Nevin Manimala

Acta Neurol Scand. 2022 Jul 15. doi: 10.1111/ane.13669. Online ahead of print.

ABSTRACT

OBJECTIVES: Unbiased and full disclosure of trial results is vital to evidence-based medicine. Non-publication and selective publication leads to publication bias and unrealistic risk-benefit ratio. In the present study, we aim to determine the publication rate of clinical trials related to neurology registered with the Clinical Trial Registry of India (CTRI), compare the characteristics of published and unpublished trials, and evaluate the adherence of investigators to ethics-approved criteria and outcomes.

MATERIALS AND METHODS: A cross-sectional search using the keyword “neurology” was carried out in CTRI registry. Two independent investigators searched Pubmed, Medline, Scopus, and Google Scholar for published manuscripts. The final literature search occurred in November 2021.

RESULTS: Out of 325 trials, 102 trials were published (31.4%). Ninety-one trials were beyond 3 years of expected time of trial completion and were still unpublished. Randomized trials had a slightly higher publication rate than non-randomized ones (56% vs. 46%, p = .223); however the difference was not statistically significant. Majority of trials sponsored by pharmaceutical companies were not published, while majority of those sponsored by non-pharmaceutical institutions were published (34.5% vs. 69.3%, p < .001). Feedback to CTRI about trial status was particularly poor (31.5% – informed vs. 68.5% – not informed, p < .001). 52 (50.9%) and 65 (63.7%) of the 102 published trials had changed the registered inclusion and exclusion criteria, respectively, in the CTRI registry compared to those in the published manuscript. In 29 (28.3%) of the 102 trials, the primary outcome did not match with that registered in the CTRI and in 73 (57.8%) trials, the secondary outcomes did not match.

CONCLUSION: A large proportion of neurology registered trials are still unpublished, with a majority of pharmaceutical company-sponsored trials not being published. There is scope for improving the provisions in CTRI for enlisting trial results, that may prevent publication bias and also ensure the investigators adhere to the pre-specified ethics approved trial procedures and outcomes.

PMID:35841133 | DOI:10.1111/ane.13669

Res Synth Methods. 2022 Jul 15. doi: 10.1002/jrsm.1592. Online ahead of print.

ABSTRACT

Meta-analysis is a widely used methodology to combine evidence from different sources examining a common research phenomenon, to obtain a quantitative summary of the studied phenomenon. In the medical field, multiple studies investigate the effectiveness of new treatments and meta-analysis is largely performed to generate the summary (average) treatment effect. In the meta-analysis of aggregate continuous outcomes measured in a pretest-posttest design using differences in means as the effect measure, a plethora of methods exist: analysis of final (follow-up) scores, analysis of change scores and analysis of covariance (ANCOVA). Specialised and general purpose statistical software is used to apply the various methods, yet, often the choice among them depends on data availability and statistical affinity. We present a new web-based tool, MA-cont:pre/post effect size, to conduct meta-analysis of continuous data assessed pre- and post-treatment using the aforementioned approaches on aggregate data and a more flexible approach of generating and analysing pseudo individual participant data (IPD). The interactive web environment, available by R Shiny, is used to create this free-to-use statistical tool, requiring no programming skills by the users. A basic statistical understanding of the methods running in the background is a prerequisite and we encourage the users to seek advice from technical experts when necessary. This article is protected by copyright. All rights reserved.

PMID:35841123 | DOI:10.1002/jrsm.1592

Canine Med Genet. 2022 Jul 15;9(1):10. doi: 10.1186/s40575-022-00122-9.

ABSTRACT

Lymphoma is the second most common cancer affecting Golden Retrievers and is hypothesized to arise through a complex interaction of genetic and environmental factors. The aim of this nested case-control study was to investigate the association between potential environmental pollutant sources and lymphoma risk among Golden Retrievers participating in the Golden Retriever Lifetime Study. Forty-nine Golden Retrievers with non-cutaneous lymphoma and 98 Golden Retrievers without a history of cancer matched by age, sex and neuter status were selected from the Golden Retriever Lifetime Study cohort. Geographic proximity between each dog’s primary residence and nine potential sources of environmental pollution was determined. In addition, the average annual ozone and airborne fine particulate matter levels for each dog’s county of residence and owner-reported secondhand smoke exposure were evaluated. Environmental pollution sources of interest included chemical plants, municipal dumps, manufacturing plants, incineration plants, railroad embankment tracks, landfills, coal plants, high-voltage transmission lines, and nuclear power plants. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each exposure of interest. Subgroup analyses were conducted to evaluate whether associations differed among 1) dogs with multicentric lymphoma, 2) dogs with B-cell lymphoma, and 3) dogs with T-cell lymphoma. No variables reached statistical significance when evaluating all cases together. However, cumulative exposure burden (household proximity to 3 or more pollution sources) approached significance within the multicentric lymphoma subgroup (OR = 2.60, 95%CI 0.99-6.86, p-value = 0.053). Patterns emerged among B- and T-cell subgroups, but none reached statistical significance. Ongoing research is warranted to discern if different environmental mechanisms may be driving B- and T-cell lymphoma immunophenotypes, consistent with previously reported regional differences in subtype prevalence.

