Category: Statistics

Pediatr Blood Cancer. 2022 Jun 2:e29801. doi: 10.1002/pbc.29801. Online ahead of print.

ABSTRACT

BACKGROUND: Brentuximab vedotin (BV) is an antibody drug-conjugated anti-CD30 approved for the treatment of adult classical Hodgkin’s lymphoma (HL), whereas it is considered as off-label indication in paediatrics. The aim of the study was to evaluate the safety and efficacy of BV to treat patients aged less than 18 years with refractory/relapsed HL.

MATERIALS AND METHODS: In this multicentre, retrospective study, 68 paediatric patients who received at least one dose of BV between November 2011 and August 2020 were enrolled. A median of nine doses of BV were administered as monotherapy (n = 31) or combined with other therapies (n = 37). BV was administrated alone as consolidation therapy after stem cell transplantation (SCT) in 12 patients, before SCT in 18 patients, whereas in 15 patients it was used before and after SCT as consolidation therapy. Median follow-up was 2.8 years (range: 0.6-8.9 years).

RESULTS: The best response was observed in the 86% of patients; the overall response rate was 66%. The 3-year progression-free survival was 58%, whereas the overall survival was 75%. No statistically significant differences between patients treated with BV monotherapy or combination were highlighted. In multivariate analysis, patients with non-nodular sclerosis HL and not transplanted had an increased risk of failure. Overall, 46% of patients had grade 3-4 adverse events that led to BV discontinuation in five of them.

CONCLUSION: In conclusion, our study confirms that BV was a safe and effective drug, able to induce complete remission, either as monotherapy or in association with standard therapy.

PMID:35656841 | DOI:10.1002/pbc.29801

Stroke. 2022 Jun 3:101161STROKEAHA122038662. doi: 10.1161/STROKEAHA.122.038662. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertension is a risk factor of poor stroke outcomes and associated with antiplatelet resistance. This study aimed to explore the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in patients with different hypertension status, using randomized trial data from the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II).

METHODS: A total of 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles were enrolled and randomized to either ticagrelor-aspirin or clopidogrel-aspirin group. Hypertension status were classified into no, newly diagnosed, and previously diagnosed hypertension according to medical history, blood pressure, and antihypertensive medications during hospitalization. The primary efficacy and safety outcomes were stroke recurrence and moderate to severe bleeding risk within 90-day follow-up.

RESULTS: Ticagrelor-aspirin was associated with reduced risk of new stroke in patients without hypertension (32 [4.8%] versus 60 [7.2%]; hazard ratio, 0.55 [95% CI, 0.35-0.86]), but not in those with a newly diagnosed hypertension (20 [5.3%] versus 36 [9.1%]; hazard ratio 0.59 [95% CI, 0.33-1.07]), or those with a previously diagnosed hypertension (139 [7.0%] versus 147 [7.4%]; hazard ratio, 0.93 [95% CI, 0.74-1.18]) compared with clopidogrel-aspirin (P=0.04 for interaction). The risk of bleeding for ticagrelor-aspirin was not associated with hypertension status (0.1% versus 0.4%; 0.3% versus 0.5%, 0.4% versus 0.3%, P=0.50 for interaction). All the efficacy and safety outcomes between treatments did not differ by blood pressure levels on admission.

CONCLUSIONS: In the CHANCE-2 trial, patients without hypertension received a significantly greater benefit from ticagrelor- aspirin than those with previous hypertension after minor stroke or transient ischemic attack, and a similar benefit trend was observed in those with newly diagnosed hypertension.

REGISTRATION: URL: http://www.

CLINICALTRIALS: gov; Unique identifier: NCT04078737.

PMID:35656824 | DOI:10.1161/STROKEAHA.122.038662

Ann Otol Rhinol Laryngol. 2022 Jun 3:34894221098802. doi: 10.1177/00034894221098802. Online ahead of print.

ABSTRACT

OBJECTIVES: Hypopharyngeal and laryngeal cancers are aggressive and usually diagnosed at advanced stage with esophagus invasion. Total pharyngolaryngoesophagectomy with gastric pull-up reconstruction has been a common surgery for these cancers but long-term outcomes are still questionable. This study aimed to investigate short-term and long-term outcomes of patients who underwent this surgery.

METHODS: Patients with hypopharyngeal or laryngeal cancer invading cervical esophagus who underwent total pharyngolaryngoesphagectomy with gastric pull-up between 2012 and 2016 was included and followed up until 2021. Short-term outcomes were complications and long-term outcomes were overall survival (OS) and disease-free survival (DFS).

