Nevin Manimala

JMIR Res Protoc. 2023 Aug 31;12:e47717. doi: 10.2196/47717.

ABSTRACT

BACKGROUND: This co-design research method details the iterative process developed to identify health professional recommendations for the graphical user interface (GUI) of an artificial intelligence (AI)-enabled risk prediction tool. Driving the decision to include a co-design process is the belief that choices regarding the aesthetic and functionality of an intervention are best made by its intended users and that engaging these users in its design will promote the tool’s adoption and use.

OBJECTIVE: The aim of this research is to identify health professional design and uptake recommendations for the GUI of an AI-enabled predictive risk tool.

METHODS: We will hold 3 research phases, each consisting of 2 workshops with health professionals, between mid-2023 and mid-2024. A total of 6 health professionals will be sought per workshop, resulting in a total enrollment of 36 health professionals at the conclusion of the research. A total of 7 workshop activities have been scheduled across the 3 workshops; these include context of use, notifiers, format, AI survey-Likert, prototype, AI survey-written, and testing. The first 6 of these activities will be repeated in each workshop to enable the iterative development and refinement of GUI. The last activity (testing) will be performed in the final workshop to examine health professionals’ thoughts on the final GUI iteration. Qualitative and quantitative results data will be produced from tasks in each research activity. Qualitative data will be examined through inductive thematic analysis or deductive thematic analysis in accordance with the Nonadoption, Abandonment, and Challenges to the Scale-up, Spread, and Sustainability (NASSS) framework; visual data will be examined in accordance with “framework of interactivity;” and quantitative data will be examined using descriptive statistics.

RESULTS: Project registration with the Australia and New Zealand Clinical Trial Registry has been requested (#384098). Finalized design recommendations are expected in early to mid-2024, with a results manuscript to be submitted in mid-2024. This research method has human research ethics approval from the South Australian Department of Health and Wellbeing (#2022/HRE00131) as well as from the Human Research Ethics Committee of the University of South Australia (application ID#204143).

CONCLUSIONS: Understanding whether an intervention is needed in a particular situation is just the start; designing an intervention so that it is used within that situation is paramount. This co-design process engages end users to create a GUI that includes the aesthetic and functional details they need in a manner that aligns with their existing work practices. Indeed, interventions that fail to do this may be disliked, and at worst, they may be dangerous.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/47717.

PMID:37651166 | DOI:10.2196/47717

Cancer. 2023 Aug 31. doi: 10.1002/cncr.35007. Online ahead of print.

ABSTRACT

BACKGROUND: One in three patients with stage III colon cancer will experience tumor recurrence. It is uncertain whether physical activity during and after postoperative chemotherapy for stage III colon cancer improves overall survival after tumor recurrence.

METHODS: A prospective cohort study nested within a randomized multicenter trial of patients initially diagnosed with stage III colon cancer who experienced tumor recurrence (N = 399) was conducted. Postoperative physical activity before tumor recurrence was measured. Physical activity energy expenditure was quantified via metabolic equivalent task hours per week (MET-h/week). The primary end point was overall survival after tumor recurrence. Multivariable flexible parametric survival models estimated relative and absolute effects with two-sided hypothesis tests.

RESULTS: Compared with patients expending <3.0 MET-h/week of physical activity (comparable to <1.0 h/week of brisk walking), patients with ≥18.0 MET-h/week of physical activity (comparable to 6 h/week of brisk walking) had a 33% relative improvement in overall survival time after tumor recurrence (hazard ratio, 0.67; 95% CI, 0.42-0.96). The overall survival rate at 3 years after tumor recurrence was 61.3% (95% CI, 51.8%-69.2%) with <3.0 MET-h/week of physical activity and 72.2% (95% CI, 63.1%-79.6%) with ≥18 MET-h/week of physical activity (risk difference, 10.9 percentage points; 95% CI, 1.2-20.8 percentage points).

CONCLUSIONS: Higher postoperative physical activity is associated with improved overall survival after tumor recurrence in patients initially diagnosed with stage III colon cancer. These data may be relevant to patients who, despite optimal postoperative medical therapy, have a high risk of tumor recurrence.