PMID:35841115 | DOI:10.1186/s40575-022-00122-9

Subst Abuse Treat Prev Policy. 2022 Jul 15;17(1):52. doi: 10.1186/s13011-022-00481-3.

ABSTRACT

BACKGROUND: In recent years, female drinking has been on the rise worldwide, and this trend can be observed in Korea as well. Accordingly, this study aimed to examine the heterogeneous longitudinal changes in drinking patterns among Korean women, while also exploring the determinants of these changes. In particular, the study identified the gender perspective-related determinants of the classified patterns of problem drinking.

METHODS: Data on 4615 adult women who participated in the Korea Welfare Panel Study (KOWEPS) for 3 years (2018-2020) were analyzed longitudinally using SPSS Statistics 22.0 and M-plus 7.0. The changes in female drinking patterns were analyzed using latent class growth analysis. Subsequently, multinomial logistic regression analysis was performed to identify the predictive factors affecting the changes in drinking patterns.

RESULTS: Latent class analysis yielded three classes: “low problem drinking/decreased,” “moderate problem drinking/maintained,” and “high problem drinking/increased.” Of the participants, 80.4% were in the first class, 14.5% in the second, and 5.1% in the third. After controlling for sociodemographic and psychosocial factors, we found: i) domestic violence, work-family balance stress, and gender role perception were not statistically significant for the “moderate problem drinking/maintained” class; lower levels of depression (odds ratio; OR = .750, p < .05) and higher levels of satisfaction with social relationships (OR = 1.257, p < .05) increased the probability of belonging to the “moderate problem drinking/maintained” group compared to the low problem drinking/decreased class; ii) in the “high problem drinking/increased” class, relative to the low problem drinking/decreased class, experience of domestic violence (OR = 1.857, p < .05), work-family balance stress (OR = 1.309, p < .05), and gender role perception (OR = .705, p < .05) were significant predictors of drinking behavior.

CONCLUSIONS: Problem drinking in Korean women demonstrated heterogeneous patterns of change, with gender-specific factors being the main predictors of this change. Therefore, this study developed a strategy for reducing the harmful effects of female drinking, which considers the characteristics of the changes in women’s drinking patterns as well as factors from the gender perspective.

PMID:35841103 | DOI:10.1186/s13011-022-00481-3

Anesth Analg. 2022 Aug 1;135(2):406-413. doi: 10.1213/ANE.0000000000006102. Epub 2022 Jun 3.

ABSTRACT

BACKGROUND: An important variable in the operating room is the nonoperative time (NOT), the time between skin closure on a previous case and skin incision on the following case. Mismanagement of NOT can result in significant financial losses and delays in the operating room (OR) schedule, which can negatively impact efficiency and patient, surgeon, and staff satisfaction. NOT includes general anesthesia induction time (IT), emergence time (ET), and turnover time (TOT), and can be calculated by adding the 3 components. OR efficiency can be increased by applying parallel processing for general anesthesia induction and OR cleaning and reversal of neuromuscular blockade with sugammadex to reduce the 3 components of NOT without compromising patient safety.

METHODS: This is a prospective, randomized study of 111 patients 18 to 75 years of age, American Society of Anesthesiologists (ASA) I-III, undergoing surgery requiring general anesthesia and muscle relaxation. Patients were randomly assigned to the control group (traditional linear processing for induction of anesthesia and OR cleaning and neuromuscular blockade reversal with neostigmine/glycopyrrolate) and the active group (parallel processing for induction of anesthesia and OR cleaning and neuromuscular blockade reversal with sugammadex). The primary outcome measured is the difference in the NOT. The secondary outcomes are surgeon and patient satisfaction.

RESULTS: NOT was significantly shorter in patients who underwent the parallel processing strategy and received sugammadex compared to the patients in the control group (25.0 [18.0-44.0] vs 48.0 [40.0-64.5] minutes; Cliff’ delta = 0.57; P < .001). After excluding the cases in the experimental group that were put into sleep in the OR (ie, the first case of the room), IT, ET, TOT, and NOT were further reduced and remained statistically significantly lower than the control group. Satisfaction scores from surgeons were significantly higher in the active group than in the control group (P < .001). There was no significant difference in the satisfaction scores of patients between the 2 groups.

