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The Economic Benefit of Remission for Patients with Rheumatoid Arthritis

Rheumatol Ther. 2022 Jul 14. doi: 10.1007/s40744-022-00473-6. Online ahead of print.

ABSTRACT

INTRODUCTION: In patients with rheumatoid arthritis (RA), attaining remission or low disease activity (LDA), as recommended by the treat-to-target approach, has shown to yield improvement in symptoms and quality of life. However, limited evidence from real-world settings is available to support the premise that better disease control is associated with lower healthcare costs. This study fills in evidence gaps regarding the cost of care by RA disease activity (DA) states and by therapy.

METHODS: This retrospective cohort study linked medical and prescription claims from Optum Clinformatics Data Mart to electronic health record data from Illumination Health over 1/1/2010-3/31/2020. Mean annual costs for payers and patients were examined, stratifying on DA state and baseline use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics, and targeted synthetic (ts)DMARDs. Subgroup analysis examining within-person change in costs pre- and post-initiation of new therapy was also performed. Descriptive statistics, means, and boot-strapped confidence intervals were analyzed by DA state and by RA therapy. Furthermore, multivariate negative binomial regression analysis adjusting for key baseline characteristics was conducted.

RESULTS: Of 2339 eligible patients, 19% were in remission, 40% in LDA, 29% in moderate DA (MDA), and 12% in high DA (HDA) at baseline. Mean annual costs during follow-up were substantially less for patients in remission ($40,072) versus those in MDA ($56,536) and HDA ($59,217). For patients in remission, csDMARD use was associated with the lowest mean annual cost ($25,575), tsDMARD was highest ($75,512), and tumor necrosis factor inhibitor (TNFi) ($69,846) and non-TNFi ($57,507) were intermediate. Among new TNFi (n = 137) and non-TNFi initiators (n = 107), 31% and 26% attained LDA/remission, respectively, and the time to achieve remission/LDA was numerically shorter in TNFi vs. non-TNFi initiators. For those on biologics, mean annual within-person medical and inpatient costs were lower after achieving LDA/remission, although pharmacy costs were higher.

CONCLUSIONS: Cost of care increased with increasing DA state, with patients in remission having the lowest costs. Optimizing DA has the potential for substantial savings in healthcare costs, although may be partially offset by the high cost of targeted RA therapies.

PMID:35834162 | DOI:10.1007/s40744-022-00473-6

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Short-term celecoxib (celebrex) adjuvant therapy: a clinical trial study on COVID-19 patients

Inflammopharmacology. 2022 Jul 14. doi: 10.1007/s10787-022-01029-4. Online ahead of print.

ABSTRACT

BACKGROUND: It is known that severe acute respiratory coronavirus 2 (SARS-CoV-2) is the viral strain responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Current documents have demonstrated that the virus causes a PGE2 storm in a substantial proportion of patients via upregulating cyclooxygenase-2 (COX-2) and downregulating prostaglandin E2 (PGE2)-degrading enzymes within the host cell.

AIM: Herein, we aimed to study how short-term treatment with celecoxib (Celebrex), a selective COX-2 inhibitor, affects demographic features, early symptoms, O2 saturation, and hematological indices of cases with COVID-19.

METHODS: A total of 67 confirmed COVID-19 cases with a mild or moderate disease, who had been referred to an institutional hospital in south-eastern Iran from October 2020 to September 2021, were enrolled. Demographic characteristics, symptoms, and hematological indices of the patients were recorded within different time periods. One-way ANOVA or Kruskal-Wallis tests were used to determine differences between data sets based on normal data distribution.

RESULTS: O2 saturation was statistically different between the control group and patients receiving celecoxib (p = 0.039). There was no marked difference between the groups in terms of the symptoms they experienced (p > 0.05). On the first days following Celebrex therapy, analysis of complete blood counts showed that white blood cell (WBC) counts were markedly lower in patients treated with a high dose of celecoxib (0.4 g/day) than in controls (p = 0.026). However, mean lymphocyte levels in patients receiving a high dose of celecoxib (0.4 g/day) were markedly higher than in patients receiving celecoxib with half of the dose (0.2 g/day) for one week or the untreated subjects (p = 0.004). Changes in platelet count also followed the WBC alteration pattern.

CONCLUSION: Celecoxib is a relatively safe, inexpensive, and widely available drug with non-steroidal anti-inflammatory properties. The therapeutic efficacy of celecoxib depends on the administrated dose. Celecoxib might improve disease-free survival in patients with COVID-19.

PMID:35834150 | DOI:10.1007/s10787-022-01029-4

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Prognostic factors for brain metastasis in women presenting cervical cancer

J Neurooncol. 2022 Jul 14. doi: 10.1007/s11060-022-04082-9. Online ahead of print.

