Category: Nevin Manimala

Proc Natl Acad Sci U S A. 2021 Nov 2;118(44):e2100482118. doi: 10.1073/pnas.2100482118.

ABSTRACT

In this article, we advance divide-and-conquer strategies for solving the community detection problem in networks. We propose two algorithms that perform clustering on several small subgraphs and finally patch the results into a single clustering. The main advantage of these algorithms is that they significantly bring down the computational cost of traditional algorithms, including spectral clustering, semidefinite programs, modularity-based methods, likelihood-based methods, etc., without losing accuracy, and even improving accuracy at times. These algorithms are also, by nature, parallelizable. Since most traditional algorithms are accurate, and the corresponding optimization problems are much simpler in small problems, our divide-and-conquer methods provide an omnibus recipe for scaling traditional algorithms up to large networks. We prove the consistency of these algorithms under various subgraph selection procedures and perform extensive simulations and real-data analysis to understand the advantages of the divide-and-conquer approach in various settings.

PMID:34716259 | DOI:10.1073/pnas.2100482118

Cold Spring Harb Mol Case Stud. 2021 Oct 29:mcs.a006137. doi: 10.1101/mcs.a006137. Online ahead of print.

ABSTRACT

An SLC30A9 associated cerebro renal syndrome was first reported in consanguineous Bedouin kindred by Perez et al in 2017. While the function of the gene has not yet been fully elucidated, it may be implicated in Wnt signaling, nuclear regulation, as well as cell and mitochondrial zinc regulation. In this research report, we present a female proband with two distinct, inherited autosomal recessive loss of function SLC30A9 variants from unrelated parents. To our knowledge, this is the first reported case of a possible SLC30A9 associated cerebro renal syndrome in a nonconsanguineous family. Furthermore, a limited statistical analysis was conducted to identify possible allele frequency differences between populations. Our findings provide further support for an SLC30A9 associated cerebro renal syndrome and may help further clarify the function of this gene.

PMID:34716203 | DOI:10.1101/mcs.a006137

Diabetes Care. 2021 Oct 29:dc202806. doi: 10.2337/dc20-2806. Online ahead of print.

ABSTRACT

OBJECTIVE: Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined. We used cluster analysis machine-learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD.

RESEARCH DESIGN AND METHODS: We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial.

RESULTS: Four distinct phenotypes were identified: cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low BMI; cluster III included women with noncoronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred, respectively, in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (hazard ratio 2.74 [95% CI 2.29-3.29]). Similar phenotypes and outcomes were identified in EXSCEL.

CONCLUSIONS: In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs.

PMID:34716214 | DOI:10.2337/dc20-2806

Heart. 2021 Oct 29:heartjnl-2021-319846. doi: 10.1136/heartjnl-2021-319846. Online ahead of print.

ABSTRACT

BACKGROUND: Diagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic abilities are limited.

OBJECTIVE: The aim was to perform a thorough electrophysiological characterisation of patients with CA and derive an easy-to-use tool for diagnosis.

METHODS: We applied electrocardiographic imaging (ECGI) to acquire electroanatomical maps in patients with CA and controls. A machine learning approach was then used to decipher the complex data sets obtained and generate a surface ECG-based diagnostic tool.

FINDINGS: Areas of low voltage were localised in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualised on the right ventricle. Potential maps revealed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1-V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in the inferior leads II, III and aVF. Respective surface ECG leads showed two characteristic patterns. Ten blinded cardiologists were asked to identify patients with CA by analysing 12-lead ECGs before and after training on the defined ECG patterns. Training led to significant improvements in the detection rate of CA, with an area under the curve of 0.69 before and 0.97 after training.

INTERPRETATION: Using a machine learning approach, an ECG-based tool was developed from detailed electroanatomical mapping of patients with CA. The ECG algorithm is simple and has proven helpful to suspect CA without the aid of advanced imaging modalities.

PMID:34716183 | DOI:10.1136/heartjnl-2021-319846

Clin Cancer Res. 2021 Oct 29:clincanres.2182.2021. doi: 10.1158/1078-0432.CCR-21-2182. Online ahead of print.

ABSTRACT

PURPOSE: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately eight months for metastatic disease. We report results for advanced MpBC treated with ipilimumab+nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013).

