Category: Nevin Manimala

BMJ Open. 2021 May 25;11(5):e042821. doi: 10.1136/bmjopen-2020-042821.

ABSTRACT

AIMS: To evaluate the type 2 diabetes mellitus (T2DM) risk of individuals with different types of dyslipidaemia and compare the predictive value of distinct lipid parameters in predicting T2DM.

METHODS: We conducted a secondary analysis of data from the China Health and Retirement Longitudinal Study (CHARLS). 17 708 individuals over 45 years old were interviewed, and 11 847 blood samples were collected at the baseline survey (2011-2012). Outcome of T2DM was confirmed during two follow-up surveys (2013-2014 and 2015-2016). The HRs and 95% CI of T2DM associated with dyslipidaemia were estimated by Cox proportional hazards regressions model. The discriminatory value of eight lipid parameters were compared by the area under the receiver operating characteristic (ROC) curve (AUC).

RESULTS: A total of 7329 participants were enrolled in our analysis; during the mean follow-up time of 3.4 years, 387 (5.28%) participants developed new-onset diabetes. Compared with participants in normal lipid levels, the T2DM risk of those with hypercholesterolaemia, hypertriglyceridaemia and low high-density lipoprotein cholesterol (HDL-C) were significantly increased (HRs (95% CI) were 1.48 (1.11 to 1.96), 1.92 (1.49 to 2.46) and 1.67 (1.35 to 2.07), respectively). The AUCs of non-HDL-C (0.685, 95% CI 0.659 to 0.711), triglyceride (TG) (0.684, 95% CI 0.658 to 0.710), total cholesterol (TC)/HDL-C (0.685, 95% CI 0.659 to 0.712) and TG/HDL-C (0.680, 95% CI 0.654 to 0.706) were significantly (p<0.005) larger than that of other lipid parameters.

CONCLUSION: Middle-aged and elderly adults with hypertriglyceridaemia, hypercholesterolaemia and low HDL-C were at higher risk for developing diabetes. Non-HDL-C, TG, TC/HDL and TG/HDL have greater performance than other lipid parameters in predicting T2DM incidence.

PMID:34035089 | DOI:10.1136/bmjopen-2020-042821

BMJ Open. 2021 May 25;11(5):e045559. doi: 10.1136/bmjopen-2020-045559.

ABSTRACT

INTRODUCTION: As a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).

METHODS AND ANALYSIS: The study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.

ETHICS AND DISSEMINATION: The protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.

TRIAL REGISTRATION NUMBER: NCT03539445.

PMID:34035100 | DOI:10.1136/bmjopen-2020-045559

BMJ Open Diabetes Res Care. 2021 May;9(1):e002150. doi: 10.1136/bmjdrc-2021-002150.

ABSTRACT

INTRODUCTION: The aim of the study was to develop and validate a clinical prediction rule (CPR) for foot ulceration in people with diabetes.

RESEARCH DESIGN AND METHODS: Development of a CPR using individual participant data from four international cohort studies identified by systematic review, with validation in a fifth study. Development cohorts were from primary and secondary care foot clinics in Europe and the USA (n=8255, adults over 18 years old, with diabetes, ulcer free at recruitment). Using data from monofilament testing, presence/absence of pulses, and participant history of previous ulcer and/or amputation, we developed a simple CPR to predict who will develop a foot ulcer within 2 years of initial assessment and validated it in a fifth study (n=3324). The CPR’s performance was assessed with C-statistics, calibration slopes, calibration-in-the-large, and a net benefit analysis.

