Tag: statistics

Eur J Surg Oncol. 2021 Jul 20:S0748-7983(21)00635-1. doi: 10.1016/j.ejso.2021.07.014. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate the prognostic value of dual-energy CT (DECT) based radiomics to predict disease-free survival (DFS) and overall survival (OS) for patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC).

METHODS: From January 2014 to December 2018, a total of 156 AGC patients were enrolled and randomly allocated into a training cohort and a testing cohort at a ratio of 2:1. Volume of interest of primary tumor was delineated on eight image series. Four feature sets derived from pre-NAC and delta radiomics were generated for each survival arm. Random survival forest was used for generating the optimal radiomics signature (RS). Statistical metrics for model evaluation included Harrell’s concordance index (C-index) and the average cumulative/dynamic AUC throughout follow-up. A clinical model and a combined Rad-clinical model were built for comparison.

RESULTS: The pre-IU (derived from iodine uptake images before NAC) RS performed best for DFS and OS in the testing cohort (C-indices, 0.784 and 0.698; the average cumulative/dynamic AUCs, 0.80 and 0.77). When compared with the clinical model, the radiomics model had significantly higher C-index to predict DFS in the testing cohort (0.784 vs. 0.635, p < 0.001), but no statistical difference was found for OS (0.698 vs. 0.680, p = 0.473). The combined Rad-clinical models showed improved performance in the testing cohort, with C-indices of 0.810 and 0.710 for DFS and OS, respectively.

CONCLUSION: DECT-derived radiomics serves as a promising non-invasive biomarker to predict survival for AGC patients after NAC, providing an opportunity for transforming proper treatment.

PMID:34304951 | DOI:10.1016/j.ejso.2021.07.014

Auris Nasus Larynx. 2021 Jul 23:S0385-8146(21)00194-2. doi: 10.1016/j.anl.2021.07.002. Online ahead of print.

ABSTRACT

OBJECTIVE: Limited low frequency (LF) pitch and temporal fine structure (TFS) sensitivity have been thought to contribute significantly to poor music perception in cochlear implant (CI) listeners. Thus, this study aimed to evaluate music perception in relation to LF pitch perception and temporal coding, specifically in people with bimodal stimulation as a promising approach to improve spectro-temporal sensitivity in CI listeners.

METHODS: Eleven postlingually deafened bimodal listeners participated in the study (mean age=55.5 years, range 36-75 years, SD=11.7). LF pitch/TFS sensitivity was evaluated by using two recently developed tests: Harmonic Intonation (HI) and Disharmonic Intonation (DI). The music perception protocol was based on three audio files in the genres of Classical, Jazz and Soul music and a music quality questionnaire regarding four subjective aspects: Clarity, Pleasantness, Naturalness and General Quality of Sounds.

RESULTS: CI alone and bimodal findings showed statistically significant differences for both temporal coding and music perception. DI findings showed statistically significant correlations with music quality ratings (p<0.05).

CONCLUSION: Bimodal music quality ratings were significantly better, indicating a significant improvement in the quality of music towards being significantly more clear, more natural, more pleasant, and better quality. Similarly, bimodal HI/DI findings improved significantly, although the amount of benefit was greater for the DI task with spectral information only below 300 Hz. Significant DI correlations with music quality ratings supported the test to be more indicative of better temporal coding of LF residual hearing and its effects on music perception.

PMID:34304943 | DOI:10.1016/j.anl.2021.07.002

Ann Emerg Med. 2021 Jul 23:S0196-0644(21)00300-0. doi: 10.1016/j.annemergmed.2021.04.017. Online ahead of print.

ABSTRACT

STUDY OBJECTIVE: Patient experience metrics have become increasingly important in evaluations of health care organizations and physician performance. Although such measures have been touted as a way to make objective comparisons of performance, they are subject to many of the same biases as other survey instruments, including gender bias.

METHODS: A total of 320 surveys were conducted between February and October 2020. Surveys included vignettes describing different scenarios, and respondents were asked to rate the vignette physician in each scenario on 1 of 3 themes: listening, time, or courtesy. Three vignettes per theme were used. Half of the surveys used a male physician and half used a female physician. Using tests of difference, we compared the ratings of male and female vignette physicians. We also used a statistical technique known as anchoring vignettes to show how respondents’ ratings of vignette physicians related to their ratings of their own physicians.

RESULTS: In all 9 vignette scenarios, the male vignette physician was rated more highly than the female vignette physician. These differences were statistically significant in 2 of 9 scenarios. Male vignette physicians were given more top-box ratings than female vignette physicians. Anchoring vignettes showed a statistically nonsignificant association between vignette ratings and ratings of respondents’ own physicians.

CONCLUSION: Our findings revealed a pattern of higher ratings of male vignette physicians when compared to female vignette physicians, which may translate to ratings of patients’ own physicians. These findings suggest that current methods to evaluate patients’ experiences with their own physicians may disadvantage female physicians.