ABSTRACT

PURPOSE: Although rare, brain metastases (BM) from cervical cancer (CC) are highly lethal. Adequate patient selection for specific treatments can improve survival rates in patients afflicted by this condition. This study aimed to describe the characteristics of CC patients who developed BM and overall survival-associated factors. Brain metastasis impact on the overall survival was assessed as a secondary objective.

METHODS: This assessment comprises a retrospective cohort study on 3394 women presenting CC diagnosed between January 2010 and December 2017 at a single referral center. Incident BM cases were included. Descriptive statistics were calculated. Kaplan-Meier curves were used for the survival analysis and a Cox proportional hazards regression model was applied to explore the risk of death according to the analyzed independent variables.

RESULTS: A total of 48 incident BM cases were identified. The median time between CC diagnosis and BM development was 1.5 years. Headaches (29.2%), dizziness/altered balance (29.2%), vertigo (29.2%) and motor disturbances (25.0%) were the most common signs and symptoms at presentation. Median overall survival after BM diagnosis was of 1.6 months (95% CI 0.9-2.3) while in the group of women without BM it was 5.5 years (95% CI 4.9-6.1). Concerning the Cox multivariate analysis, presenting one extracerebral metastases site (HR 2.8; 95% CI 1.3-6.2; p = 0.009) and receiving supportive treatment (HR 13.7; 95% CI 3.1-60.5; p 0.001) were independently associated with the risk of death.

CONCLUSION: The median survival of women with BM following CC was poor. Women without extracerebral metastases and undergoing multimodal treatment displayed better overall survival rates.

PMID:35834147 | DOI:10.1007/s11060-022-04082-9

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An Empirical Attempt to Operationalize Chasing Losses in Gambling Utilizing Account-Based Player Tracking Data

J Gambl Stud. 2022 Jul 14. doi: 10.1007/s10899-022-10144-4. Online ahead of print.

ABSTRACT

In recent years, account-based player tracking data have been utilized as a potential tool to identify problem gambling online and associated markers of harm. One established marker of harm among problem gamblers is chasing losses, and chasing losses is a key criterion for gambling disorder in the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders. Given the paucity of research with respect to chasing losses among online casino players using account-based data, the present study developed five metrics that may be indicative of chasing behavior: These were (i) within-session chasing, (ii) across-session chasing, (iii) across-days chasing, (iv) regular gambling account depletion, and (v) frequent session depositing. The authors were given access by a European online casino to raw data of all players who had placed at least one bet or wagered at least once during December 2021 (N = 16,771 players from the UK, Spain, and Sweden). Results indicated that frequent session depositing reflected chasing losses better than any of the other four metric operationalizations used. While frequent session depositing appears to be more indicative of chasing losses than the other four metrics, all the metrics provide useful information which can be used to help identify problematic gambling behavior online.

PMID:35834118 | DOI:10.1007/s10899-022-10144-4

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RS-FetMRI: a MATLAB-SPM Based Tool for Pre-processing Fetal Resting-State fMRI Data

Neuroinformatics. 2022 Jul 14. doi: 10.1007/s12021-022-09592-5. Online ahead of print.

ABSTRACT

Resting-state functional magnetic resonance imaging (rs-fMRI) most recently has proved to open a measureless window on functional neurodevelopment in utero. Fetal brain activation and connectivity maps can be heavily influenced by 1) fetal-specific motion effects on the time-series and 2) the accuracy of time-series spatial normalization to a standardized gestational-week (GW) specific fetal template space.Due to the absence of a standardized and generalizable image processing protocol, the objective of the present work was to implement a validated fetal rs-fMRI preprocessing pipeline (RS-FetMRI) divided into 6 inter-dependent preprocessing modules (i.e., M1 to M6) and designed to work entirely as an extension for Statistical Parametric Mapping (SPM).RS-FetMRI pipeline output analyses on rs-fMRI time-series sampled from a cohort of fetuses acquired on both 1.5 T and 3 T MRI scanning systems showed increased efficacy of estimation of the degree of movement coupled with an efficient motion censoring procedure, resulting in increased number of motion-uncorrupted volumes and temporal continuity in fetal rs-fMRI time-series data. Moreover, a “structural-free” SPM-based spatial normalization procedure granted a high degree of spatial overlap with high reproducibility and a significant improvement in whole-brain and parcellation-specific Temporal Signal-to-Noise Ratio (TSNR) mirrored by functional connectivity analysis.To our knowledge, the RS-FetMRI pipeline is the first semi-automatic and easy-to-use standardized fetal rs-fMRI preprocessing pipeline completely integrated in MATLAB-SPM able to remove entry barriers for new research groups into the field of fetal rs-fMRI, for both research or clinical purposes, and ultimately to make future fetal brain connectivity investigations more suitable for comparison and cross-validation.