RESULTS: CPR scores of 0, 1, 2, 3, and 4 had a risk of ulcer within 2 years of 2.4% (95% CI 1.5% to 3.9%), 6.0% (95% CI 3.5% to 9.5%), 14.0% (95% CI 8.5% to 21.3%), 29.2% (95% CI 19.2% to 41.0%), and 51.1% (95% CI 37.9% to 64.1%), respectively. In the validation dataset, calibration-in-the-large was -0.374 (95% CI -0.561 to -0.187) and calibration slope 1.139 (95% CI 0.994 to 1.283). The C-statistic was 0.829 (95% CI 0.790 to 0.868). The net benefit analysis suggested that people with a CPR score of 1 or more (risk of ulceration 6.0% or more) should be referred for treatment.

CONCLUSION: The clinical prediction rule is simple, using routinely obtained data, and could help prevent foot ulcers by redirecting care to patients with scores of 1 or above. It has been validated in a community setting, and requires further validation in secondary care settings.

PMID:34035053 | DOI:10.1136/bmjdrc-2021-002150

BMJ Open. 2021 May 25;11(5):e041472. doi: 10.1136/bmjopen-2020-041472.

ABSTRACT

OBJECTIVES: Several epidemiological models have been published to forecast the spread of the COVID-19 pandemic, yet many of them have proven inaccurate for reasons that remain to be fully determined. We aimed to develop a novel model and implement it in a freely accessible web application.

DESIGN: We built an SIR-type compartmental model with two additional compartments: D (deceased patients); L (individuals who will die but who will not infect anybody due to social or medical isolation) and integration of a time-dependent transmission rate and a periodical weekly component linked to the way in which cases and deaths are reported.

RESULTS: The model was implemented in a web application (as of 2 June 2020). It was shown to be able to accurately capture the changes in the dynamics of the pandemic for 20 countries whatever the type of pandemic spread or containment measures: for instance, the model explains 97% of the variance of US data (daily cases) and predicts the number of deaths at a 2-week horizon with an error of 1%.

CONCLUSIONS: In early performance evaluation, our model showed a high level of accuracy between prediction and observed data. Such a tool might be used by the global community to follow the spread of the pandemic.

PMID:34035086 | DOI:10.1136/bmjopen-2020-041472

Genome Res. 2021 May 25:gr.271288.120. doi: 10.1101/gr.271288.120. Online ahead of print.

ABSTRACT

Recent technological advances have enabled spatially resolved measurements of expression profiles for hundreds to thousands of genes in fixed tissues at single-cell resolution. However, scalable computational analysis methods able to take into consideration the inherent 3D spatial organization of cell types and nonuniform cellular densities within tissues are still lacking. To address this, we developed MERINGUE, a computational framework based on spatial auto-correlation and cross-correlation analysis to identify genes with spatially heterogeneous expression patterns, infer putative cell-cell communication, and perform spatially informed cell clustering in 2D and 3D in a density-agnostic manner using spatially resolved transcriptomics data. We applied MERINGUE to a variety of spatially resolved transcriptomics datasets including multiplexed error-robust fluorescence in situ hybridization (MERFISH), spatial transcriptomics, Slide-Seq, and aligned in situ hybridization (ISH) data. We anticipate that such statistical analysis of spatially resolved transcriptomics data will facilitate our understanding of the interplay between cell state and spatial organization in tissue development and disease.

PMID:34035045 | DOI:10.1101/gr.271288.120

BMJ Health Care Inform. 2021 May;28(1):e100305. doi: 10.1136/bmjhci-2020-100305.

ABSTRACT

Unscheduled admissions to hospital place great demands on the use of limited healthcare resources in health systems worldwide. A range of approaches exist to manage demand; however, interventions within hospitals have received less attention, and the evidence base on effectiveness is limited. This study aimed to assess the effectiveness of a novel intervention, implemented in National Health Service Lothian, to reduce the number of unscheduled attendances, and to estimate the impact on hospital admissions, length of hospital stay and overall total acute hospital costs.

METHODS: Before and after observational study of an anticipatory care planning intervention targeted among people identified by a prediction algorithm (Scottish Patients at Risk of Readmission and Admission) as being at high risk of future unscheduled hospital admissions. The statistical significance of the difference in outcomes observed before and after implementation of the intervention between August 2014 and July 2015 was tested using difference-in-difference analysis.

