Tag: nevin manimala

Inflamm Bowel Dis. 2023 Jun 26:izad115. doi: 10.1093/ibd/izad115. Online ahead of print.

ABSTRACT

BACKGROUND: Antitumor necrosis factor (anti-TNF) inhibitors are first-line treatment among patients with ulcerative colitis (UC). With time, patients tend to lose response or become intolerant, necessitating switching to small cell biologics such as tofacitinib or vedolizumab. In this real-world study of a large, geographically diverse US population of TNF-experienced patients with UC, we evaluated the effectiveness and safety of newly initiating treatment with tofacitinib vs vedolizumab.

METHODS: We conducted a cohort study using secondary data from a large US insurer (Anthem, Inc.). Our cohort included patients with UC newly initiating treatment with tofacitinib or vedolizumab. Patients were required to have evidence of treatment with anti-TNF inhibitors in the 6 months prior to cohort entry. The primary outcome was treatment persistence >52 weeks. Additionally, we evaluated the following secondary outcomes as additional measures of effectiveness and safety: (1) all-cause hospitalization; (2) total abdominal colectomy; (3) hospitalization for infection; (4) hospitalization for malignancy; (5) hospitalization for cardiac events; and (6) hospitalization for thromboembolic events. We used fine stratification by propensity scores to control for confounding by demographics, clinical factors, and treatment history at baseline.

RESULTS: Our primary cohort included 168 new users of tofacitinib and 568 new users of vedolizumab. Tofacitinib was associated with lower treatment persistence (adjusted risked ratio, 0.77; 95% CI, 0.60 -0.99). Differences in secondary measures of effectiveness or safety between tofacitinib initiators vs vedolizumab initiators were not statistically significant (all-cause hospitalization, adjusted hazard ratio, 1.23; 95% CI, 0.83-1.84; total abdominal colectomy, adjusted HR, 1.79; 95% CI, 0.93-3.44;and hospitalization for any infection, adjusted HR, 1.94; 95% CI, 0.83-4.52).

DISCUSSION: Ulcerative colitis patients with prior anti-TNF experience initiating tofacitinib demonstrated lower treatment persistence compared with those initiating vedolizumab. This finding is in contrast to other recent studies suggesting superior effectiveness of tofacitinib. Ultimately, head-to-head randomized, controlled trials that focus on directly measured end points may be needed to best inform clinical practice.

PMID:37358904 | DOI:10.1093/ibd/izad115

J Med Internet Res. 2023 Jun 26;25:e46771. doi: 10.2196/46771.

ABSTRACT

BACKGROUND: Suicide is a global public health problem. Digital interventions are considered a low-threshold treatment option for people with suicidal ideation or behaviors. Internet-based cognitive behavioral therapy (iCBT) targeting suicidal ideation has demonstrated effectiveness in reducing suicidal ideation. However, suicidal ideation often is related to additional mental health problems, which should be addressed for optimal care. Yet, the effects of iCBT on related symptoms, such as depression, anxiety, and hopelessness, remain unclear.

OBJECTIVE: We aimed to analyze whether digital interventions targeting suicidal ideation had an effect on related mental health symptoms (depression, anxiety, and hopelessness).

METHODS: We systematically searched CENTRAL, PsycInfo, Embase, and PubMed for randomized controlled trials that investigated guided or unguided iCBT for suicidal ideation or behaviors. Participants reporting baseline suicidal ideation were eligible. Individual participant data (IPD) were collected from eligible trials. We conducted a 1-stage IPD meta-analysis on the effects on depression, anxiety, and hopelessness-analyzed as 2 indices: symptom severity and treatment response.

RESULTS: We included IPD from 8 out of 9 eligible trials comprising 1980 participants with suicidal ideation. iCBT was associated with significant reductions in depression severity (b=-0.17; 95% CI -0.25 to -0.09; P<.001) and higher treatment response (ie, 50% reduction of depressive symptoms; b=0.36; 95% CI 0.12-0.60; P=.008) after treatment. We did not find significant effects on anxiety and hopelessness.

CONCLUSIONS: iCBT for people with suicidal ideation revealed significant effects on depression outcomes but only minor or no effects on anxiety and hopelessness. Therefore, individuals with comorbid symptoms of anxiety or hopelessness may require additional treatment components to optimize care. Studies that monitor symptoms with higher temporal resolution and consider a broader spectrum of factors influencing suicidal ideation are needed to understand the complex interaction of suicidality and related mental health symptoms.

