Tag: nevin manimala

BMJ Open. 2021 Nov 30;11(11):e049087. doi: 10.1136/bmjopen-2021-049087.

ABSTRACT

OBJECTIVES: We aimed to assess the association between multimorbidity and deprivation on short-term mortality among patients with diffuse large B-cell (DLBCL) and follicular lymphoma (FL) in England.

SETTING: The association of multimorbidity and socioeconomic deprivation on survival among patients diagnosed with DLBCL and FL in England between 2005 and 2013. We linked the English population-based cancer registry with electronic health records databases and estimated adjusted mortality rate ratios by multimorbidity and deprivation status. Using flexible hazard-based regression models, we computed DLBCL and FL standardised mortality risk by deprivation and multimorbidity at 1 year.

RESULTS: Overall, 41 422 patients aged 45-99 years were diagnosed with DLBCL or FL in England during 2005-2015. Most deprived patients with FL with multimorbidities had three times higher hazard of 1-year mortality (HR: 3.3, CI 2.48 to 4.28, p<0.001) than least deprived patients without comorbidity; among DLBCL, there was approximately twice the hazard (HR: 1.9, CI 1.70 to 2.07, p<0.001).

CONCLUSIONS: Multimorbidity, deprivation and their combination are strong and independent predictors of an increased short-term mortality risk among patients with DLBCL and FL in England. Public health measures targeting the reduction of multimorbidity among most deprived patients with DLBCL and FL are needed to reduce the short-term mortality gap.

PMID:34848510 | DOI:10.1136/bmjopen-2021-049087

BMJ Open. 2021 Nov 30;11(11):e054493. doi: 10.1136/bmjopen-2021-054493.

ABSTRACT

INTRODUCTION: In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: ‘What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?’

METHODS AND ANALYSIS: UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years.

ETHICS AND DISSEMINATION: The study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences.

TRIAL REGISTRATION NUMBER: ISRCTN85731188.

PMID:34848524 | DOI:10.1136/bmjopen-2021-054493

BMJ Open. 2021 Nov 30;11(11):e045726. doi: 10.1136/bmjopen-2020-045726.

ABSTRACT

INTRODUCTION: The stigma towards mental disorders can limit the use and effectiveness of available mental health interventions for young people. We aim to systematically review effectiveness of interventions to reduce stigma towards mental disorders in young people, as evidence has not been recently and systematically synthesised on this topic.

METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of randomised or controlled clinical trials of interventions to reduce stigma towards mental disorders in people aged 10-24 years. Studies involving a comparison group, post intervention and/or follow-up assessments of knowledge, attitudes and/or behaviours towards mental disorders (including help-seeking behaviours), will be included. The Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, PubMed and PsycINFO databases will be searched, without time limits, for eligible studies in English or Spanish, and with results available. Databases will be searched from July 2020 to April 2021. The study selection process, the data extraction and the critical evaluation-with the Cochrane risk-of-bias tool-of included studies will be performed independently and in duplicate by teams of reviewers, with the assistance of a third party, until reaching a high degree of agreement. In the presence of substantial heterogeneity (I² >75%), a narrative synthesis of the study results will be used. If feasible, we will also conduct a quality effects model for the statistical synthesis of results. If sufficient data are available, subgroup analyses will be performed to assess potential sources of heterogeneity. Doi plots and the Luis Furuya-Kanamori index will be used to assess publication bias. The Grades of Recommendation, Assessment, Development and Evaluation approach will be used to assess the confidence in the evidence reviewed.

ETHICS AND DISSEMINATION: Results are expected to be published in a peer-reviewed journal in the field of adolescent and/or youth mental health.

PROSPERO REGISTRATION NUMBER: CRD42020210901.

PMID:34848506 | DOI:10.1136/bmjopen-2020-045726

Anticancer Res. 2021 Dec;41(12):6287-6292. doi: 10.21873/anticanres.15450.

ABSTRACT

BACKGROUND/AIM: To retrospectively analyze the results of histoculture drug response assays (HDRAs) to determine whether the results could predict platinum sensitivity and prognosis in ovarian cancer.