PMID:35834105 | DOI:10.1007/s12021-022-09592-5

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Effect of different irrigation activation techniques on irrigation penetration into the simulated lateral canals

Odontology. 2022 Jul 14. doi: 10.1007/s10266-022-00729-1. Online ahead of print.

ABSTRACT

This study, in which a hundred human teeth with single straight canal were used, focused on the evaluation of contrast solution penetration ability into the simulated lateral canals activated by XP-endo Finisher (XPF), EDDY, Nd:YAG, and Er:YAG laser systems with three different observation methods. The root canals were prepared up to X4 at working length using the ProTaper Next system. The teeth were decalcified and simulated lateral canals were created with #8 K-file at 2, 4, and 6 mm levels. Then the teeth were cleared using methyl salicylate and divided into 5 equal groups according to irrigation activation techniques (CSI, XPF, EDDY, Nd:YAG, and Er:YAG laser). After the contrast solution was activated, images of the simulated lateral canals were obtained by a dental microscope, digital radiography, and CBCT. The contrast solution penetration scores at the 2, 4, and 6 mm levels according to irrigation activation techniques and observation methods were analyzed statistically using Kruskal-Wallis non-parametric analysis of variance Bonferroni test post hoc comparisons. With the other 2 parameters are ignored, the highest and lowest contrast solution penetration were observed at 6 and 2 mm simulated lateral canal levels (p < 0.05), in Er:YAG irrigation activation and CSI technique (p < 0.05), and in direct visual and digital radiographic observation method (p < 0.05), respectively. Within the limits of this study, it was determined that the contrast solution penetration into the simulated lateral canals decreased from the coronal to the apical and achieved with the most effective Er:YAG laser activation technique. In addition, direct visual observation was found to be the best method for the assessment of contrast solution penetration.

PMID:35834067 | DOI:10.1007/s10266-022-00729-1

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The Value of Indirect Comparisons of Systemic Biologics for Psoriasis: Interpretation of Efficacy Findings

Dermatol Ther (Heidelb). 2022 Jul 14. doi: 10.1007/s13555-022-00765-3. Online ahead of print.

ABSTRACT

INTRODUCTION: It can be challenging for dermatologists to keep abreast of the growing evidence from published indirect comparisons (ICs) of treatments for psoriasis. The objective of this analysis was to summarise comparative clinical efficacy and safety findings from ICs of systemic biologics for the treatment of moderate-to-severe psoriasis and to identify factors potentially affecting efficacy outcomes and their possible implications for clinical decision making.

METHODS: An umbrella review of short- and long-term efficacy and safety findings from 26 ICs visually compared 90% improvement in Psoriasis Area Severity Index (PASI90) treatment rankings and three safety outcome rankings side by side. Pearson’s correlation coefficients measured the strength of the association between each pair of ICs on the basis of identified factors that could potentially affect efficacy findings.

RESULTS: Some consistency in short-term PASI90 efficacy rankings was observed for certain drugs, although rankings for most drugs varied by IC. Factors potentially affecting efficacy outcomes included the use of different methodologies for head-to-head comparison and statistical analyses, and variation in drugs and classes included treatment dosing and duration, outcome definitions and effect measures reported between ICs. Considerable variation in these factors was found across all 26 ICs. Comparative safety information of value to physicians was limited.

CONCLUSIONS: Substantial differences were identified between ICs in factors that could potentially affect efficacy outcomes. Treatment rankings must be interpreted alongside actual differences in IC outcomes to allow conclusions on clinical relevance. Drugs within a class cannot be considered of equal efficacy: therapies should be considered individually rather than by class.

PMID:35834062 | DOI:10.1007/s13555-022-00765-3

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Effects of Promove – Saúde da Mulher on anxiety, depression, social skills, and satisfaction: A single-subject design

Psicol Reflex Crit. 2022 Jul 14;35(1):21. doi: 10.1186/s41155-022-00226-y.