PMID:34304916 | DOI:10.1016/j.annemergmed.2021.04.017

Burns. 2021 Jul 7:S0305-4179(21)00162-5. doi: 10.1016/j.burns.2021.06.007. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe incidence and characteristics of hospital presentations and deaths due to burn injury in the Australian state of Victoria from 2008 to 2017 and identify trends in incidence and patterns.

METHODS: Three population-based datasets were used to ascertain burn-related hospital admissions, emergency department presentations, and deaths. These were the Victorian Admitted Episodes Dataset (VAED), Victorian Emergency Minimum Dataset (VEMD), and the Cause of Death-Unit Record File (COD-URF), respectively. Descriptive statistics on demographics (age and gender), burn injury characteristics (intent, cause, burn size and body region) and hospital burden (length of stay (LOS) and costs) were used to present the profile of patients. Incidence rates by age, gender and intent were calculated. Trend analysis on incidence was carried out using forced Poisson Regression models with the natural logarithm of the annual populations as an offset. Incident rate ratios were used to interpret the models. Risk ratios were used to compare the risk differences between population sub-groups. A negative binomial model was used to test the association between LOS and age and the total body surface area (TBSA) of the burn.

RESULTS: Overall males had higher rates of death, admission and ED presentation. For adults, the elderly had the highest rates of deaths and admissions while for children, the very young had highest rates for admissions and presentations. Exposure to smoke, fire and flames was the most common cause of deaths, and contact with heat and hot substances was most common among ED presentations. The elderly and those with Total Body Surface Area (TBSA) burn ≥20% had a higher risk of longer hospital stay. Rates of severe burns and deaths from burns remained stable during the study period in the setting of an annual 2% increase in population. Paediatric hospital admission rates decreased over time.

CONCLUSION: The risk of sustaining burn injury, the types of burn and outcomes, varied by age and gender. We found evidence of a limited decrease in burn injury rates in some sub-groups: appropriate and effective targeted prevention strategies for burns are needed to avoid the significant short and long-term suffering experienced.

PMID:34304930 | DOI:10.1016/j.burns.2021.06.007

Clin Ther. 2021 Jul 22:S0149-2918(21)00231-9. doi: 10.1016/j.clinthera.2021.06.001. Online ahead of print.

ABSTRACT

PURPOSE: Evogliptin is one of the latest dipeptidyl peptidase-4 (DPP-4) inhibitor, and a number of clinical trials have been performed following its development, including several randomized controlled trials (RCTs) performed to evaluate its efficacy and tolerability. In our study, we performed a systematic review and meta-analysis of its efficacy and tolerability by collecting RCTs and confirmed the results with Bayesian inference. Moreover, an updated quality-management system was integrated into the study process of systematic review.

METHODS: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for literature published between May 1990 and November 2020. We selected 6 homogeneous RCTs in 1017 subjects for efficacy and 1070 subjects for tolerability analysis. Regarding the efficacy profile, the mean differences from baseline (95% CIs) in hemoglobin (Hb) A_1c and fasting plasma glucose (FPG) were generated as end points and derived from each study. Regarding the tolerability profile, risk ratios of adverse events (AEs), serious AEs, adverse drug reactions, and hypoglycemia were generated from baseline to outcome measurements as derived from each study. A subsequent meta-analysis was performed with Bayesian inference.

FINDINGS: For HbA_1c and FPG, the results suggested a statistically significant improvement with evogliptin versus placebo (HbA_1c, -0.44 [95% CI, -0.54 to -0.34; P < 0.00001] and posterior median, -0.38 [95% CI, -0.51 to -0.24]; FPG, -0.61 [95% CI, -0.90 to -0.31; P < 0.0001] and posterior median, -0.48 [95% CI, -0.90 to -0.16]), but no statistically significant difference with evogliptin versus other DPP-4 inhibitors (HbA_1c, -0.01 [95% CI, -0.14 to 0.12] and posterior median, -0.06 [95% CI, -0.25 to 0.12]; FPG, 0.17 [95% CI, -0.10 to 0.44] and posterior median, 0.27 [95% CI, -0.12 to 0.65]). In terms of tolerability, the overall prevalence of adverse events, including hypoglycemia, was similar between evogliptin and other DPP-4 inhibitors and placebo.

IMPLICATIONS: Evogliptin appears more efficacious in terms of changes in HbA_1c and FPG compared with placebo, with an efficacy comparable to those of other DPP-4 inhibitors, although with the limited data studied and the minuscule sample sizes, the predictions of posterior medians, mean differences, and risk ratios of HbA_1c, FPG, and AEs by Bayesian inference were consistent with our findings through our quality-management system.