PMID:37358893 | DOI:10.2196/46771

JMIR Res Protoc. 2023 Jun 26;12:e46816. doi: 10.2196/46816.

ABSTRACT

BACKGROUND: Allergic diseases affect around 40% of the pediatric population worldwide. The coexistence of asthma, allergic rhinitis, eczema, and food allergy renders allergy treatment and prevention challenging. Infant feeding strategies recommend avoiding allergenic foods to prevent allergy development and anaphylaxis. However, recent evidence suggests that early consumption of food allergens during weaning in infants aged 4-6 months could result in food tolerance, thus reducing the risk of developing allergies.

OBJECTIVE: The aim of this study is to systematically review and carry out a meta-analysis of evidence on the outcome of early food introduction for preventing childhood allergic diseases.

METHODS: We will conduct a systematic review of interventions through a comprehensive search of various databases including PubMed, Embase, Scopus, CENTRAL, PsycINFO, CINAHL, and Google Scholar to identify potential studies. The search will be performed for any eligible articles from the earliest published articles up to the latest available studies in 2023. We will include randomized controlled trials (RCTs), cluster RCTs, non-RCTs, and other observational studies that assess the effect of early food introduction to prevent childhood allergic diseases.

RESULTS: Primary outcomes will include measures related to the effect of childhood allergic diseases (ie, asthma, allergic rhinitis, eczema, and food allergy). PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines will be followed for study selection. All data will be extracted using a standardized data extraction form and the quality of the studies will be assessed using the Cochrane Risk of Bias tool. A summary of findings table will be generated for the following outcomes: (1) total number of allergic diseases, (2) rate of sensitization, (3) total number of adverse events, (4) improvement of health-related quality of life, and (5) all-cause mortality. Descriptive and meta-analyses will be performed using a random-effects model in Review Manager (Cochrane). Heterogeneity among selected studies will be assessed using the I² statistic and explored through meta-regression and subgroup analyses. Data collection is expected to start in June 2023.

CONCLUSIONS: The results acquired from this study will contribute to the existing literature and harmonize recommendations for infant feeding with regard to the prevention of childhood allergic diseases.

TRIAL REGISTRATION: PROSPERO CRD42021256776; https://tinyurl.com/4j272y8a.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46816.

PMID:37358892 | DOI:10.2196/46816

J Med Internet Res. 2023 Jun 26;25:e43633. doi: 10.2196/43633.

ABSTRACT

BACKGROUND: Engagement is key to interventions that achieve successful behavior change and improvements in health. There is limited literature on the application of predictive machine learning (ML) models to data from commercially available weight loss programs to predict disengagement. Such data could help participants achieve their goals.

OBJECTIVE: This study aimed to use explainable ML to predict the risk of member disengagement week by week over 12 weeks on a commercially available web-based weight loss program.

METHODS: Data were available from 59,686 adults who participated in the weight loss program between October 2014 and September 2019. Data included year of birth, sex, height, weight, motivation to join the program, use statistics (eg, weight entries, entries into the food diary, views of the menu, and program content), program type, and weight loss. Random forest, extreme gradient boosting, and logistic regression with L1 regularization models were developed and validated using a 10-fold cross-validation approach. In addition, temporal validation was performed on a test cohort of 16,947 members who participated in the program between April 2018 and September 2019, and the remaining data were used for model development. Shapley values were used to identify globally relevant features and explain individual predictions.

RESULTS: The average age of the participants was 49.60 (SD 12.54) years, the average starting BMI was 32.43 (SD 6.19), and 81.46% (39,594/48,604) of the participants were female. The class distributions (active and inactive members) changed from 39,369 and 9235 in week 2 to 31,602 and 17,002 in week 12, respectively. With 10-fold-cross-validation, extreme gradient boosting models had the best predictive performance, which ranged from 0.85 (95% CI 0.84-0.85) to 0.93 (95% CI 0.93-0.93) for area under the receiver operating characteristic curve and from 0.57 (95% CI 0.56-0.58) to 0.95 (95% CI 0.95-0.96) for area under the precision-recall curve (across 12 weeks of the program). They also presented a good calibration. Results obtained with temporal validation ranged from 0.51 to 0.95 for area under a precision-recall curve and 0.84 to 0.93 for area under the receiver operating characteristic curve across the 12 weeks. There was a considerable improvement in area under a precision-recall curve of 20% in week 3 of the program. On the basis of the computed Shapley values, the most important features for predicting disengagement in the following week were those related to the total activity on the platform and entering a weight in the previous weeks.

