Tag: nevin manimala

BMJ Open. 2021 Sep 2;11(9):e049123. doi: 10.1136/bmjopen-2021-049123.

ABSTRACT

OBJECTIVES: Derived neutrophil-to-lymphocytes ratio (dNLR) has recently been reported as a novel potential biomarker associated with prognosis of non-small cell lung cancer (NSCLC). However, evidence for the prognostic utility of dNLR in patients with NSCLC treated with immune checkpoint inhibitors (ICIs) remains inconsistent. The objective of this work was to evaluate the association between pretreatment dNLR and prognosis of patients with NSCLC treated with ICIs.

DESIGN: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

DATA SOURCES: PubMed, EMBASE, Web of Science and the Cochrane Library were searched for eligible studies up to 16 October 2020. ELIGIBILITY CRITERIA: (1) Human subjects receiving ICIs therapy and who had been diagnosed with NSCLC; (2) the baseline values of dNLR were obtained; (3) the objective of the study was to investigate the relationships between dNLR and overall survival (OS) or progression-free survival (PFS) in NSCLC and (4) HR and 95% CI were displayed in the original article or could be extracted from Kaplan-Meier curves.

DATA EXTRACTION AND SYNTHESIS: Two investigators extracted data independently. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with Cochran’s Q test and I² statistics. Publication bias of studies was assessed by Begg’s test and Egger’s test. We used V.12.0 of the Stata statistical software.

RESULTS: This analysis included eight studies (2456 cases) on the prognostic utility of dNLR in ICI therapy for NSCLC. The results indicate that higher dNLR significantly predicted poor OS (HR=1.65, 95% CI 1.46 to 1.88; p<0.001) and PFS (HR=1.38, 95% CI 1.23 to 1.55; p<0.001). Subgroup analyses of OS-related studies indicated that there were similar results in stratifications by ethnicity, sample size, type of HR and dNLR cut-off value. As for PFS-related studies, subgroup analyses showed no significant difference in Asian populations. Publication biases were not detected using Begg’s test and Egger’s linear regression test.

CONCLUSIONS: This meta-analysis indicated that elevated pretreatment dNLR may be a negative prognostic predictor for patients with NSCLC treated with ICIs. More large-sample and higher-quality studies are warranted to support our findings.

PROSPERO REGISTRATION NUMBER: CRD42021214034.

PMID:34475167 | DOI:10.1136/bmjopen-2021-049123

BMJ Open. 2021 Sep 2;11(9):e047142. doi: 10.1136/bmjopen-2020-047142.

ABSTRACT

INTRODUCTION: For over more than a decade, low-dose amitriptyline and mirtazapine are prescribed off-label for insomnia. However, placebo-controlled evidence on these antidepressants for insomnia is still lacking. Therefore, the present trial aims to assess the effectiveness of low-dose amitriptyline (10-20 mg/day) and mirtazapine (7.5-15 mg/day) in patients with insomnia disorder with difficulty maintaining sleep or early-morning awakening problems in general practice.

METHODS AND ANALYSIS: The Drug REdiscovery: low-dose Amitriptyline and Mirtazapine for INsomnia disorder in General practice (DREAMING) study is a randomised, double-blind, placebo-controlled trial in about 50 general practices. Adults (18-85 years) with insomnia disorder (Diagnostic and Statistical Manual of Mental Disorders-5) who ask their general practitioner (GP) for sleep medication when non-pharmacological treatment is deemed not effective, are eligible.

EXCLUSION CRITERIA: isolated sleep initiation problem, contraindications for or drug-drug interactions with either amitriptyline or mirtazapine. Participants (n=156) will be randomly assigned to three parallel treatment groups of 16-week treatment with either amitriptyline (one or two tablets of 10 mg/day) or mirtazapine (one or two tablets of 7.5 mg/day) or placebo (one or two tablets) alongside usual GP care. All participants start and end with single dose, but dose can be doubled following GP consultation in week 3. Questionnaire assessments will be conducted at baseline, week 6, 12, 20 and 52. The primary study outcome is self-reported insomnia severity at 6 weeks, measured with the Insomnia Severity Index (ISI) in an intention to treat analysis. Secondary outcomes include subjective sleep quality quantified by sleep indices, daytime functioning and symptoms, safety and treatment evaluation and other sleep care consumption.

