Nevin Manimala

Aust N Z J Psychiatry. 2023 Dec 21:48674231218623. doi: 10.1177/00048674231218623. Online ahead of print.

ABSTRACT

OBJECTIVE: We evaluated the presence and impact of unblinding during the influential Treatment for Adolescents with Depression Study (ClinicalTrials.gov Identifier: NCT00006286).

METHOD: Our analysis was part of a Restoring Invisible and Abandoned Trials reanalysis. Treatment for Adolescents with Depression Study trialled fluoxetine, placebo, cognitive behaviour therapy or their combination, in treating adolescents with major depressive disorder. We analysed the accuracy of guesses of fluoxetine or placebo allocation, and their effects on change in Children’s Depression Rating Scale-Revised at 12 weeks.

RESULTS: Of 221 participants allocated to fluoxetine or placebo, 151 adolescents (68%) had their guess about pill-treatment-arm allocation recorded at week 6, and guesses were recorded for 154 independent evaluators, 159 parents and 164 pharmacotherapists. All of these groups guessed treatment allocation more accurately than would be expected by chance (60-66% accuracy; all p-values ⩽ 0.004). Guesses did not become more accurate between 6 and 12 weeks and were not predicted by adverse events, though event documentation was poor. Treatment guess had a substantial and statistically significant effect on outcome (Children’s Depression Rating Scale-Revised change mean difference 9.12 [4.69; 13.55], β = 0.334, p < 0.001), but actual treatment arm did not (1.53 [-2.83; 5.89], β = 0.056, p = 0.489). Removing guess from the analysis increased the apparent effect of treatment arm, making it almost statistically significant at the conventional alpha-level of 0.05 (p = 0.06).

CONCLUSIONS: For Treatment for Adolescents with Depression Study, treatment guesses strongly predicted outcomes and may have led to the exaggeration of drug effectiveness in the absence of actual effects. The integrity of double-blinding in trials should be routinely assessed and reported.

PMID:38126083 | DOI:10.1177/00048674231218623

Front Med (Lausanne). 2023 Dec 6;10:1296751. doi: 10.3389/fmed.2023.1296751. eCollection 2023.

ABSTRACT

INTRODUCTION: The purpose of this study is to systematically evaluate the efficacy and safety of acupuncture combined with pelvic floor rehabilitation training in the treatment of postpartum stress urinary incontinence, and to promote the further promotion and application of acupuncture in the field of rehabilitation.

METHODS AND ANALYSIS: Randomized controlled trials (RCTs) of acupuncture combined with pelvic floor rehabilitation in the treatment of postpartum stress urinary incontinence will be searched in PubMed, Web of Science (WOS), Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang (WF), and VIP databases. The clinical trial Registry (ClinicalTrials.gov and Chinese clinical trial Registry) will also be searched. The search period is limited to July 1, 2023, and the language limit of this systematic review is Chinese and English. The primary outcome is clinical effective rate. International Consultation on Incontinence Questionnaire-Short Form (ICI-Q-SF), 1-h pad test, pelvic floor muscle potential value, incidence of adverse events are secondary outcomes. A meta-analysis will be performed using RevMan 5.4 statistical software. If feasible, subgroup analysis and sensitivity analysis will be performed to address potential causes of inconsistency and heterogeneity. The risk of bias will be assessed using the approach recommended by Cochrane Handbook for Systematic Reviews of Interventions, and the quality of evidence will be assessed using GRADE. This Protocol has been developed in accordance with the guideline of Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015.

DISCUSSION: Acupuncture combined with pelvic floor rehabilitation training can effectively promote the rehabilitation of postpartum stress urinary incontinence patients, and provide a reference for the clinical application of integrated Chinese and Western medicine treatment in the field of rehabilitation.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023455801.

PMID:38126072 | PMC:PMC10730657 | DOI:10.3389/fmed.2023.1296751

Front Med (Lausanne). 2023 Dec 6;10:1268846. doi: 10.3389/fmed.2023.1268846. eCollection 2023.

