability Scale (SUS) and complete a survey on the understandability and perceived usefulness of each tool. Following the completion of both assessments, participants will be asked to nominate their preferred tool and relay their opinions on the tools. The design philosophy of TEMAS and I-MeDeSA differs on the calculation of a score, impacting the way the comparison between the tools can be performed. Convergent validity will be evaluated by matching the items of the two tools with respect to the usability dimensions they assess. SUS scores and answers to the survey will be statistically compared for I-MeDeSA and TEMAS to identify differences. Free-text responses in surveys will be analysed using an inductive approach.

ETHICS AND DISSEMINATION: Ethical approval is not required in France for a study of this nature. The results will be published in a peer-reviewed journal.

PMID:34353806 | DOI:10.1136/bmjopen-2021-050448

BMJ Open. 2021 Aug 5;11(8):e044070. doi: 10.1136/bmjopen-2020-044070.

ABSTRACT

INTRODUCTION: Rheumatic heart diseases (RHDs) contribute significant morbidity and mortality globally. To reduce the burden of RHD, timely initiation of secondary prophylaxis is important. The objectives of this study are to determine the frequency of subclinical RHD and to train a deep learning (DL) algorithm using waveform data from the digital auscultatory stethoscope (DAS) in predicting subclinical RHD.

METHODS AND ANALYSIS: We aim to recruit 1700 children from a group of schools serving the underprivileged over a 12-month period in Karachi (Pakistan). All consenting students within the age of 5-15 years with no underlying congenital heart disease will be eligible for the study. We will gather information regarding sociodemographics, anthropometric data, history of symptoms or diagnosis of rheumatic fever, phonocardiogram (PCG) and electrocardiography (ECG) data obtained from DAS. Handheld echocardiogram will be performed on each study participant to assess the presence of a mitral regurgitation (MR) jet (>1.5 cm), or the presence of aortic regurgitation (AR) in any view. If any of these findings are present, a confirmatory standard echocardiogram using the World Heart Federation (WHF) will be performed to confirm the diagnosis of subclinical RHD. The auscultatory data from digital stethoscope will be used to train the deep neural network for the automatic identification of patients with subclinical RHD. The proposed neural network will be trained in a supervised manner using labels from standard echocardiogram of the participants. Once trained, the neural network will be able to automatically classify the DAS data in one of the three major categories-patient with definite RHD, patient with borderline RHD and normal subject. The significance of the results will be confirmed by standard statistical methods for hypothesis testing.

ETHICS AND DISSEMINATION: Ethics approval has been taken from the Aga Khan University, Pakistan. Findings will be disseminated through scientific publications and to collaborators.

ARTICLE FOCUS: This study focuses on determining the frequency of subclinical RHD in school-going children in Karachi, Pakistan and developing a DL algorithm to screen for this condition using a digital stethoscope.

PMID:34353792 | DOI:10.1136/bmjopen-2020-044070

Arch Plast Surg. 2021 Jul;48(4):417-426. doi: 10.5999/aps.2020.02089. Epub 2021 Jul 15.

ABSTRACT

BACKGROUND: Soft tissue coverage plays a vital role in replacing the vascularity of the underlying bone in Gustilo type IIIB fractures. The aim of this article was to evaluate the feasibility of local pedicled flaps in type IIIB fractures at a tertiary care center.

METHODS: We included all cases of open Gustilo-Anderson type IIIB fractures of the tibia treated with local flap coverage from January 2017 to February 2019. We carried out a retrospective analysis to investigate the relationships of complications, hospital stay, and cost-effectiveness with the choice of flap, infective foci, site and size of the defect, and type of fixation.

RESULTS: Out of 138 Gustilo type IIIB fractures analyzed in our study, 27 cases had complications, of which 19 (13.76%) involved flap necrosis, four (2.89%) were infections, three (2.17%) involved partial necrosis, and one (0.72%) was related to bone spur development. Flap complications showed a statistically significant association with the perforator flap category (propeller flaps in particular) (P=0.001). Flap necrosis showed a significant positive correlation with cases treated within 3 weeks after trauma (P=0.046). A significant positive correlation was also found between defect size and the duration of hospital stay (P=0.03).

CONCLUSIONS: Although local flaps are harvested from the same leg that underwent trauma, their success rate is at least as high as microvascular flaps as reported from other centers. Amidst the local flaps, complications were predominantly associated with perforator flaps.

PMID:34352955 | DOI:10.5999/aps.2020.02089