ETHICS AND DISSEMINATION: The Medical Ethics Committee of the VU Medical Centre Amsterdam approved this trial. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders.

TRIAL REGISTRATION NUMBER: NTR7449.

PMID:34475156 | DOI:10.1136/bmjopen-2020-047142

BMJ Open. 2021 Sep 2;11(9):e045239. doi: 10.1136/bmjopen-2020-045239.

ABSTRACT

INTRODUCTION: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients’ own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions.

METHODS AND ANALYSIS: International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm).

ETHICS AND DISSEMINATION: This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator’s site by the Ethics Committee ‘Ethikkommission Nordwest- und Zentralschweiz’ (2020-00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles.

TRIAL REGISTRATION NUMBER: NCT04293146.

PMID:34475143 | DOI:10.1136/bmjopen-2020-045239

BMJ Open. 2021 Sep 2;11(9):e045623. doi: 10.1136/bmjopen-2020-045623.

ABSTRACT

OBJECTIVE: The central aim of this study was to assess the level of psychological problems among college students during school closure due to the emerging COVID-19 pandemic.

DESIGN: Institution-based, cross-sectional study.

SETTING: Colleges in the Amhara regional state of Ethiopia.

PARTICIPANTS: Participants were college students (N=422, >18 years) who were actively enrolled in the selected colleges preceding the survey.

METHODS: Data entry was done using Epi Info V.7.02 and data analysis was done using SPSS V.24.0. Variables with a p value less than 0.25 in the bivariate analysis were entered into the multivariable logistic regression model. Model fitness was checked using the Hosmer-Lemeshow model fitness test. Statistically significant level was declared at p<0.05.

OUTCOME: Level of psychological problem.

RESULTS: This study involved 408 students, with a response rate of 96.6%. In this study, 77.2%, 71.8% and 48.5% of students experienced depression, anxiety and stress-related psychological problems during the lockdown, respectively. The multivariable logistic regression model showed that being female (adjusted OR (AOR)=1.68, 95% CI 1.09 to 2.91), inadequate practice of prevention measures (AOR=1.74, 95% CI 1.01 to 3.02) and living in an urban residency (AOR=0.76, 95% CI 0.48 to 0.94) were independent predictors of psychological problems among students.

CONCLUSIONS: The study revealed that the level of anxiety, stress and depression disorders is optimally high among college students. Therefore, local governments should develop effective psychological interventions for students. Moreover, it is important to consider the educational enrolment type and the academic year of students.

PMID:34475145 | DOI:10.1136/bmjopen-2020-045623

BMJ Glob Health. 2021 Sep;6(Suppl 5):e005411. doi: 10.1136/bmjgh-2021-005411.

ABSTRACT

Phone surveys are a rapid and cost-effective way to collect primary data for research, monitoring and evaluation purposes. But for these data to be precise, reliable and unbiased, women’s perspectives must be accurately represented. Throughout 2020, we conducted seven household surveys in rural India to understand households’ experiences of the COVID-19 pandemic and contemporaneous relief programmes. Given social distancing protocols, we conducted these surveys over the phone, using household phone numbers collected during earlier, face-to-face research. Analysing metadata from these surveys (along with women’s responses to questions about phone use), we determine how gaps in phone access inhibit women’s representation in phone surveys. We find that the prevalence of male management of household phones significantly reduces access to female respondents. This is a problem for two reasons. Firstly, men are usually the first to pick up the phone: in two surveys in which we tracked the gender of the person who picked up, men picked up 63.2% and 71.1% of the time, respectively. Moreover, only a small minority of those we reached by phone were able and willing to pass the phone to a household member of the opposite gender, when prompted (with no statistically significant difference between pass rates for women and men). This low immediate pass rate, in combination with low female pickup, led to fewer women respondents. As such, we recommend that researchers dedicate time and resources to taking appointments and making call-backs to reach more women. We also show that the use of female enumerators improves households’ willingness to participate in women-centred surveys, and call for more investment into female enumerator teams.

