Tag: nevin manimala

JAMA Health Forum. 2024 Aug 2;5(8):e242446. doi: 10.1001/jamahealthforum.2024.2446.

ABSTRACT

IMPORTANCE: In Medicare Advantage (MA), step therapy for physician-administered drugs is an approach to lowering drug spending. The impact of step therapy in MA on prescribing behavior and the magnitude of any changes has not been analyzed.

OBJECTIVE: To evaluate the impact of step therapy on macular degeneration drug prescribing patterns for 3 large MA insurers.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective encounter-based analysis using 20% nationally representative MA outpatient and carrier encounter records for 2017 to 2019. Participants were MA beneficiaries who were 65 years or older and had received a macular degeneration drug administration. Macular degeneration drug administrations for beneficiaries of MA Aetna, Humana, and UnitedHealthcare (UHC) insurers were assessed. Humana implemented macular degeneration step therapy in 2019, setting bevacizumab as the plan-preferred drug, and aflibercept and ranibizumab as the plan-nonpreferred drugs. Aetna and UHC, which did not implement macular degeneration step therapy, served as the control group. Data analyses were performed from May 2024 to December 2024.

EXPOSURES: A macular degeneration drug administration subject to a step therapy policy.

MAIN OUTCOME AND MEASURES: A binary indicator of whether the drug administered was bevacizumab. Linear probability models and a difference-in-differences framework were used to quantify changes in prescribing patterns before and after the introduction of step therapy for MA insurers that did and did not implement step therapy. To empirically measure the impact of step therapy, the first administration of a treatment episode was assessed, followed by switching patterns.

RESULTS: A total of 18 331 MA beneficiaries, 21 683 treatment episodes, and 171 985 drug administrations were included across the control and treatment groups. The difference-in-differences regressions found a 7.8% (95% CI, 4.9%-10.7%; P < .001) greater probability of being prescribed bevacizumab for the first administration due to step therapy. The predicted probabilities of preferred-drug administration in the treatment group increased from 0.61 to 0.70 between the periods before and after step therapy implementation for the first administration. Step therapy was not significantly associated with an increased rate of medication switching (hazard ratio, 0.86; 95% CI, 0.71-1.06; P = .15).

CONCLUSIONS AND RELEVANCE: The findings of this retrospective encounter-based analysis indicate that step therapy is associated with a greater probability of prescribing the plan-preferred drug for the first administration. The analysis failed to find a statistically significant greater rate of medication switching within a treatment episode. Step therapy changed macular degeneration prescribing patterns, but step therapy alone did not transition all administrations to the plan-preferred drug.

PMID:39120894 | DOI:10.1001/jamahealthforum.2024.2446

Rheumatology (Oxford). 2024 Aug 9:keae383. doi: 10.1093/rheumatology/keae383. Online ahead of print.

ABSTRACT

BACKGROUND: The presence of autoantibodies against citrullinated proteins (ACPA) significantly increases the risk of developing rheumatoid arthritis (RA). Dysregulation of lymphocyte subpopulations was previously described in RA.

OBJECTIVES: To propose the predictive model for progression to clinical arthritis based on peripheral lymphocyte subsets and ACPA in individuals who are at risk of RA.

METHODS: Our study included 207 at-risk individuals defined by the presence of arthralgias and either additional ACPA positivity or meeting the EULAR definition for clinically suspect arthralgia. For the construction of predictive models, 153 individuals with symptom duration ≥12 months who have not yet progressed to arthritis were included. The lymphocyte subsets were evaluated using flow cytometry and anti-CCP using ELISA.

RESULTS: Out of all individuals with arthralgia, 41 progressed to arthritis. A logistic regression model with baseline peripheral blood lymphocyte subpopulations and ACPA as predictors was constructed. The resulting predictive model showed that high anti-CCP IgG, higher percentage of CD4+ T cells, and lower percentage of T and NK cells increased the probability of arthritis development. Moreover, the proposed classification decision tree showed, that individuals having both high anti-CCP IgG and low NK cells have the highest risk of developing arthritis.

CONCLUSIONS: We propose a predictive model based on baseline levels of lymphocyte subpopulations and ACPA to identify individuals with arthralgia with the highest risk of progression to clinical arthritis. The final model includes T cells and NK cells, which are involved in the pathogenesis of RA. This preliminary model requires further validation in larger at-risk cohorts.

PMID:39120892 | DOI:10.1093/rheumatology/keae383

Alzheimers Dement. 2023 Dec;19 Suppl 24:e082642. doi: 10.1002/alz.082642.