PATIENTS AND METHODS: One hundred thirty-nine patients with ovarian cancer were reviewed. HDRAs were conducted for platinum and taxane agents. Platinum resistance and sensitivity occurred in 21 and 118 patients, respectively. To analyze the relationship between the inhibition rates (IRs) of tumor growth caused by the platinum agent and clinical outcomes, Student’s t-test and linear regression analysis were used.

RESULTS: We found that the average IRs of the platinum and taxane agent were not statistically significant between the platinum-sensitive and – resistant groups. There was no statistical significance for overall survival, progression-free survival, or platinum-free interval.

CONCLUSION: The HDRA is not useful for predicting platinum sensitivity and survival outcomes.

PMID:34848485 | DOI:10.21873/anticanres.15450

BMJ Open. 2021 Nov 30;11(11):e043242. doi: 10.1136/bmjopen-2020-043242.

ABSTRACT

OBJECTIVE: Typically, migraine prevention trials focus on reducing migraine days. This narrow focus may not capture all that is important to people with migraine. Inconsistency in outcome selection across trials limits the potential for data pooling and evidence synthesis. In response, we describe the development of core outcome set for migraine (COSMIG).

DESIGN: A two-stage approach sought to achieve international, multistakeholder consensus on both the core domain set and core measurement set. Following construction of a comprehensive list of outcomes, expert panellists (patients, healthcare professionals and researchers) completed a three-round electronic-Delphi study to support a reduction and prioritisation of core domains and outcomes. Participants in a consensus meeting finalised the core domains and methods of assessment. All stages were overseen by an international core team, including patient research partners.

RESULTS: There was a good representation of patients (episodic migraine (n=34) and chronic migraine (n=42)) and healthcare professionals (n=33) with high response and retention rates. The initial list of domains and outcomes was reduced from >50 to 7 core domains for consideration in the consensus meeting, during which a 2-domain core outcome set was agreed.

CONCLUSION: International and multistakeholder consensus emerged to describe a two-domain core outcome set for reporting research on preventive interventions for chronic and episodic migraine: migraine-specific pain and migraine-specific quality of life. Intensity of migraine pain assessed with an 11-point Numerical Rating Scale and the frequency as the number of headache/migraine days over a specified time period. Migraine-specific quality of life assessed using the Migraine Functional Impact Questionnaire.

PMID:34848505 | DOI:10.1136/bmjopen-2020-043242

Anticancer Res. 2021 Dec;41(12):5959-5971. doi: 10.21873/anticanres.15415.

ABSTRACT

BACKGROUND/AIM: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs).

MATERIALS AND METHODS: Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKCλ on trypan blue staining and tumor-sphere formation by ALDH1^high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined.

RESULTS: GLO 1^high, PKCλ^high, and ALDH1A3^high tumors were enriched in stage I/II/III/IV samples, associated with the HER2 and TNBC subtypes according to receptor status, and associated with the HER2-enriched and basal-like subtypes according to PAM50. Inhibition of either GLO 1 (TLSC702) or PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1^high cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1^high cells.

CONCLUSION: GLO 1 and PKCλ are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.

PMID:34848450 | DOI:10.21873/anticanres.15415

Anticancer Res. 2021 Dec;41(12):6267-6272. doi: 10.21873/anticanres.15447.

ABSTRACT

BACKGROUND/AIM: Treatments containing ipilimumab have shown a good outcome in patients with non-small cell lung cancer (NSCLC) regardless of the PD-L1 tumor proportion score (TPS). However, the association between PD-L1 TPS and the expression of CTLA-4 in tumor-infiltrating lymphocytes is unknown.

PATIENTS AND METHODS: Fifty-five NSCLC patients who underwent surgery in our hospital were included in this study. We measured the proportions of CTLA-4⁺ regulatory T cells, and CTLA-4⁺ CD8 T cells, and statistically analyzed their correlations with the PD-L1 TPS.

RESULTS: Statistical correlations were found neither between the proportion of CTLA-4⁺ regulatory T cells to CD8 T cells and the PD-L1 TPS (p=0.2859) nor between the proportion of CTLA-4⁺ cells in CD8 T cells and the PD-L1 TPS (p=0.1919).