PMID:34475116 | DOI:10.1136/bmjgh-2021-005411

BMJ Open. 2021 Sep 2;11(9):e044997. doi: 10.1136/bmjopen-2020-044997.

ABSTRACT

INTRODUCTION: Haemophilia A is a rare bleeding disorder caused by defects in coagulation factor VIII (FVIII). Damoctocog alfa pegol (BAY 94-9027, Jivi, Bayer, Germany) is a site-specifically PEGylated, extended-half-life, recombinant FVIII, approved for use in previously treated patients (PTPs) aged ≥12 years with haemophilia A. However, a real-world evidence regarding routine clinical use of damoctocog alfa pegol is limited.

METHODS AND ANALYSIS: HEM-POWR is a multinational, multicentre, non-interventional, prospective, postmarketing cohort study evaluating the effectiveness and safety of real-world treatment with damoctocog alfa pegol. Estimated enrolment is ≥200 PTPs with haemophilia A, receiving damoctocog alfa pegol (on-demand, prophylaxis or intermittent prophylaxis (as per local label)), observed for 36 months. Primary outcomes are total bleeding events and annualised bleeding rate; secondary outcomes include long-term safety, joint health, pharmacokinetics, patient-reported outcomes (PROs) from validated questionnaires and perioperative haemostasis. Where applicable, reasons for switching to damoctocog alfa pegol, choice of treatment regimen and dose will also be captured. Exploratory and descriptive statistical analyses will be performed, and will be stratified by parameters including, but not limited to, prophylaxis regimen and haemophilia severity. Patients can record bleeds and consumption in electronic (e) Diaries, ePROs, and can access non-promotional study information (videos explaining study procedures) via an online patient portal. Optionally, patients can enrol in the LIFE-ACTIVE substudy designed to investigate the relationship between activity (measured by the ActiGraph CP Insight watch) and effectiveness parameters collected from HEM-POWR.

ETHICS AND DISSEMINATION: Study approval was obtained by local independent ethics committees and authorities in participating study centres across Europe, the Americas and Asia. Informed consent from patients or their legal representative is a requirement for participation. The study results will be submitted for publication in a peer-reviewed scientific journal and presented at scientific conferences.

TRIAL REGISTRATION NUMBERS: NCT03932201, EUPAS26416.

PROTOCOL VERSION AND DATE: V.1.2, 27 September 2019.

PMID:34475142 | DOI:10.1136/bmjopen-2020-044997

Anticancer Res. 2021 Sep;41(9):4629-4636. doi: 10.21873/anticanres.15276.

ABSTRACT

BACKGROUND/AIM: We aimed to develop a novel recurrence prediction model for stage II-III colon cancer using simple auto-artificial intelligence (AI) with improved accuracy compared to conventional statistical models.

PATIENTS AND METHODS: A total of 787 patients who had undergone curative surgery for stage II-III colon cancer between 2000 and 2018 were included. Binomial logistic regression analysis was used to calculate the effect of variables on recurrence. The auto-AI software ‘Prediction One’ (Sony Network Communications Inc.) was used to predict recurrence with the same dataset used for the conventional statical model. Predictive accuracy was assessed by the area under the receiver operating characteristic curve (AUC).

RESULTS: The AUC of the multivariate model was 0.719 (95%CI=0.655-0.784), whereas that of the AI model was 0.815, showing a significant improvement.

CONCLUSION: This auto-AI prediction model demonstrates improved accuracy compared to the conventional model. It could be constructed by clinical surgeons who are not familiar with AI.

PMID:34475091 | DOI:10.21873/anticanres.15276

Anticancer Res. 2021 Sep;41(9):4645-4650. doi: 10.21873/anticanres.15278.

ABSTRACT

BACKGROUND/AIM: Previous reports have indicated that increased expression of Jagged-1 (JAG1) may predict chemotherapy response and poor prognosis for patients with recurrent or metastatic colorectal cancer (CRC). This study aimed to investigate the clinical impact of JAG1 expression level in patients with CRC, including recurrence, especially in those diagnosed with lymph node-positive stage III CRC who underwent complete resection and appropriate adjuvant chemotherapy.