PMID:37651160 | DOI:10.1002/cncr.35007

JAMA Otolaryngol Head Neck Surg. 2023 Aug 31. doi: 10.1001/jamaoto.2023.2420. Online ahead of print.

ABSTRACT

IMPORTANCE: The US Food and Drug Administration approved immune checkpoint inhibitors (immunotherapy) for select cases of head and neck squamous cell carcinoma (HNSCC) in 2016. However, it is unclear whether there are clinical or sociodemographic differences among patients receiving immunotherapy as part of their care. Given the known disparities in head and neck cancer care, we hypothesized that there are differences in receipt of immunotherapy among patients with HNSCC based on clinical and nonclinical characteristics.

OBJECTIVE: To characterize clinical and nonclinical factors associated with receipt of immunotherapy among older patients with HNSCC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients 65 years or older diagnosed with HNSCC (n = 4860) in a community oncology care setting. Electronic health records from Navigating Cancer were assessed from January 1, 2017, to April 30, 2022.

MAIN OUTCOMES AND MEASURES: Multivariable logistic regression was used to characterize clinical (tumor stage [localized vs advanced] and anatomical subsite [oropharyngeal vs nonoropharyngeal]) and nonclinical (age, smoking history, race and ethnicity, sex, and marital status) factors associated with receipt of immunotherapy.

RESULTS: In the study cohort of 4860 patients, 3593 (73.9%) were men; 4230 (87.0%) were White and 630 (13.0%) were of other races. A total of 552 patients (11.4%) had received immunotherapy. After adjusting for covariates, in the final model, White patients with HNSCC had 80% increased odds of receiving immunotherapy (adjusted odds ratio [AOR], 1.80 [95% CI, 1.30-2.48]) compared with patients of other races. There were no statistically significant differences in the odds of receiving immunotherapy based on age, sex, or smoking history. Patients with nonoropharyngeal disease were significantly more likely to receive immunotherapy than those with oropharyngeal cancer (AOR, 1.29 [95% CI, 1.05-1.59]), as were those with advanced compared with local disease (AOR, 2.39 [95% CI, 1.71-3.34]).

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that among older patients with HNSCC, White patients may be more likely to receive immunotherapy as part of their care. Equitable access to immunotherapy and other treatment options will reduce cancer-related health disparities and improve survival of patients with HNSCC.

PMID:37651149 | DOI:10.1001/jamaoto.2023.2420

JAMA Netw Open. 2023 Aug 1;6(8):e2330870. doi: 10.1001/jamanetworkopen.2023.30870.

ABSTRACT

IMPORTANCE: The association of hepatitis B virus (HBV) infection with reduced fecundability among reproductive-aged couples lacks large-population, in-depth study evidence.

OBJECTIVE: To investigate the association of HBV infection with time to pregnancy in couples planning pregnancy, and to explore whether this association varied by gravidity, health statuses, or lifestyles.

DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study of Chinese couples participating in the National Free Preconception Check-up Projects during 2015 to 2017. They were planning pregnancy and were followed-up every 3 months until getting pregnant, as confirmed by gynecologic ultrasonography, or were followed-up for 1 year. Data were analyzed between March 1, 2022, and September 30, 2022.

MAIN OUTCOMES AND MEASURES: The main outcome was time to pregnancy, assessed using fecundability hazard ratios (HRs). The Cox proportional hazards regression models were used to estimate the association of HBV infection with fecundability.

RESULTS: Among 2 419 848 couples (mean [SD] age, 27.87 [5.20] years for women and 29.58 [5.50] years for men), 126 728 women (5.24%) and 156 572 men (6.47%) were infected with HBV. Compared with the HBV-negative group, the fecundability of both women and men in the HBV-positive group decreased by 5% (HR, 0.95; 95% CI, 0.94-0.95). Compared with couples in which both partners were HBV negative, the fecundability of those in which both partners were HBV positive declined by 6% (HR, 0.94; 95% CI, 0.93-0.96) among all couples, by 3% (HR, 0.97; 95% CI, 0.95-0.99) among nulligravidas couples, and by 7% (HR, 0.93; 95% CI, 0.91-0.95) among multigravidas couples. Both the female-male and couple models suggested that the association of HBV infection with decreased fecundability was more pronounced in couples with multigravidas. The negative association was greater in people with overweight and obesity and was inconsistent in certain subgroups; in particular, it was more pronounced in women with reproductive tract infections, normal fasting plasma glucose, and no alcohol intake and in men with normal blood pressure.