CONCLUSION: The proportions of CTLA-4⁺ regulatory T cells to CD8 T cells and CTLA-4⁺ cells in CD8 T cells were irrelevant to the PD-L1 TPS in NSCLC patients.

PMID:34848482 | DOI:10.21873/anticanres.15447

J Obstet Gynaecol Can. 2021 Nov 27:S1701-2163(21)00835-5. doi: 10.1016/j.jogc.2021.11.009. Online ahead of print.

ABSTRACT

A quality assurance study was completed following the implementation of a standardized opioid prescribing and education protocol post cesarean delivery. The primary goal was to determine the need for a policy on postpartum opioid prescribing practices and whether the protocol worked. There was a decrease in the number of tablets provided post intervention and no statistically significant maternal or neonatal readmissions for suspected opioid toxicity or pain control. Combination prescribing of Tylenol 3 and/or tramadol and another opioid occurred in both groups. Our results show a need for concise guidelines regarding opioid prescribing following cesarean delivery.

PMID:34848352 | DOI:10.1016/j.jogc.2021.11.009

J Allergy Clin Immunol Pract. 2021 Nov 27:S2213-2198(21)01295-2. doi: 10.1016/j.jaip.2021.11.017. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-μg peanut protein (Viaskin™ Peanut 250 μg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children.

OBJECTIVE: To examine the safety of VP250 in children, using a study design approximating potential real-world use.

METHODS: REALISE is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported.

RESULTS: Three hundred ninety-three children were randomized 3:1 to receive VP250 (n=294) or placebo (n=99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued due to adverse events. Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall adverse event rates were similar among participants with and without history of peanut anaphylaxis.

CONCLUSIONS: In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

PMID:34848381 | DOI:10.1016/j.jaip.2021.11.017

Neuroimage. 2021 Nov 27:118751. doi: 10.1016/j.neuroimage.2021.118751. Online ahead of print.

ABSTRACT

BACKGROUND: Large-scale longitudinal and multi-centre studies are used to explore neuroimaging markers of normal aging, and neurodegenerative and mental health disorders. Longitudinal changes in brain structure are typically small, therefore the reliability of automated techniques is crucial. Determining the effects of different factors on reliability allows investigators to control those adversely affecting reliability, calculate statistical power, or even avoid particular brain measures with low reliability. This study examined the impact of several image acquisition and processing factors and documented the test-retest reliability of structural MRI measurements.

METHODS: In Phase I, 20 healthy adults (11 females; aged 20-30 years) were scanned on two occasions three weeks apart on the same scanner using the ADNI-3 protocol. On each occasion, individuals were scanned twice (repetition), after re-entering the scanner (reposition) and after tilting their head forward. At one year follow-up, nine returning individuals and 11 new volunteers were recruited for Phase II (11 females; aged 22-31 years). Scans were acquired on two different scanners using the ADNI-2 and ADNI-3 protocols. Structural images were processed using FreeSurfer (v5.3.0, 6.0.0 and 7.1.0) to provide subcortical and cortical volume, cortical surface area and thickness measurements. Intra-class correlation coefficients (ICC) were calculated to estimate test-retest reliability. We examined the effect of repetition, reposition, head tilt, time between scans, MRI sequence and scanner on reliability of structural brain measurements. Mean percentage differences were also calculated in supplementary analyses.

RESULTS: Using the FreeSurfer v7.1.0 longitudinal pipeline, we observed high reliability for subcortical and cortical volumes, and cortical surface areas at repetition, reposition, three weeks and one year (mean ICCs>0.97). Cortical thickness reliability was lower (mean ICCs>0.82). Head tilt had the greatest adverse impact on ICC estimates, for example reducing mean right cortical thickness to ICC=0.74. In contrast, changes in ADNI sequence or MRI scanner had a minimal effect. We observed an increase in reliability for updated FreeSurfer versions, with the longitudinal pipeline consistently having a higher reliability than the cross-sectional pipeline.

DISCUSSION: Longitudinal studies should monitor or control head tilt to maximise reliability. We provided the ICC estimates and mean percentage differences for all FreeSurfer brain regions, which may inform power analyses for clinical studies and have implications for the design of future longitudinal studies.

PMID:34848299 | DOI:10.1016/j.neuroimage.2021.118751