ABSTRACT

BACKGROUND: Varoglutamstat (PQ912) is an oral, small molecule inhibitor of glutaminyl cyclase, preventing the formation of neurotoxic N3pE amyloid. A Phase 2a study (NCT02389413, Scheltens et al., 2018) reported encouraging first evidence of varoglutamstat’s disease-modifying activity, most importantly with statistically significant changes from baseline in working memory after only 12 weeks of treatment.

METHOD: VIVIAD (NCT04498650, Vijverberg et al., 2021) is an informed multicenter, randomized, placebo-controlled, double-blind, parallel group dose-finding Phase 2b study in 250 patients with Mild Cognitive Impairment (MCI) and early Alzheimer´s disease (AD). Treatment duration varies between 48 and 96 weeks depending on the time of inclusion, with participants receiving 300mg or 600mg varoglutamstat, or placebo, twice-daily (BID). The participants’ disease status at time of inclusion was confirmed by Abeta_1-42 and phospho-tau CSF biomarker profiles, various cognition tests including MMSE, DSST/WAIS-IV Coding test (WAIS-IV), and A-IADL-Q. Primary outcome is a composite score of the cognitive domains attention and working memory using the Cogstate Neuropsychological Test Battery (Cogstate NTB).

RESULT: Enrollment has been completed, with a total of N = 259 patients randomized. The 300mg BID varoglutamstat arm was switched to 600mg BID based on positive independent Data Safety Monitoring Board review in June 2022. As of April 14, 2023, 23 patients had completed 96 weeks of treatment. The study will continue until the last patient has completed 48 weeks of treatment with the corresponding follow-up visit. While most AD trials focus on cognitive tests assessing memory deficits rather than working memory and attention, VIVIAD uses WAIS-IV to select patients with rescuable cognitive deficits in the target domains. In contrast to MMSE, WAIS-IV performance shows a reasonably good correlation with the primary outcome measures. Comparing baseline data of male and female participants showed no significant gender differences except for Abeta_1-42 levels.

CONCLUSION: The use of MMSE and DSST/WAIS-IV together with CSF biomarkers is a valuable tool in identifying and recruiting patients with MCI or mild AD. The strategy of recruiting individuals with evidence of baseline deficits on the WAIS-IV Coding test has successfully enriched the study cohort with respect to deficits in attention and working memory, enabling reliable assessment of potential cognitive improvement after treatment.

PMID:39120888 | DOI:10.1002/alz.082642

J Robot Surg. 2024 Aug 9;18(1):316. doi: 10.1007/s11701-024-02064-9.

ABSTRACT

Robotic pyelolithotomy continues to gain attention as an alternative to percutaneous nephrolithotomy (PCNL) for managing complex renal stones. We performed a single-arm meta-analysis and systematically searched the English-language literature published in PubMed, Web of Science, Scopus, and Google Scholar databases up to June 2024. The risk of non-randomized bias was assessed using ROBINS-I, and the quality of the literature was assessed using MINORS (Methodological Index for Non-Randomized Studies). Merger parameters were calculated using Stata16/SE under a random-effects model. Five non-comparative single-arm studies were included in the meta-analysis. Results showed that the operative time for robotic pyelolithotomy was 168.10 min (95% CI 133.63, 202.56). The hospital stay was 2.63 days (95% CI 0.96, 4.29), and blood loss was 44.13 ml (95% CI 19.76, 68.51). The stone clearance rate was 87% (95% CI 79-93%). The incidence of minor postoperative complications (Clavien grade I-II) was 23.7% (95% CI 13.4-35.8%), and the incidence of major complications (Clavien grade ≥ III) was 7% (95% CI 0.3-20.7%).The safety and efficacy of robotic pyelolithotomy in treating complex renal stones are acceptable, but future large prospective cohort studies are needed to validate the treatment.

PMID:39120845 | DOI:10.1007/s11701-024-02064-9

J Patient Rep Outcomes. 2024 Aug 9;8(1):88. doi: 10.1186/s41687-024-00774-0.

ABSTRACT

PURPOSE: Accurate assessment of chronic pain and functional disability in children and adolescents is imperative for guiding pain management interventions. Parents have multifaceted roles in their child’s pain experience and frequently provide parent-proxy reports of pain-related functioning. However, cross-informant variance is often observed with limited understanding of contributing factors. This study aims to examine the degree of alignment between child and parent-proxy reports for Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference domain among children with chronic pain and to identify factors associated with improved child-parent agreement.

METHODS: This study includes a sample of 127 youth (66.1% female) with mixed etiology chronic pain, ranging in age from 8 to 17 (M = 12.24; SD = 1.598), and their parent. Data was collected at an interdisciplinary pediatric pain clinic and online peer support groups. Measures of demographic, pain intensity, and functioning were collected.

