Tag: statistics

Cancer Commun (Lond). 2022 Nov 4. doi: 10.1002/cac2.12383. Online ahead of print.

ABSTRACT

BACKGROUND: Although programmed cell death 1 (PD-1) blockade plus chemotherapy can significantly prolong the progression-free survival (PFS) and overall survival (OS) in first-line settings in patients with driver-negative advanced non-small-cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy.

METHODS: Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD-1 ligand (PD-L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan-Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations.

RESULTS: Responders had significantly higher CD8/PD-L1 (P = 0.015) or CD68/PD-L1 co-expression levels (P = 0.021) than non-responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co-expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co-expression subgroups. The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression, the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD-L1 co-expression group.

CONCLUSION: Tumor immune microenvironmental marker expression, especially CD8/PD-L1 or CD68/PD-L1 co-expression, was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.

PMID:36331328 | DOI:10.1002/cac2.12383

Eur Heart J. 2022 Nov 4:ehac594. doi: 10.1093/eurheartj/ehac594. Online ahead of print.

ABSTRACT

BACKGROUND: Inclisiran, an siRNA administered twice-yearly, significantly reduced LDL cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a lower risk of cardiovascular (CV) events is not yet established.

METHODS AND RESULTS: Patient-level, pooled analysis of ORION-9, -10 and -11, included patients with heterozygous familial hypercholesterolaemia, atherosclerotic CV disease (ASCVD), or ASCVD risk equivalent on maximally tolerated statin-therapy, randomized 1:1 to receive 284 mg inclisiran or placebo on Days 1, 90, and 6-monthly thereafter for 18 months. Prespecified exploratory endpoint of major cardiovascular events (MACEs) included non-adjudicated CV death, cardiac arrest, non-fatal myocardial infarction (MI), and fatal and non-fatal stroke, evaluated as part of safety assessments using a standard Medical Dictionary for Regulatory Activities basket. Although not prespecified, total fatal and non-fatal MI, and stroke were also evaluated. Mean LDL-C at baseline was 2.88 mmol/L. At Day 90, the placebo-corrected percentage reduction in LDL-C with inclisiran was 50.6%, corresponding to an absolute reduction of 1.37 mmol/L (both P < 0.0001). Among 3655 patients over 18 months, 303 (8.3%) experienced MACE, including 74 (2.0%) fatal and non-fatal MIs, and 28 (0.8%) fatal and non-fatal strokes. Inclisiran significantly reduced composite MACE [OR (95% CI): 0.74 (0.58-0.94)], but not fatal and non-fatal MIs [OR (95% CI): 0.80 (0.50-1.27)] or fatal and non-fatal stroke [OR (95% CI): 0.86 (0.41-1.81)].

CONCLUSION: This analysis offers early insights into the potential CV benefits of lowering LDL-C with inclisiran and suggests potential benefits for MACE reduction. These findings await confirmation in the larger CV outcomes trials of longer duration.

PMID:36331326 | DOI:10.1093/eurheartj/ehac594

Eur Heart J. 2022 Nov 4:ehac615. doi: 10.1093/eurheartj/ehac615. Online ahead of print.

ABSTRACT

AIMS: Patients often require combination therapies to achieve LDL cholesterol (LDL-C) targets for the primary prevention of atherosclerotic cardiovascular disease. This study investigates the effect of inclisiran, a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 production, in primary prevention patients with elevated LDL-C despite statins.