RESULTS: The intervention was estimated to reduce the number of unscheduled hospital admissions and emergency department (ED) visits by approximately 0.36 (95% CI -0.905 to 0.191) per patient per year (based on 954 and 450 patients in the intervention and control groups, respectively). There was also non-significant reductions in length of hospital stay for unscheduled admissions and hospital costs for ED visits and inpatient care. The overall predicted effect of the intervention for the average participant was a saving of around £2912 (95% CI -7347.0 to 1523.9) per patient per year.

CONCLUSION: An anticipatory care planning intervention focused among people judged to be at higher risk of future unscheduled hospital admissions can be effective in reducing the number of unscheduled admissions to hospital and ED visits, and may lead to an overall saving in use of hospital resources.

PMID:34035049 | DOI:10.1136/bmjhci-2020-100305

Oral Surg Oral Med Oral Pathol Oral Radiol. 2021 Mar 5:S2212-4403(21)00129-2. doi: 10.1016/j.oooo.2021.02.019. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the expression of chemokine-like factor superfamily 6 (CMTM6) and programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) in oral squamous cell carcinoma (OSCC) and to further explore its clinical significance in OSCC.

STUDY DESIGN: Samples of 44 OSCC and paracancerous tissues were investigated. We estimated the expression of the 3 proteins by immunohistochemistry and further detected mRNA expression by quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS: Immunohistochemistry results demonstrated that the positive expression of CMTM6 and PD-1/PD-L1 in OSCC tissues was significantly higher than that in paracancerous tissues. Statistical significance was found between the 2 groups (all P < .05). Moreover, PD-L1 expression was related to OSCC clinical stage and lymph node metastasis (P < .05). The qRT-PCR results confirmed that the relative expression of CMTM6 and PD-1/PD-L1 mRNA in OSCC tissues was significantly higher than that in paracancerous tissues (all P < .05), and Spearman rank correlation showed that there was a significant relationship between mRNA and protein expression (all P < .05).

CONCLUSIONS: CMTM6 and PD-1/PD-L1 were upregulated in OSCC, and CMTM6 may play a synergistic role with PD-1/PD-L1 in the immune pathway. Therefore, we believe that CMTM6 and PD-1/PD-L1 will become checkpoints for immunotherapy of OSCC.

PMID:34034998 | DOI:10.1016/j.oooo.2021.02.019

J Nutr Educ Behav. 2021 May 22:S1499-4046(21)00078-6. doi: 10.1016/j.jneb.2021.02.009. Online ahead of print.

ABSTRACT

OBJECTIVE: To use the Theory of Planned Behavior (TPB) to assess mothers’ behavioral intentions to provide toddlers with a healthy diet and see if the addition of the parental role construction (PRC) variable strengthened the TPB.

DESIGN: An online survey using data gathered from preliminary research and a previously validated survey.

PARTICIPANTS: The final sample consisted of 148 mothers. The mean age was 32.8 (SD = 6.16) years. Most participants were married (87.2%), had earned a college degree or higher (79.7%), held part-time or full-time employment (60.8%), and White (90.3%).

MAIN OUTCOME MEASURES: The TPB constructs, PRC, and the mothers’ behavioral intentions surrounding toddler feeding.

ANALYSIS: The determinants of intention per the TPB were explored using descriptive statistics and multiple linear regression.

RESULTS: The TPB model predicted 53% of the variance in mother’s behavioral intention to provide their toddler with a healthy diet. The addition of the PRC variable added 6% more predictive power to the model.

CONCLUSIONS AND IMPLICATIONS: Mothers’ behavioral intentions surrounding feeding their toddlers were strongly influenced by the TPB constructs and their perceptions of the maternal role. Health promotion efforts should aim to increase the mother’s sense of behavioral control and parental responsibility rather than focusing on the benefits of healthy eating.