METHODS: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity.

RESULTS: Overall, 17 evaluable patients enrolled. Median age was 60 years (26-85); median number of prior therapy lines, 2 (0-5). ORR was 18%; 3/17 patients achieved objective responses (1 complete, 2 partial responses) (2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+ and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AEs), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE); with adrenal insufficiency observed in all three responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1 and absent TILs.

CONCLUSION: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.

PMID:34716198 | DOI:10.1158/1078-0432.CCR-21-2182

BMJ Open. 2021 Oct 29;11(10):e047275. doi: 10.1136/bmjopen-2020-047275.

ABSTRACT

OBJECTIVE: Family caregivers play an essential role in end-of-life care but suffer considerable impact on their own health. A better understanding of main factors related to carers’ health is important to inform interventions. The purpose of the study was to test for the first time the potential impact of a comprehensive set of observable variables on carer health during end-of-life caregiving within a population-based carer sample.

DESIGN: National retrospective, cross-sectional, 4-month post-bereavement postal census survey of family carers of people who died from cancer.

SETTING AND PARTICIPANTS: Relatives who registered a death from cancer during a 2-week period in England were identified from death certificates by the Office of National Statistics; response rate was 1504/5271 (28.5%).

OUTCOME MEASURES: Carers’ mental health was measured through General Health Questionnaire (GHQ)-12; general health was measured through EuroQoL EQ-Visual Analogue Scale (EQ-5D VAS).

METHODS: Survey questions to measure potential variables associated with carer health were based on past research and covered patients’ symptoms and functioning; caregiving activities and hours; informal and formal help received; work hours, other caregiving, volunteering; changes to work, income and expenditure; sleep and relaxation; and demographic variables. Bivariate analyses and ordinary least square regression were performed to investigate these variables’ relationship with outcomes.

RESULTS: Patients’ psychological symptoms and functioning, caregiving hours, female gender and self-sought formal help related to worse mental health. General practitioner and social care input and relaxation related to better mental health. Patients’ psychological symptoms, caregiving hours and female gender were associated with worse general health, and older age, employment and relaxation were associated with better general health.

CONCLUSIONS: Improvements in carers’ health overall may be made by focusing on potential impacts of patients’ psychological symptoms on carers, facilitating respite and relaxation, and paying particular attention to factors affecting female carers.

PMID:34716156 | DOI:10.1136/bmjopen-2020-047275

Inj Prev. 2021 Oct 29:injuryprev-2021-044321. doi: 10.1136/injuryprev-2021-044321. Online ahead of print.

ABSTRACT

OBJECTIVE: Intersection conflict warning systems (ICWSs) have been implemented at high-risk two-way stop-controlled intersections to prevent right-angle crashes and associated injuries. This study involved investigation of the impacts of ICWSs on crash reductions.

METHODS: The study used a quasi-experimental design to analyse the potential causal relations between Minnesota’s ICWSs and various crash rate outcomes (including total, injury, non-injury, targeted right-angle and non-right-angle crashes) in pre-post analyses. A restricted randomisation method enabled identification of three controls to each ICWS treatment intersection, and included as many comparable intersection characteristics as possible. Annual crash rates (per year per intersection) were analysed over the same periods before and after system activation for treatment and control intersections in each matched group. Pre-crash data for 3 years and post-crash data for up to 5 years were included, ranging from 2010 to 2018. Negative binomial regression models with generalised estimating equations were applied to estimate the average, immediate and continuing treatment effects of ICWSs, through the difference-in-differences and difference-in-difference-in-difference approaches, respectively.

RESULTS: The ICWS treatment was significantly associated with a decreasing trend for targeted right-angle crash rates posttreatment. Although not statistically significant, most crash rate outcomes appeared to be elevated immediately after treatment (statistically significant for sideswipe crashes only). Pre-post differences in average crash rates (over entire periods), except for incapacitating injury-related crashes, were not statistically significant between treatment and control intersections.

CONCLUSIONS: The study provided important insight into potential causal associations between intersection safety countermeasures and crashes at high-risk rural two-way stop-controlled intersections.

PMID:34716178 | DOI:10.1136/injuryprev-2021-044321

Am J Pharm Educ. 2021 Oct 29:8766. doi: 10.5688/ajpe8766. Online ahead of print.