METHODS AND RESULTS: This pre-specified analysis of the placebo-controlled, randomized ORION-11 trial included 203 individuals at risk of, but without prior, cardiovascular events and LDL-C ≥2.6 mmol/L, despite maximally tolerated statins. Inclisiran 284 mg or placebo was administered on Days 1, 90, and thereafter every 6 months up to 540 days. Co-primary endpoints were percentage LDL-C change from baseline to Day 510 and time-adjusted change from baseline after Day 90 and up to Day 540. Key secondary endpoints included percentage and absolute changes in atherogenic lipoproteins. Safety was assessed over 540 days. The mean baseline (SD) LDL-C was 3.6 (1.5) mmol/L. At Day 510, the placebo-corrected LDL-C change with inclisiran was -43.7% [95% confidence interval (CI): -52.8 to -34.6] with a corresponding time-adjusted change of -41.0% (95% CI: -47.8 to -34.2); (P < 0.0001). The placebo-corrected absolute change in LDL-C at Day 510 with inclisiran was -1.5 mmol/L (95% CI: -1.8 to -1.2), with a respective time-adjusted change of -1.3 mmol/L (95% CI: -1.6 to -1.1). Inclisiran significantly lowered non-HDL cholesterol and apolipoprotein B (apoB) at Day 510 vs. placebo (P < 0.0001 for both), with a greater likelihood of attaining lipoprotein and apoB goals, and was well-tolerated except for mainly mild, treatment-emergent adverse events at the injection site.

CONCLUSION: Inclisiran was generally well-tolerated in primary prevention patients with elevated LDL-C, who derived significant reductions in atherogenic lipoprotein levels with twice-yearly maintenance dosing.

PMID:36331315 | DOI:10.1093/eurheartj/ehac615

Dentomaxillofac Radiol. 2022 Nov 4:20220223. doi: 10.1259/dmfr.20220223. Online ahead of print.

ABSTRACT

OBJECTIVE: To establish prevalence and severity of external cervical resorption (ECR) in posterior teeth observed in bitewing (BW) radiographs in an epidemiological study of a 17-year-old patient population from community dentistry. Furthermore, to assess potential predisposing factors for ECR.

METHODS: Posterior BWs from 5,596 patients (2,717 females, 2,879 males; mean age 17.8 years) were assessed by three observers in order to detect ECR (using Heithersay’s classification system, severity classes 1-4). When ECR was suspected, cone beam CT (CBCT) was offered to verify diagnosis. Prevalence was estimated based on ECR suspected in BWs and finally in CBCT. Possible predisposing factors (orthodontic treatment, trauma, and periodontal disease) were recorded and assessed for association with ECR.

RESULTS: In 41 patients, ECR was suspected in BWs (suspected prevalence 0.73%). Thirty-two patients accepted CBCT examination, of which eight were verified to have ECR (final prevalence 0.18%). In 24 patients, other disease entities and abnormal tooth morphology, that had mimicked ECR in BWs, excluded ECR in CBCT. ECR severity ranged from class 1-3 in BW and 2-4 in CBCT. All but one case had not been diagnosed by the patient’s community dentist. No statistically significant association between predisposing factors and ECR was identified.

CONCLUSIONS: ECR had low prevalence in this adolescent population, as observed in both BWs and CBCT. Still, early detection of ECR is important for treatment prognosis, and attention should be paid to this disease entity when assessing BWs obtained for other diagnostic purposes. CBCT may subsequently aid in verifying the disease.

PMID:36331310 | DOI:10.1259/dmfr.20220223

Ann Med. 2022 Dec;54(1):3146-3156. doi: 10.1080/07853890.2022.2139410.

ABSTRACT

BACKGROUND: Role models are essential in medical education, yet empirical research is relatively insufficient on the influence of prosocial modelling on medical students’ career commitment. The prosocial behaviour of medical staff involved in the fight against the novel coronavirus disease 2019 (COVID-19) at the beginning of 2020 presents an opportunity to fill the research gap. We explored and compared the different associations of the two most important role models for medical students – parents and faculty- with medical students’ career commitment.

METHODS: The cross-sectional study was conducted with 99,559 undergraduate students majoring in clinical medicine in mainland China. Questions were asked to collect information about participants in the battle against COVID-19, medical students’ determination to practice medicine after graduation, as well as students’ socio-demographic characteristics. Chi-square tests and hierarchical regressions were performed to examine the associations between parent and faculty involvement and students’ career commitment.

RESULTS: The results showed statistically significant associations between prosocial modelling during the COVID-19 pandemic in China and students’ intention to pursue medical careers. The association of faculty involvement (OR = 1.165, p < .001) with students’ career commitment was greater than that of parents (OR = 0.970, p > .05). For faculty involvement, the association was stronger among male students (OR = 1.323, p < .001) and students who were already determined to be doctors (OR = 1.219, p < .001) before the pandemic.