RESULTS: Means of parent-proxy reports were significantly lower than child self-reports on the PROMIS (p < 0.05). A statistically significant association between child’s pain intensity (β = 0.953, P < 0.05) and the difference between child self-reported and parent-proxy reported PROMIS functional interference scores was found.

CONCLUSION: Parents underestimated pain-related functional disability relative to children’s self-reports. The difference between the paired child self-report and parent-proxy report of functional disability was significantly associated with greater child self-reported pain intensity. Although parent-proxy reports in pediatric chronic pain is often used in research and practice, findings underscore the importance of incorporating child and adolescent self-report, when possible, to comprehensively capture the child’s pain experience and best inform clinical interventions.

PMID:39120819 | DOI:10.1186/s41687-024-00774-0

Parasitol Res. 2024 Aug 9;123(8):297. doi: 10.1007/s00436-024-08317-8.

ABSTRACT

The effects of co-infections with SARS-CoV-2 and parasitic diseases have been little investigated in terms of immune response, disease dynamics, and clinical outcomes. This study aimed to explore the impact of co-infection with Opisthorchis viverrini and SARS-CoV-2 on the immune response concerning clinical symptoms and the severity of pulmonary abnormalities. A cross-sectional study was conducted, including healthy participants as controls, participants with opisthorchiasis, SARS-CoV-2 infection, and a co-infection group with both diseases. Characteristics of SARS-CoV-2 infection were assessed based on clinical parameters and severity of pulmonary abnormalities, whereas opisthorchiasis burden was evaluated by eggs-per-gram (EPG) counts. Immune responses were assessed by measuring levels of interferon-γ (IFN-γ), SARS-CoV-2 anti-spike receptor binding domain (RBD) IgG, and neutralizing antibody against SARS-CoV-2. In the co-infected group, clinical parameters and hospitalization rates were lower than in the SARS-CoV-2 group. Pulmonary abnormalities, such as bronchial fibrosis, were commonly observed in the SARS-CoV-2 group, leading to hospitalization in some cases. Participants with opisthorchiasis had higher IFN-γ levels than healthy individuals. IFN-γ levels were significantly lower in the co-infection group compared with the SARS-CoV-2 group (P = 0.002). There was a significant (P = 0.044) positive correlation between RBD-specific IgG and percent neutralization levels in the SARS-CoV-2 group. Levels of both were somewhat lower (not statistically significant) in the co-infection group. A negative correlation was observed between opisthorchiasis burden (EPG counts) and IFN-γ and RBD-specific IgG levels in the co-infected group. Following vaccination, the increase in IgG levels against the RBD protein was significantly lower in the co-infected group than in the SARS-CoV-2 group. These results suggest that O. viverrini infection suppresses immune responses and may lead to a reduction in severity in cases of SARS-CoV-2 co-infection.

PMID:39120805 | DOI:10.1007/s00436-024-08317-8

Eur Radiol. 2024 Aug 9. doi: 10.1007/s00330-024-11011-z. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate grayscale US combined with contrast-enhanced ultrasound (CEUS) in the preoperative differentiation between benign and malignant ovarian masses in a pediatric population.

MATERIALS AND METHODS: This retrospective study enrolled patients who underwent grayscale US and CEUS before surgery because of ovarian masses between July 2018 and September 2023, with available histopathologic or follow-up results. Two senior radiologists summarized the grayscale US and CEUS characteristics of all ovarian masses, including percentage of solidity, ascites, vascularity, and enhanced vessel morphology. These characteristics were then independently reviewed by radiologists with different experience to assess interobserver agreement. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC), while interobserver agreement was evaluated by intraclass correlation coefficient (ICC).

RESULTS: A total of 26 children (median age: 10.1 [7.5, 11.7] years; age range: 0-14 years; benign: 15 patients) were included. The main characteristics of malignant ovarian tumors were abundant blood flow and twisted blood vessels within the mass, enhanced portion of the mass over 50 percent (all p < 0.001). The grayscale US combined with CEUS showed better diagnostic performance than the grayscale US alone (AUC = 0.99 [95% CI: 0.95, 1.00] vs AUC = 0.70 [95% CI: 0.50, 0.90] p < 0.001). A statistically significant AUC before and after CEUS was also shown between two junior radiologists (0.75 vs 0.92 and 0.69 vs 0.86, respectively, both p < 0.05). ICC of CEUS was better than that of grayscale US among radiologists.

CONCLUSION: The combination of grayscale US and CEUS might improve the diagnostic accuracy in differentiating benign and malignant pediatric ovarian masses.

CLINICAL RELEVANCE STATEMENT: Grayscale ultrasound combined with contrast-enhanced ultrasound can improve the diagnostic performance in the preoperative differentiation of benign and malignant ovarian lesions in a pediatric population.