PMID:34304912 | DOI:10.1016/j.clinthera.2021.06.001

Clin Ther. 2021 Jul 22:S0149-2918(21)00219-8. doi: 10.1016/j.clinthera.2021.05.004. Online ahead of print.

ABSTRACT

PURPOSE: This study evaluated antipyretic efficacy and onset of a novel fixed-dose combination (FDC) of ibuprofen (IBU; 250 mg) and acetaminophen (APAP; 500 mg) compared with placebo and IBU or APAP monocomponents. MET: This single-center, randomized, double-blind, placebo-controlled, full-factorial study was conducted in healthy males aged 18 to 55 years with pyrexia induced by intravenous administration of reference standard endotoxin (RSE). After attainment of an oral temperature ≥38.1°C, subjects were randomized 3:3:3:1 to a double-blind single oral dose of FDC IBU/APAP 250 mg/500 mg, APAP 500 mg, IBU 250 mg, or placebo. Oral temperature was measured every 10 minutes for 2 hours, then every 30 minutes until 8 hours postdose. Time-weighted sum of temperature differences from baseline to 8 hours (WSTD_0-8) after study medication administration was the primary efficacy end point. Secondary end points included WSTD scores from 0 to 2 hours, 0 to 4 hours, 0 to 6 hours, and 6 to 8 hours; time to return to “normal” temperature; time to rescue medication use; and global drug evaluation. Safety was assessed via adverse events (AEs).

FINDINGS: Two hundred ninety subjects were randomized; 273 were included in the primary efficacy analysis. WSTD_0-8 was significantly better for FDC IBU/APAP 250 mg/500 mg (P = 0.002), IBU 250 mg (P = 0.030), and APAP 500 mg (P = 0.023) versus placebo; there were no significant differences between active treatments. For WSTD_0-2, only the FDC was statistically significant versus placebo (P = 0.004). All active treatments were significantly better (P < 0.05) for WSTD_0-4 and WSTD_0-6 versus placebo; there were no differences in WSTD_6-8 between cohorts. Temperature returned to normal during the 8-hour treatment period in ∼50% of subjects in each cohort. Only 1 subject (IBU cohort) took rescue medication. Post hoc analyses at early time points revealed significant treatment differences favoring FDC versus placebo and IBU for the WSTD from baseline during the 50- to 110-minute posttreatment window; for WSTD from baseline during the 80- to 110-minute posttreatment window, FDC provided significant treatment differences versus placebo and both monocomponents. Overall, 223 (76.9%) of 290 subjects experienced AEs related to RSE; only 2 subjects experienced treatment-related AEs (FDC, rash; placebo, ear pain).

IMPLICATIONS: Although the primary end point was not met, these results suggest that FDC IBU/APAP 250 mg/500 mg provides effective antipyresis with a faster onset versus equal doses of IBU and APAP alone. ClinicalTrials.gov identifier: NCT02761980. (Clin Ther. 2021;43:XXX-XXX) © 2021 Elsevier HS Journals, Inc.

PMID:34304913 | DOI:10.1016/j.clinthera.2021.05.004

J Pediatr Surg. 2021 Jul 7:S0022-3468(21)00482-6. doi: 10.1016/j.jpedsurg.2021.06.011. Online ahead of print.

ABSTRACT

BACKGROUND: Wide practice variation exists in the management of gastroschisis. Routine endotracheal intubation for bedside closure may lead to longer duration of mechanical ventilation.

METHODS: The Canadian Association of Pediatric Surgery Network gastroschisis dataset was queried for all patients undergoing attempted bedside reduction and closure. Patients with evidence of intestinal necrosis or perforation were excluded. A propensity score analysis was used to compare the rate of successful primary repair and post-operative outcomes between intubated and non-intubated patients.

RESULTS: In propensity score matched analysis, the successful primary repair rate did not reach statistical significance between patients who were intubated for attempted bedside closure and those who were not intubated (Odds Ratio: 2.18, 95% Confidence Interval: 0.79, 6.03). Intubated patients experienced 3.02 more ventilator days than patients who were not intubated at the time of initial attempted closure. Other post-operative parameters were similar between both groups.

CONCLUSIONS: It is reasonable to attempt primary bedside gastroschisis closure without intubation in otherwise healthy infants.

PMID:34304903 | DOI:10.1016/j.jpedsurg.2021.06.011

Gynecol Oncol. 2021 Jul 22:S0090-8258(21)00590-4. doi: 10.1016/j.ygyno.2021.07.028. Online ahead of print.

ABSTRACT

OBJECTIVE: A recent study showed that even a few months of breastfeeding is associated with a significant decrease in the risk of ovarian cancer in the general population. This study aimed to perform a systematic review and meta-analysis to determine the significance of the length of the breastfeeding period on ovarian cancer risk in BRCA1/2 mutation carriers.

