Nevin Manimala

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):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

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

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

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

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

Korean J Med Educ. 2021 Sep;33(3):191-201. doi: 10.3946/kjme.2021.199. Epub 2021 Aug 27.

ABSTRACT

PURPOSE: This study aims to design that using formative assessment as an instructional strategy in real-time online classes, and to explore the application of Bloom’s taxonomy in the development of formative assessment items.

METHODS: We designed the instruction using formative assessment in real-time online classes, developed the items of formative assessment, analyzed the items statistically, and investigated students’ perceptions of formative assessment through a survey.

RESULTS: It is designed to consist of 2-3 learning outcomes per hour of class and to conduct the formative assessment with 1-2 items after the lecture for each learning outcome. Formative assessment was 31 times in the physiology classes (total 48 hours) of three basic medicine integrated. There were nine “knowledge” items, 40 “comprehension” items, and 55 “application” items. There were 33 items (31.7%) with a correct rate of 80% or higher, which the instructor thought was appropriate. As a result of the survey on students’ perceptions of formative assessment, they answered that it was able to concentrate on the class and that it was helpful in achieving learning outcomes.

CONCLUSION: The students focused during class because they had to take formative assessment immediately after the learning outcome lecture. “Integration of lesson and assessments” was maximized by solving the assessment items as well as through the instructor’s immediate explanation of answers. Through formative assessment, the students were able to utilize metacognition by learning what content they understood or did not understand. Items that consider Bloom’s taxonomy allow students to remember, understand, and apply to clinical contexts.

PMID:34474526 | DOI:10.3946/kjme.2021.199

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

Stat Med. 2021 Sep 2. doi: 10.1002/sim.9184. Online ahead of print.

ABSTRACT

Current status data arise when each subject is observed only once and the failure time of interest is only known to be either smaller or larger than the observation time rather than observed exactly. For the situation, due to the use of imperfect diagnostic tests, the failure status could often suffer misclassification or one observes misclassified data, which may result in severely biased estimation if not taken into account. In this article, we discuss regression analysis of such misclassified current status data arising from the additive hazards model, and a simulation-extrapolation (SIMEX) approach is developed for the estimation. Furthermore, the asymptotic properties of the proposed estimators are established, and a simulation study is conducted to assess the empirical performance of the method, which indicates that the proposed procedure performs well. In particular, it can correct the estimation bias given by the naive method that ignores the existence of misclassification. An application to a medical study on gonorrhea is also provided.

PMID:34474502 | DOI:10.1002/sim.9184

Stat Med. 2021 Sep 2. doi: 10.1002/sim.9185. Online ahead of print.

ABSTRACT

The potential benefit of using a surrogate marker in place of a long-term primary outcome is very attractive in terms of the impact on study length and cost. Many available methods for quantifying the effectiveness of a surrogate endpoint either rely on strict parametric modeling assumptions or require that the primary outcome and surrogate marker are fully observed that is, not subject to censoring. Moreover, available methods for quantifying surrogacy typically provide a proportion of treatment effect explained (PTE) measure and do not directly address the important questions of whether and how the trial can be ended earlier using the surrogate marker. In this article, we specifically address these important questions by proposing a PTE measure to quantify the feasibility of ending trials early based on endpoint information collected at an earlier landmark point $t_0$ in a time-to-event outcome setting. We provide a framework for deriving an optimally predicted outcome for individual patients at $t_0$ based on a combination of surrogate marker and event time information in the presence of censoring. We propose a non-parametric estimator for the PTE measure and derive the asymptotic properties of our estimators. Finite sample performance of our estimators are illustrated via extensive simulation studies and a real data application examining the potential of hemoglobin A1c and fasting plasma glucose to predict treatment effects on long term diabetes risk based on the Diabetes Prevention Program study.

PMID:34474500 | DOI:10.1002/sim.9185