CONCLUSIONS: Our study showed that interventions, such as parallel processing during induction of anesthesia and room cleaning instead of linear processing and the use of the faster-acting sugammadex instead of the combination of neostigmine and glycopyrrolate for the reversal of rocuronium-induced neuromuscular blockade, resulted in shorter IT, ET, TOT, and therefore NOT, in addition to higher surgeon’s satisfaction.

PMID:35839499 | DOI:10.1213/ANE.0000000000006102

Biom J. 2022 Jul 15. doi: 10.1002/bimj.202100309. Online ahead of print.

ABSTRACT

False discovery rates are routinely controlled by application of the Benjamini-Hochberg step-up procedure to a set of p-values. A method is demonstrated for representing the values so obtained (the BH-FDRs) on a quantile-quantile (Q-Q) plot of the p-values transformed to the negative-logarithmic scale. Recognition of this connection between the BH-FDR and the Q-Q plot facilitates both understanding of the meaning of the BH-FDR and interpretation of the BH-FDR in a particular data set.

PMID:35839474 | DOI:10.1002/bimj.202100309

Cancer Epidemiol Biomarkers Prev. 2022 Jul 15:EPI-21-1451. doi: 10.1158/1055-9965.EPI-21-1451. Online ahead of print.

ABSTRACT

BACKGROUND: Evaluations of cancer etiology and safety and effectiveness of cancer treatments are predicated on large numbers of patients with sufficient baseline and follow-up data. To assess feasibility of FDA’s Sentinel System’s electronic healthcare data for surveillance of malignancy onset and examination of product safety, this study examined patterns of enrollment surrounding new-onset cancers.

METHODS: Using a retrospective cohort of patients based on administrative claims, we identified incident events of 19 cancers among 292.5 million health plan members from January 2000 through February 2020 using International Classification of Diseases (ICD) diagnosis codes. Annual incident cases were stratified by sex, age, medical and drug coverage, and insurer type. Descriptive statistics were calculated for observable time prior to and following diagnosis.

RESULTS: We identified 10,697,573 incident cancer events among members with medical coverage. When drug coverage was additionally required, number of incident cancers was reduced by 41%. Medicare data contributed 61% of cases, with similar duration trends as other insurers. Mean duration of follow-up prior to diagnosis ranged from 4.0-4.6 years, while follow-up post diagnosis ranged from 1.1-3.3 years. Approximately a third (36.1%) had at least 2 years both prior to and following diagnosis.

CONCLUSIONS: The FDA Sentinel System’s electronic healthcare data may be useful for characterizing relatively short latency cancer risk, examining cancer drug utilization and safety post diagnosis, and conducting surveillance for acute adverse events among patients with cancers.

IMPACT: A national distributed system with electronic health data, the Sentinel system provides opportunity for rapid pharmacoepidemiologic assessments relevant in oncology.

PMID:35839466 | DOI:10.1158/1055-9965.EPI-21-1451

Blood. 2022 Jul 15:blood.2022015478. doi: 10.1182/blood.2022015478. Online ahead of print.

ABSTRACT

Here we report the first comparative analysis of patient-reported outcomes (PROs) with chimeric antigen receptor T-cell therapy versus standard-of-care (SOC) therapy in second-line relapsed/refractory large B-cell lymphoma (R/R LBCL) from the pivotal randomized phase 3 ZUMA-7 (NCT03391466) study of axicabtagene ciloleucel (axi-cel) versus SOC. PRO instruments were administered at baseline, day 50, day 100, day 150, month 9, and every 3 months from randomization until 24 months or an event-free survival event. The quality of life (QoL) analysis set comprised patients with a baseline and ≥1 follow-up PRO completion. Prespecified hypotheses for QLQ-C30 Physical Functioning, Global Health Status/QoL, and EQ-5D-5L visual analogue scale (VAS) were tested using mixed-effect models with repeated measures. Clinically meaningful changes were defined as 10 points for QLQ-C30 and 7 for EQ-5D-5L VAS. Among 359 patients, 296 (165 axi-cel, 131 SOC) met inclusion criteria for QoL analysis. At day 100, statistically significant and clinically meaningful differences in mean change of scores from baseline were observed favoring axi-cel over SOC for QLQ-C30 Global Health Status/QoL (estimated difference 18.1 [95% CI, 12.3-23.9]), Physical Functioning (13.1 [95% CI, 8.0-18.2]), and EQ-5D-5L VAS (13.7 [95% CI, 8.5-18.8]; P<.0001 for all). At day 150, scores significantly favored axi-cel versus SOC for Global Health Status/QoL (9.8 [95% CI, 2.6-17.0]; P=.0124) and EQ-5D-5L VAS (11.3 [95% CI, 5.4-17.1]; P=.0004). Axi-cel showed clinically meaningful improvements in QoL over SOC. Superior clinical outcomes and favorable patient experience with axi-cel should help inform treatment choices in second-line R/R LBCL.