RESULTS: Fifty patients were included with a mean age of 60.3 years and 94% were male. Pyriform fossa was the most common primary site of tumor (50%), followed by posterior hypopharyngeal wall (18%) and postcricoid region (18%). Mean operating time, postoperative oral intake and hospital stay was 363.1 ± 43.6 minutes, 8.8 ± 3.6 days and 14.2 ± 3.0 days respectively. Complications occurred in 15 patients (30%) without any in-hospital death. During the follow-up period, 17 patients had recurrence and 35 patients died. Median (95% confidence interval [CI]) OS and DFS time were 30 (21-37) and 30 (19-36) months. Five-year OS and DFS probability (95% CI) were 22.6% (12.8-39.7) and 22.7% (12.9-39.8).

CONCLUSIONS: Total pharyngolaryngoesophagectomy with gastric pull-up is feasible and safe. However, even with curative surgery and multimodal treatment, advanced pharyngeal or laryngeal cancer with cervical esophagus invasion still has poor survival outcome.

PMID:35656819 | DOI:10.1177/00034894221098802

J Biopharm Stat. 2022 Jun 3:1-18. doi: 10.1080/10543406.2022.2058524. Online ahead of print.

ABSTRACT

This research focuses on the bias and type I error control issues when the marginal structural models (MSMs) are applied to evaluate the causal survival benefits of active intervention versus control in randomized clinical trials (RCTs) with treatment switching after disease progression. When MSMs are applied in the RCT setting, the question of interest, model specifications, strategies for type I error control, bias reduction, etc. differ somewhat from those for observational studies. This manuscript discusses the approaches used to accommodate these differences. Through Monte Carlo simulations and a case study, our research demonstrates that, with sufficient attention paid to issues applicable to RCTs in particular, MSMs may perform better than the inverse probability of censoring weighting (IPCW) method in analyzing the survival endpoint in RCTs with treatment switching because more information is used by the MSM.

PMID:35656809 | DOI:10.1080/10543406.2022.2058524

Ann Otol Rhinol Laryngol. 2022 Jun 3:34894221100024. doi: 10.1177/00034894221100024. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare NIH funding in the field of Otolaryngology to other medical and surgical specialties between 2009 and 2019.

METHODS: Data was collected from the NIH RePORTER database on funding dollars received by each specialty from 2009 to 2019. Along with data on total active physicians per specialty using the Physician Specialty Data Book, comparisons were drawn between Otolaryngology and other medical and surgical specialties with regards to trends in total funding and NIH funding dollars per physician. The distributions of grant funding, within Otolaryngology from various NIH institutes among principal investigators, organizations, and subspecialties were further explored.

RESULTS: There were 3810 grants (1147 unique projects) for a total of $1 276 198 555 funded by the NIH to Otolaryngology departments from 2009 to 2019. Statistically insignificant funding increases (P > .05) caused otolaryngology to fall from first to fourth in funding among studied specialties. The National Institute on Deafness and Other Communication Disorders funded 57% of all unique projects, and 57.2% of all unique NIH projects were otology related. Most projects were basic science related. The top 10 principal investigators obtained 22.3% of the total NIH funding for Otolaryngology. The top 3 organizations over the studied period comprised 26.55% of the total funding, generating a combined 729 grants. Among principal investigators, 63.0% had a PhD degree, 25.3% had an MD, and 9.6% had an MD/PhD.

CONCLUSION AND RELEVANCE: NIH funding in Otolaryngology has remained stable and is highly concentrated among a small number of organizations, geographic regions, and principal investigators. Recent initiatives by academic communities have sought to address funding disparities by incorporating diversity and inclusion into clinician-scientist pipelines. We urge our colleagues to strive toward identification of the factors that contribute to successful acquisition of funding and implementation of a more conducive institutional infrastructure to produce research.

PMID:35656790 | DOI:10.1177/00034894221100024

Brain. 2022 Jun 3:awac193. doi: 10.1093/brain/awac193. Online ahead of print.

