Category: Statistics

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

Prim Care Diabetes. 2021 Oct 26:S1751-9918(21)00186-8. doi: 10.1016/j.pcd.2021.10.002. Online ahead of print.

ABSTRACT

AIM: To establish two scoring models for identifying individuals at risk of developing Impaired Glucose Metabolism (IGM) or Type two Diabetes Mellitus (T2DM) in Qatari.

MATERIALS AND METHODS: A sample of 2000 individuals, from Qatar BioBank, was evaluated to determine features predictive of T2DM and IGM. Another sample of 1000 participants was obtained for external validation of the models. Several scoring models screening for T2DM were evaluated and compared to the model proposed by this study.

RESULTS: Age, gender, waist-to-hip-ratio, history of hypertension and hyperlipidemia, and levels of educational were statistically associated with the risk of T2DM and constituted the Qatar diabetes mellitus risk score (QDMRISK). Along with, the 6 aforementioned variables, the IGM model showed that BMI was statistically significant. The QDMRISK performed well with area under the curve (AUC) 0.870 and .815 in the development and external validation cohorts, respectively. The QDMRISK showed overall better accuracy and calibration compared to other evaluated scores. The IGM model showed good accuracy and calibration, with AUCs .796 and .774 in the development and external validation cohorts, respectively.

CONCLUSIONS: This study developed Qatari-specific diabetes and IGM risk scores to identify high risk individuals and can guide the development of a nationwide primary prevention program.

PMID:34716113 | DOI:10.1016/j.pcd.2021.10.002

J Geriatr Oncol. 2021 Oct 26:S1879-4068(21)00239-3. doi: 10.1016/j.jgo.2021.10.007. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the toxicity patterns and effectiveness of doublet chemotherapy when administered at reduced doses of 20% (FOLFOX or FOLFIRI) in combination with anti-EGFR antibodies (cetuximab or panitumumab) in old, vulnerable patients with metastatic colorectal cancer (mCRC).

PATIENTS AND METHODS: We performed a retrospective observational study of RAS and BRAF wild-type, vulnerable patients aged ≥70 years with previously untreated mCRC. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).

RESULTS: One hundred and eighteen patients were collected from 14 selected Italian centres. The median age was 75 (range, 70-85). Geriatric screening by G8 tool gave a score ≤ 14 in all patients. In total, 75 and 43 patients received FOLFOX or FOLFIRI, respectively, in combination with panitumumab (53%) or cetuximab (47%). The overall incidence of grade (G) 3-4 neutropenia was 11.8%, and for skin rash 11%. The most frequent adverse events were G1-2 skin rash (49.1%), G1-2 diarrhea (21.1%) and G1-2 nausea (17.7%). The ORR was 57.3%. Stable disease was observed in 29.1% of patients, with a disease control rate of 86.4%. With a median follow-up of 18 months, the median PFS was 10.0 months (95% confidence interval [CI]: 8.5-11.4), while the median OS was 18.0 months (95% CI: 16.0-19.9). No statistically significant difference was observed between the regimens in terms of ORR, PFS (p = 0.908), and OS (p = 0.832).

CONCLUSION: This study shows that with an appropriate design, including reduced doses, vulnerable older patients best tolerate chemotherapy when combined with anti-EGFR antibodies.

PMID:34716122 | DOI:10.1016/j.jgo.2021.10.007

Int Orthod. 2021 Oct 26:S1761-7227(21)00125-X. doi: 10.1016/j.ortho.2021.10.002. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to determine the effects of alveolar decortications (AD) closer and farther from the tooth on Orthodontic tooth movement (OTM) and root resorption.

MATERIALS AND METHODS: Twenty-four Wistar rats (age 17 weeks) were used in the study. Three groups were formed by randomly dividing the rats into: 1) Control Group (N=8): OTM (14 days) without any surgical insult; 2) Near Group (N=8) OTM (14 days)+Alveolar Decortications (AD) adjacent to roots of the maxillary first molar; 3) Far Group (N=8) OTM (14 days)+AD 5mm away from the roots of the maxillary first molar. OTM was performed using a closed coil Nickel-Titanium (NiTi) spring to apply a mesial force on maxillary first molars of 8-10 grams. AD was performed with high-speed quarter round bur on the palatal aspect of alveolar bone. The rats were euthanized after 2 weeks of OTM and microfocus computed tomography and histological analysis were performed.

RESULTS: Near-AD and Far-AD groups exhibited significantly increased OTM and reduction of Bone volume fraction compared to control. The root volume was significantly decreased (increased root resorption) in the Near-AD group. Histological analysis showed no statistically significant difference between the groups.

CONCLUSIONS: Alveolar decortications lead to a significant increase in the rate of OTM. Increased root resorption was observed when the alveolar decortications were performed close to the maxillary molar.

PMID:34716100 | DOI:10.1016/j.ortho.2021.10.002

Stat Appl Genet Mol Biol. 2021 Oct 29. doi: 10.1515/sagmb-2021-0047. Online ahead of print.

ABSTRACT

The human gut microbiome has been shown to be associated with a variety of human diseases, including cancer, metabolic conditions and inflammatory bowel disease. Current approaches for detecting microbiome associations are limited by relying on specific measures of ecological distance, or only allowing for the detection of associations with individual bacterial species, rather than the whole microbiome. In this work, we develop a novel hierarchical Bayesian model for detecting global microbiome associations. Our method is not dependent on a choice of distance measure, and is able to incorporate phylogenetic information about microbial species. We perform extensive simulation studies and show that our method allows for consistent estimation of global microbiome effects. Additionally, we investigate the performance of the model on two real-world microbiome studies: a study of microbiome-metabolome associations in inflammatory bowel disease, and a study of associations between diet and the gut microbiome in mice. We show that we can use the method to reliably detect associations in real-world datasets with varying numbers of samples and covariates.

PMID:34714989 | DOI:10.1515/sagmb-2021-0047