ABSTRACT

BACKGROUND: The progression of early stage non-small cell lung cancer (NSCLC) is closely related to epidermal growth factor receptor (EGFR) mutation status. The purpose of this study was to systematically investigate the relationship between EGFR mutation status and demographic, imaging, and ultimately pathologic features in patients with NSCLC.

METHODS: A complete literature search was conducted using the PubMed, Web of Science, EMBASE, and Cochrane Library databases to discover articles published by May 15, 2023 that were eligible. The relationship between EGFR mutation status and specific demographic, imaging, and ultimately pathologic features in patients with NSCLC was evaluated using pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The standardized mean difference (SMD) with 95% CIs was the appropriate statistic to summarize standard deviations (SDs) means for continuous variables.

RESULTS: A total of 9 studies with 1789 patients were included in this analysis. The final findings suggested that patients with a greater age, female gender, and non-smoking status would have a relatively higher incidence of EGFR mutations. Additionally, the risk of EGFR mutations increased with larger tumor diameter, tumor imaging presentation of mixed ground glass opacity (mGGO), and tumor pathological findings of minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (IAC). Significantly, malignancies presenting as MIA are more likely to contain L858R point mutations (OR = 1.80; 95% CI: 1.04-3.13; p = 0.04) rather than exon 19 deletions (OR = 1.81; 95% CI: 0.95-3.44; p = 0.07).

CONCLUSION: This meta-analysis showed that imaging parameters and histological classifications of pulmonary nodules may be able to predict stage IA NSCLC genetic changes.

PMID:38126071 | PMC:PMC10731050 | DOI:10.3389/fmed.2023.1268846

R Soc Open Sci. 2023 Dec 20;10(12):230621. doi: 10.1098/rsos.230621. eCollection 2023 Dec.

ABSTRACT

Disease spread can be affected by pharmaceutical interventions (such as vaccination) and non-pharmaceutical interventions (such as physical distancing, mask-wearing and contact tracing). Understanding the relationship between disease dynamics and human behaviour is a significant factor to controlling infections. In this work, we propose a compartmental epidemiological model for studying how the infection dynamics of COVID-19 evolves for people with different levels of social distancing, natural immunity and vaccine-induced immunity. Our model recreates the transmission dynamics of COVID-19 in Ontario up to December 2021. Our results indicate that people change their behaviour based on the disease dynamics and mitigation measures. Specifically, they adopt more protective behaviour when mandated social distancing measures are in effect, typically concurrent with a high number of infections. They reduce protective behaviour when vaccination coverage is high or when mandated contact reduction measures are relaxed, typically concurrent with a reduction of infections. We demonstrate that waning of infection and vaccine-induced immunity are important for reproducing disease transmission in autumn 2021.

PMID:38126062 | PMC:PMC10731327 | DOI:10.1098/rsos.230621

R Soc Open Sci. 2023 Dec 20;10(12):230574. doi: 10.1098/rsos.230574. eCollection 2023 Dec.

ABSTRACT

The relationship between music and emotion has been addressed within several disciplines, from more historico-philosophical and anthropological ones, such as musicology and ethnomusicology, to others that are traditionally more empirical and technological, such as psychology and computer science. Yet, understanding the link between music and emotion is limited by the scarce interconnections between these disciplines. Trying to narrow this gap, this data-driven exploratory study aims at assessing the relationship between linguistic, symbolic and acoustic features-extracted from lyrics, music notation and audio recordings-and perception of emotion. Employing a listening experiment, statistical analysis and unsupervised machine learning, we investigate how a data-driven multi-modal approach can be used to explore the emotions conveyed by eight Bach chorales. Through a feature selection strategy based on a set of more than 300 Bach chorales and a transdisciplinary methodology integrating approaches from psychology, musicology and computer science, we aim to initiate an efficient dialogue between disciplines, able to promote a more integrative and holistic understanding of emotions in music.

PMID:38126059 | PMC:PMC10731325 | DOI:10.1098/rsos.230574

Oncoimmunology. 2023 Oct 30;12(1):2261264. doi: 10.1080/2162402X.2023.2261264. eCollection 2023.