CONCLUSIONS: Our study provides new evidence on the potential roles of parents and faculty in shaping medical students’ career commitment. Encouraging faculty to act as positive role models could help medical students increase their intention to become doctors.KEY MESSAGESProsocial modelling could enhance students’ intention to pursue medical careers.The association of prosocial behaviour of faculty is larger than that of parents on medical students.Those who have prior medical career commitment are much more likely to persist in the medical profession, and prosocial modelling of faculty is positively associated with their medical career commitment.

PMID:36331292 | DOI:10.1080/07853890.2022.2139410

Transl Vis Sci Technol. 2022 Nov 1;11(11):3. doi: 10.1167/tvst.11.11.3.

ABSTRACT

PURPOSE: The purpose of the study was to determine if aqueous glucose levels rise in a comparable time frame to interstitial fluid and could therefore be suitable for a continuous glucose monitoring (CGM) site.

METHODS: An intravenous glucose tolerance test was performed on five New Zealand white rabbits. Aqueous humor from the posterior and anterior chamber of the eye and venous blood were sampled for glucose concentration measurement. Glucose concentrations in the interstitial fluids were monitored using a CGM system. A compartment model was created to map the glucose response curves in each compartment. The delay in rising glucose concentrations between blood and interstitial fluid and aqueous humor in the posterior chamber and anterior chamber of the eye were analyzed.

RESULTS: The results showed a statistically similar time lag and rate of change in glucose concentrations between blood and interstitial fluids or aqueous humor in either the posterior or anterior chamber.

CONCLUSIONS: The results of this study add further support to the aqueous humor being used as an alternative CGM site.

TRANSLATIONAL RELEVANCE: The study provides the basis for developing an intraocular continuous glucose sensor that can overcome limitations of current CGM systems.

PMID:36331274 | DOI:10.1167/tvst.11.11.3

Int Health. 2022 Nov 4:ihac067. doi: 10.1093/inthealth/ihac067. Online ahead of print.

ABSTRACT

BACKGROUND: Utilization of adequate and quality prenatal healthcare services confers critical benefits to women and their unborn children. However, utilization rates remain low in many countries in Africa. Several studies have attempted to understand the primary drivers behind these low statistics. This article contributes to this discourse by examining the associations between birth interval and timing and number/frequency of antenatal care visits in Africa.

METHODS: We pooled data from the publicly available Demographic and Health Surveys conducted in the last decade (2010-2020) for 32 African countries. Data were analysed using descriptive proportions and mixed effect binary logistic regression.

RESULTS: The results illustrate moderate significant associations between spacing on the most recent birth by ≥36 months and early (first trimester) first antenatal care contact in both our bivariate (odds ratio [OR] 1.18, p<0.001) and multivariate (OR 1.106, p<0.001) analyses. The benefits on optimal antenatal contacts predicted on spacing are also noticed with birth intervals of 24-35 months (OR 1.08, p<0.001) and ≥36 months (OR 1.48, p<0.001).

CONCLUSIONS: Optimal birth spacing is beneficial for ANC utilization in terms of timing and total number of contacts. Post-partum family planning/contraceptive use can be an effective pathway to prolonging birth intervals. We argue that maternal and child health programmes strengthen prioritizing contraceptive use between births.

PMID:36331288 | DOI:10.1093/inthealth/ihac067

Biostatistics. 2022 Nov 4:kxac043. doi: 10.1093/biostatistics/kxac043. Online ahead of print.

ABSTRACT

Most of the literature on joint modeling of longitudinal and competing-risk data is based on cause-specific hazards, although modeling of the cumulative incidence function (CIF) is an easier and more direct approach to evaluate the prognosis of an event. We propose a flexible class of shared parameter models to jointly model a normally distributed marker over time and multiple causes of failure using CIFs for the survival submodels, with CIFs depending on the “true” marker value over time (i.e., removing the measurement error). The generalized odds rate transformation is applied, thus a proportional subdistribution hazards model is a special case. The requirement that the all-cause CIF should be bounded by 1 is formally considered. The proposed models are extended to account for potential failure cause misclassification, where the true failure causes are available in a small random sample of individuals. We also provide a multistate representation of the whole population by defining mutually exclusive states based on the marker values and the competing risks. Based solely on the assumed joint model, we derive fully Bayesian posterior samples for state occupation and transition probabilities. The proposed approach is evaluated in a simulation study and, as an illustration, it is fitted to real data from people with HIV.