CONCLUSIONS: This study showed the potential of applying ML predictive algorithms to help predict and understand participants’ disengagement with a web-based weight loss program. Given the association between engagement and health outcomes, these findings can prove valuable in providing better support to individuals to enhance their engagement and potentially achieve greater weight loss.

PMID:37358890 | DOI:10.2196/43633

Oncologist. 2023 Jun 26:oyad170. doi: 10.1093/oncolo/oyad170. Online ahead of print.

ABSTRACT

BACKGROUND: This retrospective, real-world study evaluated the prevalence of brain metastases, clinicodemographic characteristics, systemic treatments, and factors associated with overall survival among patients with advanced non-small cell lung cancer (aNSCLC) in the US. We also described the genomic characterization of 180 brain metastatic specimens and frequency of clinically actionable genes.

MATERIALS AND METHODS: De-identified electronic health records-derived data of adult patients diagnosed with aNSCLC between 2011 and 2017 were analyzed from a US-nationwide clinicogenomic database.

RESULTS: Of 3257 adult patients with aNSCLC included in the study, approximately 31% (n = 1018) had brain metastases. Of these 1018 patients, 71% (n = 726) were diagnosed with brain metastases at initial NSCLC diagnosis; 57% (n = 583) of patients with brain metastases received systemic treatment. Platinum-based chemotherapy combinations were the most common first-line therapy; single-agent chemotherapies, epidermal growth factor receptor tyrosine kinase inhibitors, and platinum-based chemotherapy combinations were used in second line. Patients with brain metastases had a 1.56 times greater risk of death versus those with no brain metastases. In the brain metastatic specimens (n = 180), a high frequency of genomic alterations in the p53, MAPK, PI3K, mTOR, and cell-cycle associated pathways was observed.

CONCLUSION: The frequency of brain metastases at initial clinical presentation and associated poor prognosis for patients in this cohort underscores the importance of early screening for brain metastasis in NSCLC. Genomic alterations frequently identified in this study emphasize the continued need for genomic research and investigation of targeted therapies in patients with brain metastases.

PMID:37358877 | DOI:10.1093/oncolo/oyad170

Appl Immunohistochem Mol Morphol. 2023 Jun 26. doi: 10.1097/PAI.0000000000001139. Online ahead of print.

ABSTRACT

Breast cancer is a heterogenous disease at the molecular level thus, it can be hypothesized that different molecular subtypes differ in their tumor microenvironment (TME) also. Understanding the TME heterogeneity may provide new prognostic biomarkers and new targets for cancer therapy. For deciphering heterogeneity in the TME, immunohistochemistry for immune markers (CD3, CD4, CD8, CD68, CD163, and programmed death-ligand 1), Cancer-associated fibroblast markers [anti-fibroblast activating protein α (FAP-α), platelet-derived growth factor receptor α (PDGFR-α), S100A4, Neuron-glial antigen 2, and Caveolin-1], and angiogenesis (CD31) was performed on tissue microarrays of different molecular subtypes of breast cancer. High CD3+ T cells were noted in the Luminal B subtype (P=0.002) of which the majority were CD8+ cytotoxic T cells. Programmed death-ligand 1 expression in immune cells was highest in the human epidermal growth factor receptor 2 (Her-2)-positive and Luminal B subtypes compared with the triple-negative breast cancer (TNBC) subtype (P=0.003). Her-2 subtype is rich in M2 tumor-associated macrophages (P=0.000) compared with TNBC and Luminal B subtypes. M2 immune microenvironment correlated with high tumor grade and high Ki-67. Her-2 and TNBC subtypes are rich in extracellular matrix remodeling (FAP-α, P=0.003), angiogenesis-promoting (PDGFR-α; P=0.000) and invasion markers (Neuron-glial antigen 2, P=0.000; S100A4, P=0.07) compared with Luminal subtypes. Mean Microvessel density showed an increasing trend: Luminal A>Luminal B>Her-2 positive>TNBC; however, this difference was not statistically significant. The cancer-associated fibroblasts (FAP-α, PDGFR-α, and Neuron-glial antigen 2) showed a positive correlation with lymph node metastasis in specific subtypes. Immune cells, tumor-associated macrophage, and cancer-associated fibroblast-related stromal markers showed higher expression in Luminal B, Her-2 positive, and TNBC respectively. This differential expression of different components of TME indicates heterogeneity of the TME across molecular subtypes of breast cancer.