ABSTRACT

There is increasing evidence on inflammation as a determinant in the pathogenesis of Parkinson’s disease. But, its role in parkinsonian neurodegeneration remains elusive: it´s not clear if inflammatory cascades are causes or consequences of dopamine neurons death. In the present study, we aim at performing an in-depth statistical investigation of the causal relationship between inflammation and Parkinson’s disease using a two-sample Mendelian randomization design. Genetic instruments were selected using summary-level data from the largest to date genome-wide association studies (sample size ranging from 13,955 to 204,402 individuals) conducted on European population for the following inflammation biomarkers: C-reactive protein, interleukin-6, interleukin 1 receptor antagonist, and tumor necrosis factor α. Genetic association data on Parkinson’s disease (56,306 cases and 1,417,791 controls) and age at onset of Parkinson’s disease (28,568 cases) were obtained from the International Parkinson’s Disease Genomics Consortium. On primary analysis, causal associations were estimated on sets of strong (P-value < 5 × 10-8; F-statistic > 10) and independent (linkage disequilibrium r2<0.001) genetic instruments using the inverse-variance weighted method. In sensitivity analysis, we estimated causal effects using robust Mendelian randomization methods and after removing pleiotropic genetic variants. Reverse causation was also explored. We repeated the analysis on different data sources for inflammatory biomarkers to check findings’ consistency. In all the three data sources selected for interleukin-6, we found statistical evidence for earlier age at onset of Parkinson’s disease associated with increased interleukin-6 concentration (years difference per 1 log-unit increase = -2.364, 95% CI = -4.789 to 0.060; years difference per 1 log-unit increase = -2.011, 95% CI = -3.706 to -0.317; years difference per 1 log-unit increase = -1.569, 95% CI = -2.891 to -0.247; ). We did not observe any statistical evidence for causal effects of C-reactive protein, interleukin 1 receptor antagonist, and tumor necrosis factor α on both Parkinson’s disease and its age at onset. Results after excluding possible pleiotropic genetic variants were consistent with findings from primary analyses. When investigating reverse causation, we did not find evidence for a causal effect of Parkinson’s disease or age at onset on any biomarkers of inflammation. We found evidence for a causal association between the onset of Parkinson’s disease and interleukin-6. The findings of this study suggest that the pro-inflammatory activity of the interleukin-6 cytokine could be a determinant of prodromal Parkinson’s disease.

PMID:35656776 | DOI:10.1093/brain/awac193

Pediatrics. 2022 Jun 3:e2021055229. doi: 10.1542/peds.2021-055229. Online ahead of print.

ABSTRACT

CONTEXT: Equine-assisted therapy in different facets aims to improve the clinical condition of children with cerebral palsy. A more comprehensive overview on the overall effects and on the differences between different treatment modalities seems desirable.

OBJECTIVE: We compared the effectiveness of various equine-assisted treatments on motor capabilities and quality of life of children with cerebral palsy.

DATA SOURCES: We conducted systematic searches of PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials.

STUDY SELECTION: Randomized and nonrandomized controlled parallel-group or crossover studies on equine-assisted therapies in comparison with standard of care were included.

DATA EXTRACTION: Data on motor function assessed by different instruments were considered as the primary outcome. Secondary outcomes included global, social, physical, and emotional scores of quality of life.

RESULTS: Strong evidence for a positive effect of equine-assisted therapies, particularly hippotherapy, on global gross motor function and motor capabilities during walking in children with cerebral palsy was identified (SMD 0.24, 95% CI 0.05 to 0.43, P = .01, t2 = 0.00, I2 = 15%; SMD 2.68, 95% CI 1.02 to 4.34, P = .002, t2 = 0.0, I2 = 0%). No evidence for the improvement in quality of life could be shown in the global assessment, nor in any subscore.

CONCLUSIONS: Equine-assisted therapy, particularly hippotherapy, can be a therapeutic tool for children who are learning to walk.

LIMITATION: The heterogeneity of tools used in different studies and the low number of studies addressing quality of life issues limited the number of studies available for distinct analyses.

PMID:35656779 | DOI:10.1542/peds.2021-055229

Sci Prog. 2022 Apr-Jun;105(2):368504221103763. doi: 10.1177/00368504221103763.

ABSTRACT

The aim of this study was to explain the mechanical differences between EdgeTaper Platinum (ETP) and ProTaper Gold (PTG) determining the transition temperatures and the composition of the alloy of ETP, since no data are present in literature. A total of 130 instruments were selected: 65 ETP F2 and 65 PTG F2. 20 instruments per type were submitted to each mechanical tests. The cyclic fatigue and torsional tests were performed at a pre-set temperature of 35 °C ± 1 °C. During the cyclic fatigue test, Time to fracture, number of cycles to fracture (NCF) and the fragment length (FL) were recorded. During the static torsional, Torque to Fracture (TtF) and FL were recorded. The fracture surface of 5 randomly selected fragments from each test was examined through a Scanning Electron Microscopy (SEM) and an EDX analysis was performed. 20 instruments per type were submitted to a bending test The force generated (grams) to bend each was recorded. Recorded data of mechanical and metallurgical tests were statistically analyzed using a one-way analysis of variance (ANOVA) test with significance set to a 95% confidence level. ETP F2 showed a higher cyclic fatigue resistance and bending ability than PTG F2, with a statistically significant difference (p < 0.05). PTG showed a higher torsional resistance with a statistically significant difference (p < 0.05). DSC analysis of 5 samples for each instrument type pointed out that the austenite finish temperature of PTG was higher than the ETP, respectively of 49.99 ± 3.31 (°C) and 38.92 ± 1.75 (°C). EDX analysis confirmed the near-equiatomic composition of the Ni-Ti alloys, with a presence of a third component recognized as rubidium in the ETP samples. ETP showed higher flexibility in comparison with PTG, despite the latter is characterized by a more martensitic characterization. since its Af temperature is higher than the ETP.