ABSTRACT

Terapia Analítico-Comportamental (TAC) (in English, behavioral-analytic therapy, behavior therapy, or clinical behavior analysis) is a possible intervention for cases of anxiety and depression, but it still has much to advance in terms of efficacy and clinical utility evidence. This article aims to describe the effects of a semi-structured intervention in the model of TAC regarding anxiety and depression, behavior, complaints, and satisfaction indicators. Participants included three women with children, marital relationships, and work, aged between 34 and 41 with complaints compatible with anxiety and depression disorders. The intervention used Promove – Saúde da Mulher (PSM) (in English, Promote Women’s Health), which included 17 topics, most of them related to social skills. Instruments included the GAD-7 for anxiety, PHQ-9 for depression, IHS-2 Del Prette for social skills, a Complaints Checklist for monitoring clinical demands, and an Evaluation of the Therapeutic Process to describe clients’ satisfaction rates. The results from the standardized instruments were statistically analyzed via the JT method. All three participants showed reliable improvements in anxiety and/or depression, improvement in most complaints, and satisfaction with the intervention and its outcomes. Acquisition of social skills occurred in two cases. One participant dropped out and another one relapsed at follow-up. The efficacy criteria were used to evaluate the internal validity of the present study. The study collected the first evidences of outcome and satisfaction for PSM, thus enabling future investigations on the efficacy and clinical utility of this intervention program.

PMID:35834063 | DOI:10.1186/s41155-022-00226-y

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Mycophenolate mofetil-induced hypogammaglobulinemia and infectious disease susceptibility in pediatric patients with chronic rheumatic disorders: a monocentric retrospective study

Eur J Pediatr. 2022 Jul 14. doi: 10.1007/s00431-022-04560-2. Online ahead of print.

ABSTRACT

Mycophenolate mofetil (MMF) is an immunosuppressive drug used for the treatment of autoimmune rheumatological diseases. To test the risk of hypothetical drug-induced hypogammaglobulinemia, the aim of this study was to report the trend of the immunoglobulin (Ig) values and of the infectious diseases in children treated with MMF. This study retrospectively evaluated demographic, clinical, and laboratory data of a cohort of patients affected by a chronic rheumatic disease receiving MMF, followed at the Rheumatology Unit of Meyer Children Hospital, Florence. A total of 29 pediatric patients were enrolled. In patients with normal values of immunoglobulins at the baseline, treatment with MMF resulted in a statistically significant reduction of the IgG levels (p = 0.0058) and in a decrease of IgM levels not reaching statistical significance. The levels of IgA were not affected. During the follow-up, seven patients developed an humoral immune defect. The univariate analysis did not identify any risk factors related to the iatrogenic hypogammaglobulinemia. The infection rate during MMF therapy was significantly higher than the 12-month period before therapy (p = 0.006), while the severe infections did not significantly increase (p = 0.1818), even considering only the patients with hypogammaglobulinemia.

CONCLUSION: In pediatric patients with chronic rheumatic diseases, immunological first level tests and serological analyses to screen the protection against the common childhood pathogens are suggested before starting an immunosuppressive drug. These patients should also complete the vaccination schedule. In patients treated with MMF a strict monitoring of Ig is required during treatment and after discontinuation of the drug.

WHAT IS KNOWN: • MMF is an immunosuppressive drug initially used for the treatment of the graft-versus-host disease. • Mycophenolic acid is an inhibitor of inosine-5′-monophosphate dehydrogenase, expressed in lymphocytes; therefore, MMF could impair the immune system function.

WHAT IS NEW: • MMF resulted in a reduction of IgG and an increase of not severe infection rate. • Immunological first level tests, including Ig, lymphocyte subpopulations, and antibody response to vaccines, are suggested in pediatric patients before starting MMF; a strict monitoring of Ig is important before, during, and after MMF treatment.

PMID:35834043 | DOI:10.1007/s00431-022-04560-2

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Comprehensive transcriptomic and co-expression analysis of ABL1 gene and molecularly targeted drugs in hepatocellular carcinoma based on multi-database mining

Med Oncol. 2022 Jul 14;39(10):146. doi: 10.1007/s12032-022-01730-y.

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Consequently, it is essential to identify biomarkers for treatment response and the prognosis prediction. We investigated whether ABL1 can function as a biomarker or a drug target for HCC. We assessed the ABL1 expression, genetic alterations and patients’ survival from LinkedOmics, GEO, TCGA and Human Protein Atlas. We analyzed PPI, GO and KEGG pathways. GSEA was analyzed for functional comparison. The current drugs targeting ABL1 were statistically analyzed using DRUGSURV and DGIdb database. We found ABL1 is overexpressed in HCC and its higher expression reduces survival probability. Genetic changes of ABL1 are not frequent. We screened out 25 differentially expressed genes correlated with ABL1. The top functions of ABL1 are biological regulation, metabolic process, protein-containing, and protein binding. KEGG pathways showed that ABL1 and correlated with ABL1 significantly genes markedly enriched in the ErbB signaling pathway, and pathways in cancer. We counted the existing drugs targeting ABL1, which indicates that inhibiting ABL1 expression may improve the survival probability of HCC. In conclusion, ABL1 plays a crucial role in the development and progression of this cancerization and is a potential drug target.

PMID:35834027 | DOI:10.1007/s12032-022-01730-y