PMID:37358863 | DOI:10.1097/PAI.0000000000001139

JAMA Netw Open. 2023 Jun 1;6(6):e2320035. doi: 10.1001/jamanetworkopen.2023.20035.

ABSTRACT

IMPORTANCE: While the incidence of early-onset metastatic colorectal cancer (mCRC) has been increasing, studies on the age-related disparity in this group of patients are limited.

OBJECTIVE: To evaluate the association of age with treatment-related adverse events and survival in patients with mCRC and explore the potential underlying factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 1959 individuals. Individual data on 1223 patients with mCRC who received first-line fluorouracil and oxaliplatin therapy in 3 clinical trials, and clinical and genomic data of 736 patients with mCRC from Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort. All statistical analyses were conducted from October 1, 2021, through November 12, 2022.

EXPOSURES: Metastatic colorectal cancer.

MAIN OUTCOMES AND MEASURES: Survival outcomes and treatment-related adverse events were compared among patients in 3 age groups: younger than 50 (early onset), 50 to 65, and older than 65 years.

RESULTS: In the total population of 1959 individuals, 1145 (58.4%) were men. Among 1223 patients from previous clinical trials, 179 (14.6%) in the younger than 50 years group, 582 (47.6%) in the 50 to 65 years group, and 462 (37.8%) in the older than 65 years group had similar baseline characteristics except for sex and race. The younger than 50 years group had significantly shorter progression-free survival (PFS) (hazard ratio [HR], 1.46; 95% CI, 1.22-1.76; P < .001) and overall survival (OS) (HR, 1.48; 95% CI, 1.19-1.84; P < .001) compared with the 50 to 65 years group after adjustment for sex, race, and performance status. Significantly shorter OS in the younger than 50 years group was confirmed in the Moffitt cohort. The younger than 50 years group had a significantly higher incidence of nausea and vomiting (69.3% vs 57.6% [50-65 years] vs 60.4% [>65 years]; P = .02), severe abdominal pain (8.4% vs 3.4% vs 3.5%; P = .02), severe anemia (6.1% vs 1.0% vs 1.5%; P < .001), and severe rash (2.8% vs 1.2% vs 0.4% P = .047). The younger than 50 years group also had earlier onset of nausea and vomiting (1.0 vs 2.1 vs 2.6 weeks; P = .01), mucositis (3.6 vs 5.1 vs 5.7 weeks; P = .05), and neutropenia (8.0 vs 9.4 vs 8.4 weeks; P = .04), and shorter duration of mucositis (0.6 vs 0.9 vs 1.0 weeks; P = .006). In the younger than 50 years group, severe abdominal pain and severe liver toxic effects were associated with shorter survival. The Moffitt genomic data showed that the younger than 50 years group had a higher prevalence of CTNNB1 mutation (6.6% vs 3.1% vs 2.3%; P = .047), ERBB2 amplification (5.1% vs 0.6% vs 2.3%; P = .005), and CREBBP mutation (3.1% vs 0.9% vs 0.5%; P = .05), but lower prevalence of BRAF mutation (7.7% vs 8.5% vs 16.7%; P = .002).

CONCLUSIONS AND RELEVANCE: In this cohort study of 1959 patients, those with early-onset mCRC showed worse survival outcomes and unique adverse event patterns, which could be partially attributed to distinct genomic profiles. These findings may inform individualized management approaches in patients with early-onset mCRC.

PMID:37358854 | DOI:10.1001/jamanetworkopen.2023.20035

Appl Immunohistochem Mol Morphol. 2023 Jun 27. doi: 10.1097/PAI.0000000000001140. Online ahead of print.