ABSTRACT

Objective A virtual educational innovation was designed and implemented to simulate insurance processing for student pharmacists. Objectives of this manuscript are to evaluate the impact of a third party payer simulation on student knowledge and confidence and report student perceptions of the activity.Methods First, second, and third-year pharmacy students at four institutions completed the self-paced simulation. Knowledge was assessed by comparing results of multiple choice questions on the pre- and post-assessments and evaluated by Wilcoxon signed rank test. Confidence was assessed by the change in self-reported confidence scale measurements and compared using Chi-squared test.Results The simulation had a significant impact on student knowledge. The largest improvement was in P1s with a pre- to post-assessment average score difference (scale 0-100) of 16.55 compared to 7.17 for P2s and 10.23 for P3s. The majority of the knowledge questions demonstrated statistically significant improvement, with variation for certain questions between groups. All groups had significantly improved self-rated confidence in their abilities. Most students agreed that they would recommend this activity to other students (91.7%) and it encouraged them to think about the material in a new way (85%).Conclusions Through an innovative simulation on prescription insurance processing, positive results were seen across all 3 levels of learners. Knowledge assessments significantly improved and student confidence increased across all groups and all confidence questions. Participants recommend this activity to other students and felt it was an effective way to learn about insurance adjudication.

PMID:34716136 | DOI:10.5688/ajpe8766

Pediatr Neonatol. 2021 Oct 12:S1875-9572(21)00180-7. doi: 10.1016/j.pedneo.2021.06.020. Online ahead of print.

ABSTRACT

BACKGROUND: Kawasaki disease (KD) is a form of systemic vasculitis that primarily affects children under the age of 5 years old. Antibiotics are often prescribed for KD patients even before a diagnosis is made due to their prolonged fever and elevated inflammatory markers. Therefore, the purpose of this study was to investigate the impact of antibiotics usage on the disease outcome of KD.

METHODS: We carried out a retrospective chart review of children between 2005 and 2017 for initial immunoglobulin (IVIG) treatment of KD. KD children with initial IVIG treatment more than 10 days after the onset of symptoms were excluded.

RESULTS: In total, 280 children were eligible for this study, among which 209 had been treated with antibiotic(s) and 71 had not been. The IVIG resistance rates were 5.6% (4/71), 8.9% (10/112), and 21.6% (21/97) in non-users, single-drug users, and multiple-drug users, respectively (r = 0.205, p = 0.003). The IVIG resistance rate of the multiple antibiotics drug users in KD patients was significantly higher than the other two groups. Furthermore, the likelihood of IVIG resistance was found to increase with elevated C-reactive protein (CRP) values (1.010/unit, p < 0.001) but not with total white blood cell (WBC) count (p = 0.466).

CONCLUSION: The probability of IVIG resistance increases with elevated CRP values and the use of multiple IV antibiotics, thus indicating that physicians should be prudent in administering multiple IV antibiotics when treating assumed infections in KD children.

PMID:34716128 | DOI:10.1016/j.pedneo.2021.06.020

Am J Pharm Educ. 2021 Oct 29:8659. doi: 10.5688/ajpe8659. Online ahead of print.

ABSTRACT

Objective. This study’s principal aim was to assess the moral development of undergraduate pharmacy students and alumni at a university in Jordan.Methods. Using the Professional Ethics in Pharmacy (PEP) test, 512 pharmacy students’ and alumni’s moral reasoning was assessed in a cross-sectional design.Results. The response rate was 49%. The P-score median was 16.7, with no statistical difference observed across all five cohorts. No statistically significant differences in medians P-score between males and females were found (16.7 versus 20, respectively). Also, no statistically significant differences in medians P-scores were observed between students who have completed the ethics course against those who have not completed the ethics course at the time of data collection (median P-score 20 versus 16.7 respectively). No trends in median P-scores were observed, and there were no statistically significant differences in P-scores among the five cohorts.Conclusion. Professional moral reasoning of prospective pharmacists in this study was lower than expected. A further longitudinal study of the cohort, which attempts to correlate moral development with age, sex, education level, and moral education strategy, is warranted.

PMID:34716133 | DOI:10.5688/ajpe8659