CONCLUSIONS AND RELEVANCE: In this population-based cohort study, HBV infection was associated with decreased fecundability in a general reproductive-aged population, especially in couples with multigravidas. For women and men with certain health statuses and lifestyles, a comprehensive consideration of this association is recommended to provide personalized fertility guidance.

PMID:37651142 | DOI:10.1001/jamanetworkopen.2023.30870

JAMA Netw Open. 2023 Aug 1;6(8):e2331815. doi: 10.1001/jamanetworkopen.2023.31815.

ABSTRACT

IMPORTANCE: Birth weight percentiles (BWPs) are often dichotomized at the 10th percentile and show statistically significant association with later cognitive performance, for both preterm and term-born children. However, research testing nonlinear associations between BWPs and cognitive performance is scarce.

OBJECTIVE: To investigate culturally invariant, nonlinear associations of BWPs and gestational age with later cognitive performance.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, participants with valid neonatal and cognitive data were combined from 4 observational cohorts, including the Millennium Cohort Study, the National Longitudinal Survey of Youth 1979 Child and Young Adult cohort, Growing Up in Ireland, and the Longitudinal Study of Australian Children, with children born between 2000 and 2002, 1980 and 2010, 2007 and 2008, and 2003 and 2004, respectively. Neonatal data were parent reported before age 1 year. At approximately 5 years of age, multiple cognitive tests were performed. Follow-up at 5 years of age was the predominant focus. Data were analyzed July 17, 2023.

EXPOSURE: The parent-reported neonatal data were used to calculate BWPs according to the Fenton growth chart.

MAIN OUTCOME AND MEASURE: Scores for IQ were created from multiple measures of cognition, which were z standardized separately within each cohort.

RESULTS: Of 30 643 participants (50.8% male), 7.5% were born preterm (before 37 weeks gestation) and 92.5% were term born (between 37 and 42 weeks gestation). In the pooled data using multivariate adaptive regression splines, IQ linearly increased by 4.2 points as BWPs increased from the first to the 69th percentile before completely plateauing. For gestational age, IQ linearly increased by 1.3 points per week up until 32 weeks, with the association reducing to 0.3 points per week after 32 weeks. The association of BWP with IQ was not moderated by gestational age. For term-born infants, the estimated IQ score was only clinically meaningfully lower than average when birth weight was below the third percentile. Consistent results were found when instead using multivariable regression where gestational age and BWPs were categorized into groups.

CONCLUSIONS AND RELEVANCE: In this cohort study, lower BWPs and gestational age were independently associated with lower IQ. For term-born infants, a cutoff of the third percentile would be more appropriate than the traditionally used 10th percentile when the aim is estimating meaningful cognitive differences.

PMID:37651137 | DOI:10.1001/jamanetworkopen.2023.31815

JAMA Oncol. 2023 Aug 31. doi: 10.1001/jamaoncol.2023.3295. Online ahead of print.

ABSTRACT

IMPORTANCE: Although the combination of nivolumab plus ipilimumab has unquestionable benefit over nivolumab monotherapy in advanced melanoma, currently no summative analyses have compared the combination with nivolumab monotherapy for advanced cancers other than melanoma.

OBJECTIVE: To examine whether the addition of ipilimumab to standard-dose nivolumab safely improves clinical outcomes in patients with advanced cancers other than melanoma.

DATA SOURCES: Electronic databases (PubMed, EBSCO Information Services, Embase, and Cochrane Library) were systematically searched for studies of standard-dose nivolumab plus ipilimumab vs nivolumab alone in the treatment of advanced cancers other than melanoma published from database inception to October 31, 2022.

