Nevin Manimala

Cancer Med. 2021 Jun 21. doi: 10.1002/cam4.4072. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop a new interface for the widely used prognostic breast cancer tool: Predict: Breast Cancer. To facilitate decision-making around post-surgery breast cancer treatments. To derive recommendations for communicating the outputs of prognostic models to patients and their clinicians.

METHOD: We employed a user-centred design process comprised of background research and iterative testing of prototypes with clinicians and patients. Methods included surveys, focus groups and usability testing.

RESULTS: The updated interface now caters to the needs of a wider audience through the addition of new visualisations, instantaneous updating of results, enhanced explanatory information and the addition of new predictors and outputs. A programme of future research was identified and is now underway, including the provision of quantitative data on the adverse effects of adjuvant breast cancer treatments. Based on our user-centred design process, we identify six recommendations for communicating the outputs of prognostic models including the need to contextualise statistics, identify and address gaps in knowledge, and the critical importance of engaging with prospective users when designing communications.

CONCLUSIONS: For prognostic algorithms to fulfil their potential to assist with decision-making they need carefully designed interfaces. User-centred design puts patients and clinicians needs at the forefront, allowing them to derive the maximum benefit from prognostic models.

PMID:34152085 | DOI:10.1002/cam4.4072

J Magn Reson Imaging. 2021 Jun 21. doi: 10.1002/jmri.27791. Online ahead of print.

ABSTRACT

BACKGROUND: Congenital shunt location is related to Eisenmenger syndrome (ES) survival. Moreover, right ventricular (RV) remodeling is associated with poor survival in pulmonary hypertension.

PURPOSE: To investigate RV remodeling using comprehensive magnetic resonance imaging (MRI) techniques and identify its relationship with prognosis in ES subgroups classified by shunt location.

STUDY TYPE: Prospective observational study.

POPULATION: Fifty-four adults with ES (16 with pre-tricuspid shunt and 38 with post-tricuspid shunt).

FIELD STRENGTH/SEQUENCE: 3.0 T/cine MRI with balanced steady-state free precession sequence, late gadolinium enhancement with inversion recovery segmented gradient echo sequence and phase-sensitive reconstruction, and T1 mapping with modified Look-Locker inversion recovery sequence.

ASSESSMENT: Demographics, clinical characteristics, hemodynamics, RV remodeling features (morphology, systolic function, RV-pulmonary artery (PA) coupling and myocardial fibrosis), and prognosis were compared between ES subgroups. The adverse endpoint was all-cause mortality or readmission for heart failure.

STATISTICAL TESTS: The independent samples t-test, Fisher’s exact test or Chi-squared test, and the Kaplan-Meier method were used. P < 0.05 was considered significant.

RESULTS: Compared to patients with post-tricuspid shunt, patients with pre-tricuspid shunt were significantly older and had higher N-terminal pro-B-type natriuretic peptide concentrations and poorer exercise tolerance. Pre-tricuspid shunt showed significantly larger RV dimensions (end-diastolic volume index: 185.81 ± 37.49 vs. 98.20 ± 36.26 mL/m² ), worse RV ejection fraction (23.54% ± 12.35% vs. 40.82% ± 10.77%), and RV-PA decoupling (0.35 ± 0.31 vs. 0.72 ± 0.29). Biventricular myocardial fibrosis was significantly more severe in pre-tricuspid shunt than post-tricuspid shunt (extracellular volume, left ventricle: 35.85% ± 2.58% vs. 29.10% ± 5.20%; RV free wall: 30.93% ± 5.65% vs. 26.75% ± 5.15%). In addition, pre-tricuspid shunt demonstrated a significantly increased risk of adverse endpoint (hazard ratio: 2.938, 95% confidence interval: 1.204-7.172).

DATA CONCLUSION: ES with pre-tricuspid shunt might be a unique subtype with worse clinically decompensated RV remodeling and poor prognosis.

LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 5.

PMID:34152058 | DOI:10.1002/jmri.27791

J Sleep Res. 2021 Jun 21:e13430. doi: 10.1111/jsr.13430. Online ahead of print.