PMID:34034983 | DOI:10.1016/j.jneb.2021.02.009

Curr Probl Cancer. 2021 May 16:100758. doi: 10.1016/j.currproblcancer.2021.100758. Online ahead of print.

ABSTRACT

OBJECTIVES: Conflicting data have been published regarding the prognostic impact of the t(1;19)/TCF3-PBX1 translocation in childhood ALL. The objective of this study was to explore the correlation between the TCF3-PBX1 fusion gene and clinical outcome in Chinese children with newly diagnosed ALL.

METHODS: In order to address this issue in our setting, we summarized and analyzed the data of 837 Chinese children with ALL diagnosed between 2010 and 2017. All the patients were treated with the National Protocol of Childhood Leukemia in China (NPCLC)-ALL-2008 protocol. Clinical characteristics and prognosis of pediatric ALL patients with or without TCF3-PBX1 rearrangement were analyzed and compared retrospectively.

RESULTS: The TCF3-PBX1 fusion gene was identified in 48 (5.7%) of 837 children with ALL. Our results showed that TCF3-PBX1 positive patients had higher pretreatment white blood cell counts, higher PB blasts percentages and worse risk classification at diagnosis. No statistically significant differences in CR rates, response to prednisone and relapse rates were found between TCF3-PBX1-positive and -negative patients. The 5-year predicted EFS, RFS, and OS of the TCF3-PBX1 positive group compared with the control group were 86.2%±5.3% vs 85.4%±1.3% (P=0.657), 88.2%±5.1% vs 92.2%±1.0% (P=0.458) and 90.4%±4.6% vs 89.0%±1.1% (P=0.561), respectively. No differences were observed regarding clinical outcome between these two groups. When compared with standard risk, intermediate risk and high risk group patients, the long-term survival of TCF3/PBX1 positive group was approximately similar to that of the intermediate risk group under the same protocol in our single center.

CONCLUSION: In contrast to previous studies, childhood ALL patients with TCF3-PBX1 transcripts do not appear to show a better outcome than their negative counterparts. TCF3/PBX1 positive was a definitive intermediate risk factor with our NPCLC-ALL-2008 protocol.

PMID:34034913 | DOI:10.1016/j.currproblcancer.2021.100758

Eur J Surg Oncol. 2021 May 10:S0748-7983(21)00462-5. doi: 10.1016/j.ejso.2021.04.031. Online ahead of print.

ABSTRACT

BACKGROUND: The value of routine surveillance after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear, and expert guidelines offer conflicting recommendations. This study is a systematic review of evidence for surveillance programs.

METHODS: A systematic review of studies evaluating different surveillance methods was undertaken. A meta-analysis was performed for those studies reporting rates of asymptomatic recurrence, treatment of recurrence and overall survival, according to different surveillance methods.

RESULTS: Ten studies were included in the literature review, with five studies appropriate for meta-analysis (1596 patients). Patients within active surveillance programs were more likely to have recurrence detected at an asymptomatic stage (Pooled Rate: 49.3% vs. 19.1%, p = 0.043). Within studies reporting these outcomes, patients with asymptomatic recurrence were more likely to receive treatment for recurrence (Odds Ratio 3.49; 95% CI: 1.73-7.07; p < 0.001) and had longer overall survival (Mean Difference: 9.5 months; 95% CI: 4.1-14.8; p < 0.001) than those with symptoms at time of recurrence.

DISCUSSION: Routine surveillance after surgery for PDAC appears to detect more patients at an asymptomatic stage. Data from these non-randomised trials also suggest that treatment rates and survival may be superior in patients were recurrence is detected when asymptomatic. As such, these data suggest that routine surveillance may improve patient outcomes, although an appropriately conducted trial would be required to address concerns that various sources of bias may be affecting these results.

PMID:34034941 | DOI:10.1016/j.ejso.2021.04.031