PMID:35656775 | DOI:10.1177/00368504221103763

J Child Neurol. 2022 Jun 3:8830738221100327. doi: 10.1177/08830738221100327. Online ahead of print.

ABSTRACT

Objective: The primary aim of this study is to develop an easy way to identify migraine phenotype posttraumatic headache (MPTH) in children with traumatic brain injury, to treat headache in traumatic brain injury effectively, and to promote faster recovery from traumatic brain injury symptoms overall. Methods: We evaluated youth aged 7-20 years in a pediatric neurology traumatic brain injury (TBI) clinic, assigning a migraine phenotype for post-traumatic headache (MPTH) at the initial visit with the 3-item ID Migraine Screener. We stratified the sample by early (≤6 weeks) and late (>6 weeks) presenters, using days to recovery from concussion symptoms as the primary outcome variable. Results: 397 youth were assessed; 54% were female. Median age was 15.1 years (range 7.0-20.4 years), and 34% of the sample had sports-related injuries. Migraine phenotype for posttraumatic headache (MPTH) was assigned to 56.1% of those seen within 6 weeks of traumatic brain injury and 50.7% of those seen after the 6-week mark. Irrespective of whether they were early or late presenters to our clinic, patients with migraine phenotype (MPTH) took longer to recover from traumatic brain injury than those with posttraumatic headache (PTH) alone. Log rank test indicated that the survival (ie, recovery) distributions between those with migraine phenotype posttraumatic headache (MPTH) and those with posttraumatic headache (PTH) were statistically different, χ2(3) = 50.186 (P < .001). Conclusions: Early identification of migraine phenotype posttraumatic headache (MPTH) following concussion can help guide more effective treatment of headache in traumatic brain injury and provide a road map for the trajectory of recovery from traumatic brain injury symptoms. It will also help us understand better the mechanisms that underlie conversion to persistent posttraumatic headache and chronic migraine after traumatic brain injury.

PMID:35656769 | DOI:10.1177/08830738221100327

J Telemed Telecare. 2022 Jun 3:1357633X221102264. doi: 10.1177/1357633X221102264. Online ahead of print.

ABSTRACT

INTRODUCTION: Traumatic brain injury (TBI) represents a major cause of death and disability worldwide. Brain damage is associated with physical and psychological difficulties among TBI survivors. Diverse face-to-face and telehealth programs exist to help survivors cope with these burdens. However, the effectiveness of telehealth interventions among TBI survivors remains inconclusive.

METHODS: A systematic review and meta-analysis of randomized control trials were conducted. Relevant full-text articles were retrieved from seven databases, from database inception to January 2022, including Academic Search Complete, CINAHL, EMBASE, Cochrane, MEDLINE, PubMed, and Web of Science. Bias was assessed with the revised Cochrane risk-of-bias tool for randomized trials. A meta-analysis was performed using a random-effects model to calculate the pooled effect size of telehealth interventions for TBI survivors. STATA 16.0 was used for statistical analysis.

RESULTS: In total, 17 studies (N = 3158) applying telehealth interventions among TBI survivors were included in the analysis. Telehealth interventions decreased neurobehavioural symptom (standardized mean difference: -0.13; 95% confidence interval [CI]: -0.36 to 0.10), reduce depression (standardized mean difference: -0.32; 95% CI: -0.79 to 0.14), and increase symptom management self-efficacy (standardized mean difference: 0.22; 95% CI: 0.02-0.42).

DISCUSSION: Telehealth interventions are promising avenues for healthcare delivery due to advances in technology and information. Telehealth programs may represent windows of opportunity, combining traditional treatment with rehabilitation to increase symptom management self-efficacy among TBI patients during recovery. Future telehealth programs can focus on developing the contents of telehealth modules based on evidence from this study.

PMID:35656767 | DOI:10.1177/1357633X221102264