METHODS: PubMed, EMBASE, and Cochrane databases were searched up to June 1, 2021. We included case-control and cohort studies that contained information on breastfeeding and the risk of ovarian cancer in BRCA1/2 mutation carriers. Odds ratios (OR) were meta-analytically pooled using a fixed-effects model.dd RESULTS: Five studies, including one cohort study and four case-control studies, were included in this meta-analysis. Of the 14,601 BRCA1/2 mutation carriers, the overall pooled OR of ever having performed breastfeeding in patients who had ovarian cancer was 0.767 (95% confidence interval [CI], 0.688-0.856) and 0.817 (95% CI, 0.650-1.028) for patients with BRCA1 and BRCA2 mutation, respectively. Breastfeeding for >1 year acted as a protective factor in both BRCA1 [OR: 0.787 (95% CI, 0.682-0.907)] and BRCA2 [OR: 0.567 (95% CI, 0.400-0.802)] mutation carriers. No significant heterogeneity was present (I2 = 0%), and the funnel plot was also properly distributed, showing no publication bias.

CONCLUSIONS: Breastfeeding is a preventive, modifiable factor for ovarian cancer in BRCA1/2 mutation carriers. Ever having performed breastfeeding was significantly preventive for ovarian cancer in the BRCA1 mutation carriers, however a period of 1 year or more of breastfeeding is required for a reduced ovarian cancer risk in BRCA2 mutation carriers.

PMID:34304906 | DOI:10.1016/j.ygyno.2021.07.028

Gynecol Oncol. 2021 Jul 22:S0090-8258(21)00585-0. doi: 10.1016/j.ygyno.2021.07.023. Online ahead of print.

ABSTRACT

This study aimed to prospectively evaluate the impact of dose-escalated irradiation of nodal metastases on clinical outcomes compared to no boost in patients with node-positive, bulky, locally advanced cervical cancer (LACC) undergoing standard chemoradiation and MRI-based brachytherapy.

METHODS: This comparative study included 161 patients with node-positive LACC treated with definitive chemoradiation and MRI-based brachytherapy. The prospective Boost arm accrued 71 patients to receive nodal boost either sequentially or simultaneously to an equivalent dose of 60 Gy. The control arm comprised 90 patients treated before this protocol period with no additional nodal boost.

RESULT: Baseline patient and tumor characteristics were similar in both groups. All patients had at least one tumor dimension >5 cm at presentation, and 31% had para-aortic node involvement. With a median follow-up of 36 months (IQR:19-50.5), the overall 3-year Local control rate was 88.8%. The 3-year Regional control (93% vs. 80%, p = 0.035) was statistically better in the Boost arm. No nodal failure was observed in nodes <3 cc and < 2 cm, even in the No-boost arm. There was no significant difference in Disease-free survival (67.6% vs. 58.9%,p = 0.454) and Overall Survival (78.9% vs. 74.4%,p = 0.87) between the two arms. Incidence of acute or late toxicities did not differ significantly with nodal boost or the boost delivery technique.

CONCLUSION: The addition of external radiation nodal boost to standard treatment of high-volume cervical cancer has improved pelvic control with an acceptable rate of toxicities. However, high systemic failures continue to pose a challenge in improving survival outcomes.

PMID:34304907 | DOI:10.1016/j.ygyno.2021.07.023

Biol Psychiatry. 2021 May 4:S0006-3223(21)01263-4. doi: 10.1016/j.biopsych.2021.04.018. Online ahead of print.

ABSTRACT

BACKGROUND: Polygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies. PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in applications to real data sets, which could reflect a number of factors, e.g., phenotype definition or technical factors.

METHODS: The Psychiatric Genomics Consortium Working Groups for schizophrenia and major depressive disorder bring together many independently collected case-control cohorts. We used these resources (31,328 schizophrenia cases, 41,191 controls; 248,750 major depressive disorder cases, 563,184 controls) in repeated application of leave-one-cohort-out meta-analyses, each used to calculate and evaluate PGS in the left-out (target) cohort. Ten PGS methods (the baseline PC+T method and 9 methods that model genetic architecture more formally: SBLUP, LDpred2-Inf, LDpred-funct, LDpred2, Lassosum, PRS-CS, PRS-CS-auto, SBayesR, MegaPRS) were compared.

RESULTS: Compared with PC+T, the other 9 methods gave higher prediction statistics, MegaPRS, LDPred2, and SBayesR significantly so, explaining up to 9.2% variance in liability for schizophrenia across 30 target cohorts, an increase of 44%. For major depressive disorder across 26 target cohorts, these statistics were 3.5% and 59%, respectively.

CONCLUSIONS: Although the methods that more formally model genetic architecture have similar performance, MegaPRS, LDpred2, and SBayesR rank highest in most comparisons and are recommended in applications to psychiatric disorders.

PMID:34304866 | DOI:10.1016/j.biopsych.2021.04.018