PATIENTS AND METHODS: All patients were enrolled through a retrospective chart review, and only those for whom the clinical course and all clinical information were adequately determined according to the inclusion criteria were selected for retrospective review through medical records. Immunohistochemical staining of JAG1 was performed using paraffin-embedded tissue. JAG1 expression was determined by scoring for staining intensity and percentage of positively stained cells; the final JAG1 score was determined as the sum of both scores.

RESULTS: Sixteen patients who experienced relapse and 15 without (for over 3 years) were selected. The protein expression level of JAG1 showed a tendency for being lower in the group without recurrence, although not statistically significantly (p=0.083); however, the mean JAG1 expression score was significantly lower in the group without recurrence (1.53 vs. 3.19; p=0.004). The patients were divided into two groups with low and high JAG1 expression. The results showed that high JAG1 expression was significantly associated with recurrence of stage III CRC (p=0.029).

CONCLUSION: The expression of JAG1 may be a potential novel biomarker for predicting CRC recurrence.

PMID:34475093 | DOI:10.21873/anticanres.15278

Diabetes Care. 2021 Sep 2:dc211107. doi: 10.2337/dc21-1107. Online ahead of print.

ABSTRACT

OBJECTIVE: Early menopause may be associated with higher cardiovascular disease (CVD) risk. Type 2 diabetes mellitus (T2DM), coupled with early menopause, may result in even greater CVD risk in women. We examined CVD risk in women with early compared with normal-age menopause, with and without T2DM overall, and by race/ethnicity.

RESEARCH DESIGN AND METHODS: We pooled data from the Atherosclerosis Risk in Communities study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. We included women with data on menopausal status, menopausal age, and T2DM, excluding pre- or perimenopausal women and those with prevalent CVD. Outcomes included incident coronary heart disease (CHD), stroke, heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD) (CHD or stroke). We estimated the risk associated with early (<45 years) compared with normal-age menopause using Cox proportional hazards models. Covariates included age, race/ethnicity, education, BMI, blood pressure, cholesterol, smoking, alcohol consumption, antihypertensive medication, lipid-lowering medication, hormone therapy use, and pregnancy history.

RESULTS: We included 9,374 postmenopausal women for a median follow-up of 15 years. We observed 1,068 CHD, 659 stroke, 1,412 HF, and 1,567 ASCVD events. T2DM significantly modified the effect of early menopause on CVD risk. Adjusted hazard ratios for early menopause and the outcomes were greater in women with T2DM versus those without (CHD 1.15 [95% CI 1.00, 1.33] vs. 1.09 [1.03, 1.15]; stroke 1.21 [1.04, 1.40] vs. 1.10 [1.04, 1.16]; ASCVD 1.29 [1.09, 1.51] vs. 1.10 [1.04, 1.17]; HF 1.18 [1.00, 1.39] vs. 1.09 [1.03, 1.16]). The modifying effect of T2DM on the association between early menopause and ASCVD was only statistically significant in Black compared with White women.

CONCLUSIONS: Early menopause was associated with an increased risk for CVD in postmenopausal women. T2DM may further augment the risk, particularly in Black women.

PMID:34475032 | DOI:10.2337/dc21-1107

Stat Med. 2021 Sep 2. doi: 10.1002/sim.9187. Online ahead of print.

ABSTRACT

In this article, we consider the density estimation for data with a mixture structure, where the component densities are assumed unknown, but for each observation, the probabilities of its membership to the subpopulations are known or estimable from other resources. Data of this kind arise from practice and have wide applications. Motivated from the classical kernel density estimation method for a single population, we propose a weighted kernel density estimation method to estimate the component density functions nonparametrically. Within the framework of the EM algorithm, we derive an algorithm that computes our proposed estimates effectively. Via extensive simulation studies, we demonstrate that our methods outperform the existing methods in most occasions. We further compare our methods with existing methods by real data examples.

PMID:34474504 | DOI:10.1002/sim.9187