ABSTRACT

An impairment in next day driving performance has been reported for almost every drug currently United States Food and Drug Administration (FDA) approved for improvement of sleep in chronic and transient insomnia. Tasimelteon, a melatonin receptor agonist, demonstrated significant improvements in night-time sleep, daytime naps, and sleep timing in non-24-hr sleep-wake disorder (Non-24) by entraining these patients to a 24-hr day as measured by melatonin and cortisol rhythms. Given this new mechanism of action of entraining the biological clock, we conducted a study to evaluate the potential effect tasimelteon may have on the ability to operate a motor vehicle. The study was conducted in 48 healthy adult subjects using a randomised, double-blind, placebo and active (zopiclone 7.5 mg) controlled study with a 3-period cross-over design. Driving performance was assessed by measuring standard deviation of lateral position (SDLP) using the validated Cognitive Research Corporation Driving Simulator-MiniSim. The difference in least square mean SDLP for tasimelteon was 1.22 cm reflecting a non-significant increase in SDLP change from placebo (p = .1119). In contrast, treatment with the active control, zopiclone 7.5 mg, was associated with a meaningful and significant increase in SDLP, change from placebo for zopiclone was 4.14 cm (p < .0001). The lack of clinically meaningful and statistically significant finding with tasimelteon was further supported by the symmetry analysis, which showed the distribution of within-subject differences between tasimelteon and placebo was symmetric about zero. At the FDA-approved 20 mg dose to treat Non-24, tasimelteon did not impair next-day driving performance compared to placebo in adult healthy volunteers.

PMID:34152055 | DOI:10.1111/jsr.13430

Int J Cancer. 2021 Jun 21. doi: 10.1002/ijc.33714. Online ahead of print.

ABSTRACT

The proposed different origins and pathways to of the dualistic model of Epithelial Ovarian Cancer (EOC) may affect and alter the potential risk reduction related to hysterectomy, salpingectomy and tubal ligation. The aim of this study was to analyze associations between hysterectomy, salpingectomy or tubal ligation and risk reduction of EOC Type I and II. In this nationwide register-based case-control study, women diagnosed with EOC, Fallopian tube or primary peritoneal cancer between 2008 and 2014 were included. Cases were classified into Type I and II according to histology and predefined criteria. The exposure variables; hysterectomy, salpingectomy and tubal ligation were identified from national registries. Conditional logistic regression analyses were performed to evaluate associations between Type I and II EOC and the exposure variables. Among 4669 registered cases, 4040 were eligible and assessed for subtyping resulting in 1033 Type I and 3007 Type II. Ten controls were randomly assigned to each case from the register of population. In regression analyses, women with previous salpingectomy had a significantly lower risk of EOC Type II (OR 0.62; 95%CI 0.45-0.85) but not Type I (OR 1.16; 95%CI 0.75-1.78). Hysterectomy was associated with a reduced risk of both EOC Type I (OR 0.71, 95%CI 0.52-0.99) and Type II (OR 0.81, 95%CI 0.68-0.96). Similar estimates were obtained for tubal ligation, although without statistical significance. The association between salpingectomy and reduced risk of EOC Type II supports the proposed theory of high grade serous cancer originating from the tubal fimbriae. This article is protected by copyright. All rights reserved.

PMID:34152012 | DOI:10.1002/ijc.33714

J Am Med Inform Assoc. 2021 Jun 21:ocab087. doi: 10.1093/jamia/ocab087. Online ahead of print.

ABSTRACT

OBJECTIVE: In electronic health record data, the exact time stamp of major health events, defined by significant physiologic or treatment changes, is often missing. We developed and externally validated a method that can accurately estimate these time stamps based on accurate time stamps of related data elements.

MATERIALS AND METHODS: A novel convolution-based change detection methodology was developed and tested using data from the national deidentified clinical claims OptumLabs data warehouse, then externally validated on a single center dataset derived from the M Health Fairview system.

RESULTS: We applied the methodology to estimate time to liver transplantation for waitlisted candidates. The median error between estimated date within the period of the actual true date was zero days, and median error was 92% and 84% of the transplants, in development and validation samples, respectively.

DISCUSSION: The proposed method can accurately estimate missing time stamps. Successful external validation suggests that the proposed method does not need to be refit to each health system; thus, it can be applied even when training data at the health system is insufficient or unavailable. The proposed method was applied to liver transplantation but can be more generally applied to any missing event that is accompanied by multiple related events that have accurate time stamps.

CONCLUSION: Missing time stamps in electronic healthcare record data can be estimated using time stamps of related events. Since the model was developed on a nationally representative dataset, it could be successfully transferred to a local health system without substantial loss of accuracy.

PMID:34151985 | DOI:10.1093/jamia/ocab087

Int J Epidemiol. 2021 Jun 21:dyab108. doi: 10.1093/ije/dyab108. Online ahead of print.