STUDY SELECTION: Eight studies (total patients, 1727; nivolumab plus ipilimumab group, 854; nivolumab monotherapy group, 873) met the selection criteria. Patients had squamous cell lung cancer, non-small cell lung cancer with programmed death ligand 1 level of 1% or higher, small cell lung cancer, pleural mesothelioma, urothelial carcinoma, esophagogastric carcinoma, sarcoma, or glioblastoma multiforme.

DATA EXTRACTION AND SYNTHESIS: For comparison of overall survival (OS) and progression-free survival (PFS) outcomes, estimation of log(hazard ratios [HRs]) and SEs was initially performed for OS and PFS of each included study based on summary statistics extracted from individual Kaplan-Meier curves. Inverse-variance weighting was then used to compute pooled HRs (95% CIs). For comparison of dichotomous data (treatment-related grade 3 to 4 adverse events and discontinuations), odds ratios (ORs) were used, and the Mantel-Haenszel method was used to estimate pooled ORs (95% CIs).

RESULTS: Treatment with nivolumab plus ipilimumab was not associated with improvement in OS over treatment with nivolumab alone (pooled HR, 0.95; 95% CI, 0.85-1.06; P = .36), with 4 of the 8 studies having numerically lower median OS with the combination. Nivolumab plus ipilimumab combination therapy was associated with marginal, but not clinically meaningful, improvement in PFS over nivolumab alone (pooled HR, 0.88; 95% CI, 0.79-0.98; P = .02). The combination was associated with substantially higher treatment-related grade 3 to 4 adverse events (pooled OR, 1.84; 95% CI, 1.47-2.31; P < .001) and treatment-related discontinuations (pooled OR, 1.96; 95% CI, 1.44-2.65; P < .001). This finding was recapitulated in meta-analyses of individual grade 3 to 4 adverse events of hepatotoxicity, gastrointestinal toxicity, pneumonitis, endocrine dysfunction, dermatitis, fatigue.

CONCLUSIONS AND RELEVANCE: In this meta-analysis of 8 advanced cancers other than melanoma, the differences detected in OS and PFS between nivolumab plus ipilimumab and nivolumab were not clinically meaningful (even though statistical significance was detected in PFS). Treatment-related higher-grade toxicity and discontinuations were substantially higher with the combination therapy. The data indicate that investigations of anti-programmed death 1 (PD1) plus anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapies in any nonmelanoma advanced cancer should be conducted along with anti-PD1 monotherapy to ensure that the net effect of the addition of anti-CTLA-4 to anti-PD1 can be clearly established for that cancer and setting and that unnecessary CTLA-4 inhibition with related toxic effects (both clinical and financial) can be avoided.

PMID:37651124 | DOI:10.1001/jamaoncol.2023.3295

JAMA. 2023 Aug 31. doi: 10.1001/jama.2023.14530. Online ahead of print.

ABSTRACT

IMPORTANCE: Psilocybin shows promise as a treatment for major depressive disorder (MDD).

OBJECTIVE: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD.

DESIGN, SETTING, AND PARTICIPANTS: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days’ duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing.

INTERVENTIONS: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment.

RESULTS: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs.

CONCLUSIONS AND RELEVANCE: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03866174.

PMID:37651119 | DOI:10.1001/jama.2023.14530

J Racial Ethn Health Disparities. 2023 Aug 31. doi: 10.1007/s40615-023-01776-2. Online ahead of print.

ABSTRACT

BACKGROUND: Disparities within clinical trial enrollment are well-documented, reducing the generalizability of results. Although nearly 30 years have passed since Congress passed the NIH Revitalization Act to encourage the participation of minoritized populations in clinical trials, these patients continue to be underrepresented. This study aimed to investigate lung cancer clinical trial enrollment disparities for race/ethnicity, sex, and age.

METHODS: We queried the National Institutes of Health: US National Library of Medicine database of clinical trials for all US-based lung cancer clinical trials completed between 2004 and 2021 and collected data on race and ethnicity, gender, and age breakdown. This data was compared to Surveillance, Epidemiology, and End Results (SEER) database data. Independent sample t-tests and Kruskal-Wallis’s approach were used to analyze the data.