KEY POINTS: Correctly distinguishing benign from malignant ovarian masses in pediatric patients is critical for determining treatments. Grayscale combined with contrast-enhanced ultrasound (CEUS) differentiated benign and malignant pediatric ovarian masses better than grayscale US alone. Junior radiologists’ diagnostic performances could be and were significantly improved with the application of CEUS.

PMID:39120792 | DOI:10.1007/s00330-024-11011-z

Community Ment Health J. 2024 Aug 9. doi: 10.1007/s10597-024-01331-1. Online ahead of print.

ABSTRACT

Virtual clinical services became the primary treatment modality in a large U.S. HMO psychiatry department during the COVID-19 pandemic. A mixed methods quality improvement project was developed to address psychosis, severe anxiety, and stressors unique to COVID-19 and sheltering in place. The purpose was to determine if a virtual 10-week pilot program combining psychoeducation, skills-based training, experiential exercises using third-wave CBT, and process questions would decrease symptoms and hospitalization rates and improve quality of life. Pre- and postmeasure scores on pandemic-related stress (the PRSF), perceived stress (PSS), and general patient health (PHQ-9) were gathered from five patients in the Department of Psychiatry at Kaiser Permanente in Oakland, California. Qualitative interviews explored patients’ perceptions of program benefits. Mean, median, and range on the pre- and postprogram assessments and paired samples t tests for means were calculated. Quantitative results were not statistically significant: p = 0.32 (Revised PRSF), p = 0.34 (PSS), p = 0.94 (PHQ-9). In interviews, most participants reported a decrease in pandemic-related stress. Half reported a decrease in general perceived stress. Half reported no change. Self-assessment reflected perceptions of benefits from this 10-week program, using words such as useful and important. The virtual program helped relieve pandemic-related stress and improved overall quality of life. The results show promise for expanding the program to other hospitals providing services for this diagnostic population.

PMID:39120778 | DOI:10.1007/s10597-024-01331-1

Discov Oncol. 2024 Aug 9;15(1):341. doi: 10.1007/s12672-024-01218-3.

ABSTRACT

Lymphocytes are important for protective immunity against infections and cancers, and dysregulation of the immune system may lead to systemic lupus erythematosus (SLE). Metabolic adaptation regulates the fate of lymphocytes. The immune microenvironment is vital role in both SLE and gynecological malignancies. The disruption of the immune microenvironment in SLE is one of the key factors leading to disease occurrence. Overactive autoimmunity indices the body to attack its own tissues, leading to the formation of immune complexes that further trigger tissue damage and inflammation. This imbalance in the immune microenvironment affects the progression of SLE and may also indirectly affect the occurrence of gynecological cancers. For gynecological cancers, immune cells, cytokines, and chemokines in the tumor microenvironment jointly comprise a complex network, and their interactions determine cancer growth, invasion, and metastasis. Mendelian randomization analysis revealed that SLE does not have a statistically significant causal effect on the risk of common cancers of the female reproductive system such as cervical, endometrial, and ovarian cancers in the European population. However, the odds ratio < 1 in the inverse variance weighted results suggest the potential of SLE as a protective factor for endometrial cancer.

PMID:39120776 | DOI:10.1007/s12672-024-01218-3

Cancer Med. 2024 Aug;13(15):e7399. doi: 10.1002/cam4.7399.

ABSTRACT

INTRODUCTION: The impact of chemoimmunotherapy (CIT) on immunoglobulin (Ig) quantities in patients with chronic lymphocytic leukemia (CLL) has not been extensively studied.

METHODS: We analyzed Ig levels in 45 stable patients with indolent CLL (without indication for treatment) and 87 patients with progressive disease before first-line treatment. Fifty-five patients were evaluated again after the treatment with CIT.

RESULTS: We observed significantly lower levels of all Ig classes and subclasses in patients with progressive disease compared to patients with indolent disease. After treatment, median IgA increased from 0.59 g/L to 0.74 g/L (p = 0.0031). In stable patients, lower IgA2 was associated with shorter time to first treatment, although it did not reach statistical significance (p = 0.056). Shorter overall survival was observed in patients with progressive disease and lower IgG2 (p = 0.043). Surprisingly, among the patients with progressive CLL, unmutated IGHV genes were associated with higher levels of IgG, IgG1 and IgM, while TP53 mutation and/or 17p deletion were associated with higher levels of IgA and IgA1.

CONCLUSIONS: CIT may lead to increase in IgA levels. Hypogammaglobulinemia is more common in patients with progressive CLL and unmutated IGHV or TP53 dysfunction.

PMID:39119792 | DOI:10.1002/cam4.7399