PMID:35839452 | DOI:10.1182/blood.2022015478

J Clin Oncol. 2022 Jul 15:JCO2102707. doi: 10.1200/JCO.21.02707. Online ahead of print.

ABSTRACT

PURPOSE: Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression-based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis.

MATERIALS AND METHODS: We assembled a well-characterized PTCL training cohort (n = 105) with gene expression profiling data to derive a diagnostic signature using fresh-frozen tissue on the HG-U133plus2.0 platform (Affymetrix, Inc, Santa Clara, CA) subsequently validated using matched FFPE tissues in a digital gene expression profiling platform (nCounter, NanoString Technologies, Inc, Seattle, WA). Statistical filtering approaches were applied to refine the transcriptomic signatures and then validated in another PTCL cohort (n = 140) with rigorous pathology review and ancillary assays.

RESULTS: In the training cohort, the refined transcriptomic classifier in FFPE tissues showed high sensitivity (> 80%), specificity (> 95%), and accuracy (> 94%) for PTCL subclassification compared with the fresh-frozen-derived diagnostic model and showed high reproducibility between three independent laboratories. In the validation cohort, the transcriptional classifier matched the pathology diagnosis rendered by three expert hematopathologists in 85% (n = 119) of the cases, showed borderline association with the molecular signatures in 6% (n = 8), and disagreed in 8% (n = 11). The classifier improved the pathology diagnosis in two cases, validated by clinical findings. Of the 11 cases with disagreements, four had a molecular classification that may provide an improvement over pathology diagnosis on the basis of overall transcriptomic and morphological features. The molecular subclassification provided a comprehensive molecular characterization of PTCL subtypes, including viral etiologic factors and translocation partners.

CONCLUSION: We developed a novel transcriptomic approach for PTCL subclassification that facilitates translation into clinical practice with higher precision and uniformity than conventional pathology diagnosis.

PMID:35839444 | DOI:10.1200/JCO.21.02707

JCO Glob Oncol. 2022 Jul;8:e2200131. doi: 10.1200/GO.22.00131.

ABSTRACT

PURPOSE: In describing our ten-year experience with treating chronic myeloid leukemia (CML) as part of the Glivec Patient Assistance Program (GIPAP) in rural Rwanda, we evaluate (1) patient characteristics and treatment outcomes, (2) resource-adapted management strategies, and (3) the impact of diagnostic capacity development.

METHODS: We retrospectively reviewed all patients with BCR-ABL-positive CML enrolled in this GIPAP program between 2009 and 2018. Clinical data were analyzed using descriptive statistics, Kaplan-Meier methods, proportional hazards regression, and the Kruskal-Wallis test.

RESULTS: One hundred twenty-four patients were included. The median age at diagnosis was 34 (range 8-81) years. On imatinib, 91% achieved complete hematologic response (CHR) after a median of 49 days. Seven (6%) and 12 (11%) patients had primary and secondary imatinib resistance, respectively. The 3-year overall survival was 80% (95% CI, 72 to 87) for the cohort, with superior survival in imatinib responders compared with those with primary and secondary resistance. The median time from imatinib initiation to CHR was 59 versus 38 days (P = .040) before and after in-country diagnostic testing, whereas the median time to diagnosis (P = .056) and imatinib initiation (P = .170) was not significantly different.

CONCLUSION: Coupling molecular diagnostics with affordable access to imatinib within a comprehensive cancer care delivery program is a successful long-term strategy to treat CML in resource-constrained settings. Our patients are younger and have higher rates of imatinib resistance compared with historic cohorts in high-income countries. High imatinib resistance rates highlight the need for access to molecular monitoring, resistance testing, and second-generation tyrosine kinase inhibitors, as well as systems to support drug adherence. Hematologic response is an accurate resource-adapted predictor of survival in this setting. Local diagnostic capacity development has allowed for continuous, timely CML care delivery in Rwanda.

PMID:35839427 | DOI:10.1200/GO.22.00131