RESULTS: Of 311 eligible trials with exclusive US enrollment, 136 (44%) reported race and ethnicity breakdown for the patient cohort representing 9869 patients. Hispanic, Non-Hispanic American Indian/Alaska Native, Non-Hispanic Black, and Non-Hispanic Unreported participants were underrepresented (p = 0.001, p = 0.005, p = 0.014, p = 0.002, respectively). Non-Hispanic White participants were overrepresented (p = 0.018). Disparities worsened from 2017 to 2021 for Hispanic patients (p = 0.03). No significant differences were found for sex or age.

CONCLUSIONS: Disparities for clinical lung cancer trial enrollment have not shown statistically significant improvement since 2004, and representation remains unequal, especially for racial and ethnic minorities.

PMID:37651069 | DOI:10.1007/s40615-023-01776-2

Acad Psychiatry. 2023 Aug 31. doi: 10.1007/s40596-023-01842-1. Online ahead of print.

ABSTRACT

OBJECTIVE: This pilot study compared a novel communication strategy, the positive approach to the psychiatric interview, with the traditional approach to see if the positive approach can be taught to psychiatric residents; reproduced with standardized patients; measured with a structured scale, the “Positive Approach Outcome Measure,” by blinded raters; and used to improve rapport (assessed with the Bond score), a key driver of engagement.

METHODS: Thirty psychiatric residents were randomly assigned to conduct two psychiatric interviews with standardized patients. The standardized patients completed the Working Alliance Inventory-Short Revised, an assessment of the therapeutic alliance. T tests and linear regression examined the effect of the training on the outcome of interest, the Bond score.

RESULTS: The Bond scores for the positive approach group (M = 19.27, SD = 2.87) and the traditional approach group (M = 16.90, SD = 3.44) were statistically significantly different (p = 0.05). All residents trained in the positive approach received a positive score on the Positive Approach Outcome Measure while none of the traditional approach-trained residents attained the threshold. The inter-rater reliability for the blinded raters was high (0.857), as was the intra-rater reliability (1.0).

CONCLUSIONS: The positive approach can be taught to residents and reproduced consistently and was associated with improvement in a key driver of treatment engagement: rapport. The positive approach may be an important, inexpensive intervention to improve treatment engagement and ultimately treatment outcomes.

PMID:37651038 | DOI:10.1007/s40596-023-01842-1

Environ Sci Pollut Res Int. 2023 Aug 31. doi: 10.1007/s11356-023-29569-4. Online ahead of print.

ABSTRACT

The traditional Environmental Kuznets Curve (EKC) theory, which establishes a relationship between economic growth and a select number of pollutants, does not fully capture the broad and nuanced impacts on environmental qualityThis research examines the implications of decomposed economic growth by considering the separate contributions of scale, composition, and technique effects on environmental health and ecosystem vitality. The research spans 121 countries from 2001-2019, using robust statistical methods, including Driscoll-Kraay standard error, fully modified ordinary least squares, and panel quantile estimation techniques. The study reveals complex relationships that depend on countries’ income levels. A predominantly positive and non-linear relationship between the scale effect and environmental health is observed for the full sample of countries and for low-income countries. The scale effect also shows a non-linear and predominantly positive relationship with ecosystem vitality in lower-middle-income, upper-middle-income, and high-income countries. The association between the composition effect and environmental health is inverted U-shaped in lower-middle-income countries, while it is mostly negative and non-linear in low-income and high-income countries. For ecosystem vitality, the composition effect shows a negative, non-linear relationship in all sampled countries, but a positive, non-linear relationship in higher-income countries. The relationship between the technology effect and environmental health is largely positive and non-linear in all sampled countries, lower-middle-income countries, upper-middle-income countries, and higher-income countries. However, the relationship is negative in lower-middle-income countries. These results have important policy implications. Governments are encouraged to adopt renewable, sustainable, and low-carbon technologies to address the scale effect. In addition, the formulation and enforcement of stringent environmental regulations for polluting industries is crucial, given the significant impact of the composition effect.

PMID:37651011 | DOI:10.1007/s11356-023-29569-4