ABSTRACT

Patients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus monotherapy in cancer patients with pAIDs. The primary outcome was time to AEs (immune-related adverse events (irAEs) and/or pAID flares), with progression-free survival (PFS) and overall survival as secondary outcomes. Sixty-four of 133 patients (48%) received ICI combination and 69 (52%) monotherapy. Most had melanoma (32%) and lung cancer (31%). Most common pAIDs were rheumatic (28%) and dermatologic (23%). Over a median follow-up of 15 months (95%CI, 11-18 mo), the cumulative incidence of any-grade irAEs was higher for combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.27, 95%CI 1.35-3.82). No statistically significant difference was observed in high-grade irAEs (sHR 2.31 (0.95-5.66), P = .054) or the cumulative incidence of pAID flares. There was no statistically significant difference for melanoma PFS between combination versus monotherapy (23.2 vs. 17.1mo, P = .53). The combination group was more likely to discontinue or hold ICI, but > 50% of the combination group was still able to continue ICI therapy. No treatment-related deaths occurred. In our cohort with pAIDs, patients had a tolerable toxicity profile with ICI combination therapy. Our results support the use of ICI combination if deemed necessary for cancer therapy in patients with pAIDs, since the ICI toxicities were comparable to monotherapy, able to be effectively managed and mostly did not require ICI interruption.

PMID:38126033 | PMC:PMC10732692 | DOI:10.1080/2162402X.2023.2261264

Oncoimmunology. 2023 Nov 27;12(1):2284483. doi: 10.1080/2162402X.2023.2284483. eCollection 2023.

ABSTRACT

The human Epstein-Barr virus (EBV), as a member of the human γ herpes viruses (HHV), is known to be linked with distinct tumor types. It is a double-stranded DNA virus and its genome encodes among others for 48 different microRNAs (miRs). Current research demonstrated a strong involvement of certain EBV-miRs in molecular immune evasion mechanisms of infected cells by, e.g., the disruption of human leukocyte antigen (HLA) class Ia and NKG2D functions. To determine novel targets of EBV-miRs involved in immune surveillance, ebv-miR-BART7-3p, an EBV-encoded miR with high expression levels during the different lytic and latent EBV life cycle phases, was overexpressed in human HEK293T cells. Using a cDNA microarray-based comparative analysis, 234 (229 downregulated and 5 upregulated) deregulated human transcripts were identified in ebv-miR-BART7-3p transfectants, which were mainly involved in cellular processes and molecular binding. A statistically significant downregulation of the anti-proliferative and tumor-suppressive hsa-miR-34A and the anti-viral interferon lambda (IFNL)3 mRNA was found. The ebv-miR-BART7-3p-mediated downregulation of IFNL3 expression was due to a direct interaction with the IFNL3 3′-untranslated region (UTR) as determined by luciferase reporter gene assays including the identification of the accurate ebv-miR-BART7-3p binding site. The effect of ebv-miR-BART7-3p on the IFNL3 expression was validated both in human cell lines in vitro and in human tissue specimen with known EBV status. These results expand the current knowledge of EBV-encoded miRs and their role in immune evasion, pathogenesis and malignant transformation.

PMID:38126030 | PMC:PMC10732682 | DOI:10.1080/2162402X.2023.2284483

Clin Epidemiol. 2023 Dec 16;15:1193-1206. doi: 10.2147/CLEP.S434829. eCollection 2023.

ABSTRACT

PURPOSE: To evaluate the new Clinical Practice Research Datalink (CPRD) Aurum database, we estimated ‘correctness’ (ie accuracy, validity) and ‘completeness’ (ie presence, missingness) of malignant breast cancer diagnoses recorded in CPRD Aurum compared to external linked data sources: Hospital Episode Statistics (HES) Admitted Patient Care (APC), HES Outpatient (OP), and Cancer Registry (CR), and to the previously validated CPRD GOLD.

METHODS: Linkage-eligible, female patients with incident malignant breast cancer diagnosis recorded in at least one study data source were selected. Correctness was the proportion of malignant breast cancer cases recorded in CPRD Aurum or GOLD who also had a diagnosis recorded in HES APC/OP (2004-2019) or CR (2004-2016). Completeness was estimated by identifying all malignant breast cancer diagnoses in HES APC/OP or CR and calculating the proportion with a concordant diagnosis in CPRD Aurum or GOLD.