PMID:36331265 | DOI:10.1093/biostatistics/kxac043

Invest Ophthalmol Vis Sci. 2022 Nov 1;63(12):8. doi: 10.1167/iovs.63.12.8.

ABSTRACT

PURPOSE: To study the circumpapillary retinal nerve fiber layer (RNFL) birefringence (BIR) of early glaucoma and age-matched healthy eyes using polarization-sensitive optical coherence tomography (PS-OCT).

METHODS: In this prospective cross-sectional study, we compared virtual circular PS-OCT B-scans with a diameter of 3.5 mm centered on the optic disc (OD) acquired with a PS-OCT prototype (860 nm center wavelength). Early glaucoma was defined by the glaucomatous appearance of the OD and a pathologic visual field test with a mean deviation (MD) better than -6 dB. The main outcome parameters were BIR, RNFL-thickness (RNFL-T), and phase retardation (RET). The BIR value at each virtual A-scan position was the quotient of the RET measured at the inner segment/outer segment junction divided by the RNFL-T.

RESULTS: The dataset comprised 49 early glaucoma patients (mean ± standard deviation [SD]: 64 ± 10 years) and 49 healthy control subjects (61 ± 9 years). Glaucomatous eyes showed a statistically significant lower BIR globally (mean ± SD: 0.108 ± 0.008°/µm vs. 0.112 ± 0.009°/µm, P = 0.033), superiorly (0.116 ± 0.017°/µm vs. 0.126 ± 0.013°/µm, P = 0.0001), and inferiorly (0.112 ± 0.011°/µm vs. 0.121 ± 0.011°/µm, P < 0.0001), and increased BIR in the temporal quadrant (0.088 ± 0.015°/µm vs. 0.078 ± 0.014°/µm, P = 0.0001) compared to healthy eyes.

CONCLUSIONS: We report a reduced BIR of the RNFL in early perimetric glaucoma, which can be interpreted as a sign of loss or change of intracellular microtubules and may contribute to a better understanding of early disease development. Prospective longitudinal studies are needed to determine whether BIR is altered in pre-perimetric human glaucoma before RNFL-T decline.

PMID:36331260 | DOI:10.1167/iovs.63.12.8

Pediatr Int. 2022 Jan;64(1):e15341. doi: 10.1111/ped.15341.

ABSTRACT

BACKGROUND: Precordial Doppler ultrasound technology can be used to confirm correct peripheral intravenous access in children. Changes in precordial Doppler sound from the baseline after injecting normal saline are detected using a correct peripheral intravenous access. However, the location of the precordial Doppler probe has been inconsistent in previous studies. Our study aimed to determine whether the right or left parasternal border is the optimal location for precordial Doppler probe placement.

METHODS: This single-center, prospective interventional study was conducted between July 2021 and January 2022 and included children aged 1-6 years. The Doppler probe was placed under general anesthesia at the most audible site on the right and left parasternal borders of patients. Baseline heartbeat was recorded by the Doppler for 10 s on the right and left parasternal borders. After randomizing the order of the recorded data, two blinded raters separately listened to the data and decided the audibility of the sounds.

RESULTS: A total of 77 patients were enrolled in the study. The proportion of the audible baseline heartbeat was significantly higher on the left parasternal borders than on the right by both rater 1 (96.1%, 22.1%, p < 0.001) and rater 2 (96.1%, 27.3%, p < 0.001). Regarding inter-rater reproducibility, Cohen’s kappa statistics for the left and right parasternal borders were significant (0.65 and 0.79, both p < 0.001).

CONCLUSIONS: The baseline heartbeat was more audible on the left parasternal border than on the right parasternal border with acceptably high interrater reproducibility. This is inconsistent with the interpretations of previous reports.

PMID:36331222 | DOI:10.1111/ped.15341