ABSTRACT

BACKGROUND: With reduced community mobility, household infections may become increasingly important in SARS-CoV-2 transmission dynamics.

METHODS: We investigate the intra-household transmission of COVID-19 through the secondary-attack rate (SAR) and household reproduction number (Rh). We estimate these using (i) data from 29 prior studies (February-August 2020), (ii) epidemiologically linked confirmed cases from Singapore (January-April 2020) and (iii) widespread-testing data from Vo’ (February-March 2020). For (i), we use a Bayesian random-effects model that corrects for reverse transcription-polymerase chain reaction (RT-PCR) test sensitivity and asymptomatic cases. We investigate the robustness of Rh with respect to community transmission rates and mobility patterns.

RESULTS: The corrected pooled estimates from prior studies for SAR and Rh are 24% (20-28%) and 0.34 (0.30-0.38), respectively. Without corrections, the pooled estimates are: SAR = 18% (14-21%) and Rh = 0.28 (0.25-0.32). The corrected estimates line up with direct estimates from contact-tracing data from Singapore [Rh = 0.32 (0.22-0.42)] and population testing data from Vo’ [SAR = 31% (28-34%) and Rh = 0.37 (0.34-0.40)]. The analysis of Singapore data further suggests that the value of Rh (0.22-0.42) is robust to community-spread dynamics; our estimate of Rh stays constant whereas the fraction of infections attributable to household transmission (Rh/Reff) is lowest during outbreaks (5-7%) and highest during lockdowns and periods of low community spread (25-30%).

CONCLUSIONS: The three data-source types yield broadly consistent estimates for SAR and Rh. Our study suggests that household infections are responsible for a large fraction of infections and so household transmission may be an effective target for intervention.

PMID:34151970 | DOI:10.1093/ije/dyab108

J Am Med Inform Assoc. 2021 Jun 21:ocab075. doi: 10.1093/jamia/ocab075. Online ahead of print.

ABSTRACT

OBJECTIVE: As master of science in health informatics (MSc HI) programs emerge in developing countries, quality assurance of these programs is essential. This article describes a comprehensive comparative analysis of competencies covered by accredited MSc HI programs in the East African common labor and educational zone.

MATERIALS AND METHODS: Two reviewers independently reviewed curricula from 7 of 8 accredited MSc HI university programs. The reviewers extracted covered competencies, coding these based on a template that contained 73 competencies derived from competencies recommended by the International Medical Informatics Association, plus additional unique competencies contained within the MSc HI programs. Descriptive statistics were used to summarize the structure and completion requirements of each MSc HI program. Jaccard similarity coefficient was used to compare similarities in competency coverage between universities.

RESULTS: The total number of courses within the MSc HI degree programs ranged from 8 to 22, with 35 to 180 credit hours. Cohen’s kappa for coding competencies was 0.738. The difference in competency coverage was statistically significant across the 7 institutions (P = .012), with covered competencies across institutions ranging from 32 (43.8%) to 49 (67.1%) of 73. Only 4 (19%) of 21 university pairs met a cutoff of over 70% similarity in shared competencies.

DISCUSSION: Significant variations observed in competency coverage within MSc HI degree programs could limit mobility of student, faculty, and labor.

CONCLUSIONS: Comparative analysis of MSc HI degree programs across 7 universities in East Africa revealed significant differences in the competencies that were covered.

PMID:34151967 | DOI:10.1093/jamia/ocab075

J Am Med Inform Assoc. 2021 Jun 21:ocab101. doi: 10.1093/jamia/ocab101. Online ahead of print.

ABSTRACT

OBJECTIVE: Multitask learning (MTL) using electronic health records allows concurrent prediction of multiple endpoints. MTL has shown promise in improving model performance and training efficiency; however, it often suffers from negative transfer – impaired learning if tasks are not appropriately selected. We introduce a sequential subnetwork routing (SeqSNR) architecture that uses soft parameter sharing to find related tasks and encourage cross-learning between them.

MATERIALS AND METHODS: Using the MIMIC-III (Medical Information Mart for Intensive Care-III) dataset, we train deep neural network models to predict the onset of 6 endpoints including specific organ dysfunctions and general clinical outcomes: acute kidney injury, continuous renal replacement therapy, mechanical ventilation, vasoactive medications, mortality, and length of stay. We compare single-task (ST) models with naive multitask and SeqSNR in terms of discriminative performance and label efficiency.