RESULTS: Compared to HES APC/OP, there were 85,659 and 31,452 eligible patients in CPRD Aurum and GOLD, respectively. Correctness estimates were high (CPRD Aurum 83.5%, GOLD 81.7%). Compared to CR, there were 70,190 and 29,597 eligible patients in CPRD Aurum and GOLD, respectively: correctness was 89.1% for CPRD Aurum and 88.2% for GOLD. Completeness estimates for CPRD Aurum and GOLD were high (>90%). Diagnoses were recorded in CPRD Aurum within -7 to 74 days of those in the linked sources. Reasons for discordant diagnostic coding included presence of treatment or other clinical codes only, diagnosis coded after end of follow-up, non-malignant breast cancer in linked data, and administrative codes in lieu of diagnostic codes.

CONCLUSION: These results indicate that correctness and completeness of malignant breast cancer diagnoses in CPRD Aurum were high and similar to CPRD GOLD. This provides confidence in use of CPRD Aurum for research purposes. Where complete case capture is important, researchers should consider linkage to HES APC or CR.

PMID:38126002 | PMC:PMC10731987 | DOI:10.2147/CLEP.S434829

Front Reprod Health. 2023 Dec 6;5:1286920. doi: 10.3389/frph.2023.1286920. eCollection 2023.

ABSTRACT

INTRODUCTION: United States consumers spend over two billion dollars a year on intimate care products. These products, along with scented menstrual products, are marketed for odor control, perceived “freshness,” and vaginal/vulvar cleanliness. However, these scent-altering products may increase exposure to carcinogenic and endocrine-disrupting chemicals. Prior research has not adequately characterized demographic differences in product use. The objective of our study is to examine racial/ethnic and educational differences in menstrual and intimate care product use among people who menstruate.

METHODS: We pooled data from two US-based cross sectional studies to examine demographic characteristics and product use in 661 participants aged 18-54 years. Participants reported use of scented and unscented menstrual products (tampons, sanitary pads, and menstrual cups) and intimate care products (vaginal douches, sprays, wipes, and powders). We examined differences by race/ethnicity and education using log-binomial regression and latent class analysis (LCA), which can identify groups based on product use patterns.

RESULTS: Our sample was 33.4% Black, 30.9% Latina, 18.2% White, and 16.2% another identity. Approximately half the population had a bachelor’s degree or more; 1.4% identified as transgender and 1.8% as non-binary. In adjusted models, scent-altering products (i.e., scented menstrual and intimate care products) were more likely to be used by those with less formal education (p < 0.05). Unscented menstrual products were more likely to be used by those with more formal education. Compared to Black participants, White participants were more likely to use unscented tampons and menstrual cups and less likely to use douches and wipes (p < 0.05). Using LCA we identified two groups: one more likely to use scent-altering products, and a second more likely to use unscented menstrual products. Less education and older age, but not race/ethnicity, was significantly associated with membership in the group more likely to use scent-altering products. While sex/gender composition did not statistically vary across groups, all non-binary participants fell in the unscented menstrual product group.

DISCUSSION: Lower educational attainment was consistently associated with greater use of scent-altering menstrual and intimate care products. Future research should examine associations between body odor stigma, product use, and health risks at intersections of race, class, and gender.

PMID:38126001 | PMC:PMC10731462 | DOI:10.3389/frph.2023.1286920

BMC Cancer. 2023 Dec 20;23(1):1258. doi: 10.1186/s12885-023-11712-6.

ABSTRACT

BACKGROUND: There is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT).

METHODS: Patients aged 0-39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed.

RESULTS: Two hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6-39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P < 0.0001]. DH/DE status was an independent adverse predictor of PFS in multivariate analysis (HR 5.8, p = 0.03). Ten patients (4.5%) (all aged > 25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0-196.6) months after ASCT, and SPM was the cause of death in five (50%) of them.

CONCLUSIONS: CAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS.

PMID:38124057 | DOI:10.1186/s12885-023-11712-6