ABSTRACT

PD-L1 IHC 22C3 pharmDx is an FDA-approved companion test to select patients for anti-PD-L1 immunotherapy. In head and neck squamous cell carcinoma PD-L1 expression is determined using a Combined Positive Score (CPS), which evaluates expression in tumor cells and tumor-associated leukocytes. We hypothesized that in nodal metastasis, the CPS should be higher given their inherent higher proportion of leukocytes. A significant difference in CPS between sites would mean that the tissue chosen for PD-L1 testing would impact patient eligibility for therapy. Currently, guidelines about which tissue should be tested do not exist. PD-L1 22C3 IHC was performed in the primary and nodal metastases of 35 head and neck squamous cell carcinoma, and a CPS was generated by 3 pathologists. Mean CPS was higher at the primary than the nodal metastasis: 47.2 versus 42.2; however, the difference was not statistically significant: P=0.259. By therapeutic groups: negative (CPS <1), low (CPS 1-19) and high (CPS≥20), low-expression was more common in the primary: 40 vs. 26%, and high-expression in the nodal metastasis: 74 vs. 60% but this difference was not statistically significant: P=0.180. Stratified by positive versus negative (CPS <1 vs. ≥1), there were no differences between sites. Interobserver agreement for CPS among the 3 raters was slight for both sites: ƙ=0.117 and 0.025, fair if stratified by therapeutic group: ƙ=0.371 and 0.318, and near perfect if stratified as negative versus positive: ƙ=0.652 and 1. There were no statistically significant differences in CPS between primary and nodal metastases independent of how the CPS was stratified.

PMID:37358840 | DOI:10.1097/PAI.0000000000001140

Phys Eng Sci Med. 2023 Jun 26. doi: 10.1007/s13246-023-01287-8. Online ahead of print.

ABSTRACT

High-density catheters combined with Orientation Independent Sensing (OIS) methods have emerged as a groundbreaking technology for cardiac substrate characterisation. In this study, we aim to assess the arrangements and constraints to reliably estimate the so-called omnipolar electrogram (oEGM). Performance was evaluated using an experimental animal model. Thirty-eight recordings from nine retrospective experiments on isolated perfused rabbit hearts with an epicardial HD multielectrode were used. We estimated oEGMs according to the classic triangular clique (4 possible orientations) and a novel cross-orientation clique arrangement. Furthermore, we tested the effects of interelectrode spacing from 1 to 4 mm. Performance was evaluated by means of several parameters that measured amplitude rejection ratios, electric field loop area, activation pulse width and morphology distortion. Most reliable oEGM estimations were obtained with cross-configurations and interelectrode spacings [Formula: see text] mm. Estimations from triangular cliques resulted in wider electric field loops and unreliable detection of the direction of the propagation wavefront. Moreover, increasing interelectrode distance resulted in increased pulse width and morphology distortion. The results prove that current oEGM estimation techniques are insufficiently accurate. This study opens a new standpoint for the design of new-generation HD catheters and mapping software.

PMID:37358782 | DOI:10.1007/s13246-023-01287-8

Matern Child Health J. 2023 Jun 26. doi: 10.1007/s10995-023-03704-6. Online ahead of print.

ABSTRACT

OBJECTIVES: Technology-based outreach offers promise for providing support to a broad population of postpartum mothers while keeping costs low. However, research on the efficacy of this approach is scarce. We conducted a pre-registered randomized pilot trial of the effects of a novel technology-based approach for supporting postpartum mothers – via text-based mentoring – from infant’s birth through 18 months.

METHODS: Mothers (n = 201) were recruited at West Penn Hospital in Pittsburgh, PA in the days immediately following delivery. Treatment mothers were matched with volunteer mentors who communicated with them entirely via text messages. Control mothers received monthly one-way texts on basic safety topics. Measures were collected via hospital records and mother surveys. We estimated treatment effects on mothers’ parenting stress, mental health, knowledge of child development, engagement in language and literacy activities, and child milestones at 4- and 18-months postpartum. We used a systematic coding approach and simple descriptive statistics to analyze the treatment mother-mentor texting transcripts.

RESULTS: We found no statistically significant impacts on targeted outcomes. However, impacts for some outcomes were meaningfully large (> 0.2 SDs). Analyses of texting transcripts showed that most mothers stayed engaged for the full 18-month study period and that mother-mentor pairs primarily discussed maternal wellbeing and child-focused topics.

CONCLUSIONS FOR PRACTICE: Postpartum mothers will engage with mentors in a text-based mentoring program around important maternal and child health topics. More research and development on technology-based supports for parents in the early childhood years is needed.

PMID:37358777 | DOI:10.1007/s10995-023-03704-6