RESULTS: SeqSNR showed a modest yet statistically significant performance boost across 4 of 6 tasks compared with ST and naive multitasking. When the size of the training dataset was reduced for a given task (label efficiency), SeqSNR outperformed ST for all cases showing an average area under the precision-recall curve boost of 2.1%, 2.9%, and 2.1% for tasks using 1%, 5%, and 10% of labels, respectively.

CONCLUSIONS: The SeqSNR architecture shows superior label efficiency compared with ST and naive multitasking, suggesting utility in scenarios in which endpoint labels are difficult to ascertain.

PMID:34151965 | DOI:10.1093/jamia/ocab101

J Antimicrob Chemother. 2021 Jun 21:dkab204. doi: 10.1093/jac/dkab204. Online ahead of print.

ABSTRACT

BACKGROUND: Clostridioides difficile infection (CDI) is a healthcare-acquired infection (HAI) causing significant morbidity and mortality. Welsh CDI rates are high in comparison with those in England and Scotland.

OBJECTIVES: This retrospective ecological study used aggregated disease surveillance data to understand the impact of total and high-risk Welsh GP antibiotic prescribing on total and stratified inpatient/non-inpatient CDI incidence.

METHODS: All cases of confirmed CDI, during the financial years 2014-15 to 2017-18, were linked to aggregated rates of antibiotic prescribing in their GP surgery and classified as ‘inpatient’, ‘non-inpatient’ or ‘unknown’ by Public Health Wales. Multivariable negative-binomial regression models, comparing CDI incidence with antibiotic prescribing rates, were adjusted for potential confounders: location; age; social deprivation; comorbidities (estimated from prevalence of key health indicators) and proton pump inhibitor (PPI) prescription rates.

RESULTS: There were 4613 confirmed CDI cases, with an incidence (95% CI) of 1.44 (1.40-1.48) per 1000 registered patients. Unadjusted analysis showed that an increased risk of total CDI incidence was associated with higher total antibiotic prescribing [relative risk (RR) (95% CI) = 1.338 (1.170-1.529) per 1000 items per 1000 specific therapeutic group age-sex related GP prescribing units (STAR-PU)] and that high-risk antibiotic classes were positively associated with total CDI incidence. Location, age ≥65 years and diabetes were associated with increased risk of CDI. After adjusting for confounders, prescribing of clindamycin showed a positive association with total CDI incidence [RR (95% CI) = 1.079 (1.001-1.162) log items per 1000 registered patients].

CONCLUSIONS: An increased risk of CDI is demonstrated at a primary care practice population level, reflecting their antibiotic prescribing rates, particularly clindamycin, and population demographics.

PMID:34151964 | DOI:10.1093/jac/dkab204

Eur J Cardiothorac Surg. 2021 Jun 21:ezab161. doi: 10.1093/ejcts/ezab161. Online ahead of print.

ABSTRACT

OBJECTIVES: This analysis aimed to compare both short- and long-term outcomes of hybrid coronary revascularization (HCR) with different techniques and coronary artery bypass grafting (CABG).

METHODS: Twenty-three studies were included, covering 10 468 different patients, among whom 2403 patients underwent HCR with either simultaneous or staged method and 8065 patients underwent CABG.

RESULTS: Compared with CABG, HCR had a statistically significant lower risk of stroke [odds ratio (OR) = 0.55, P = 0.049], major adverse cardiac and cerebrovascular events (OR = 0.69, P = 0.024) and blood transfusion (BT) (OR = 0.39, P < 0.001), whereas no significant differences were detected in mortality, myocardial infarction and repeat revascularization. A network meta-analysis showed that simultaneous HCR had significantly better outcomes in stroke (OR = 0.24, P = 0.01) and major adverse cardiac and cerebrovascular events (OR = 0.29, P < 0.001), and staged HCR had a significantly better outcome in BT (OR = 0.31, P < 0.001). According to the frequentist statistic results, simultaneous HCR had the highest probability of being the best treatment in terms of mortality (84%), stroke (97%), myocardial infarction (88%) and major adverse cardiac and cerebrovascular events (99%), whereas staged HCR had the highest probability of being the best in postoperative repeat revascularization (59%) and BT (83%). However, long-term results showed no significant difference between the HCR and CABG techniques.

CONCLUSIONS: HCR appears to be a feasible option for multivessel coronary artery disease patients. Compared to traditional CABG, HCR had lower risk of adverse events in the short term, but in the long term, survival rate and freedom from major adverse cardiac and cerebrovascular events rate were similar between groups.

PMID:34151954 | DOI:10.1093/ejcts/ezab161