Tag: nevin manimala

JAMA Oncol. 2023 Jul 6. doi: 10.1001/jamaoncol.2023.2132. Online ahead of print.

ABSTRACT

IMPORTANCE: Although immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and PD-1 ligand 1 have improved the outcome for many cancer types, the majority of patients fails to respond to ICI monotherapy. Hypofractionated radiotherapy has the potential to improve the therapeutic ratio of ICIs.

OBJECTIVE: To assess the addition of radiotherapy to ICIs compared with ICI monotherapy in patients with advanced solid tumors.

DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicenter, randomized phase 2 trial was conducted in 5 Belgian hospitals and enrolled participants between March 2018 and October 2020. Patients 18 years or older with locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, or non-small cell lung carcinoma were eligible. A total of 99 patients were randomly assigned to either the control arm (n = 52) or the experimental arm (n = 47). Of those, 3 patients (1 in the control arm vs 2 in the experimental arm) withdrew consent and thus were not included in the analysis. Data analyses were performed between April 2022 and March 2023.

INTERVENTIONS: Patients were randomized (1:1) to receive anti-PD-1/PD-1 ligand 1 ICIs alone as per standard of care (control arm) or combined with stereotactic body radiotherapy 3 × 8 gray to a maximum of 3 lesions prior to the second or third ICI cycle, depending on the frequency of administration (experimental arm). Randomization was stratified according to tumor histologic findings and disease burden (3 and fewer or more than 3 cancer lesions).

MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS) as per immune Response Evaluation Criteria in Solid Tumors. Key secondary end points included overall survival (OS), objective response rate, local control rate, and toxic effects. Efficacy was assessed in the intention-to-treat population, while safety was evaluated in the as-treated population.

RESULTS: Among 96 patients included in the analysis (mean age, 66 years; 76 [79%] female), 72 (75%) had more than 3 tumor lesions and 65 (68%) had received at least 1 previous line of systemic treatment at time of inclusion. Seven patients allocated to the experimental arm did not complete the study-prescribed radiotherapy course due to early disease progression (n = 5) or intercurrent illness (n = 2). With a median (range) follow-up of 12.5 (0.7-46.2) months, median PFS was 2.8 months in the control arm compared with 4.4 months in the experimental arm (hazard ratio, 0.95; 95% CI, 0.58-1.53; P = .82). Between the control and experimental arms, no improvement in median OS was observed (11.0 vs 14.3 months; hazard ratio, 0.82; 95% CI, 0.48-1.41; P = .47), and objective response rate was not statistically significantly different (22% vs 27%; P = .56), despite a local control rate of 75% in irradiated patients. Acute treatment-related toxic effects of any grade and grade 3 or higher occurred in 79% and 18% of patients in the control arm vs 78% and 18% in the experimental arm, respectively. No grade 5 adverse events occurred.

CONCLUSIONS AND RELEVANCE: This phase 2 randomized clinical trial demonstrated that while safe, adding subablative stereotactic radiotherapy of a limited number of metastatic lesions to ICI monotherapy failed to show improvement in PFS or OS.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03511391.

PMID:37410476 | DOI:10.1001/jamaoncol.2023.2132

JAMA Netw Open. 2023 Jul 3;6(7):e2321798. doi: 10.1001/jamanetworkopen.2023.21798.

ABSTRACT

IMPORTANCE: Psychiatric boarding occurs when patients needing intensive psychiatric services who are already under clinical supervision experience delays in their admission to psychiatric facilities. Initial reports have suggested that the US had a psychiatric boarding crisis during the COVID-19 pandemic; however, little is known about the consequences of this crisis for publicly insured youths.

OBJECTIVE: To estimate pandemic-associated changes in psychiatric boarding rates and discharge modalities for people aged 4 to 20 years who accessed psychiatric emergency services (PES) through a mobile crisis team (MCT) evaluation and were covered by Medicaid or health safety net programs.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study used data from the MCT encounters of a multichannel PES program in Massachusetts. A total of 7625 MCT-initiated PES encounters with publicly insured youths who lived in Massachusetts between January 1, 2018, and August 31, 2021, were assessed.

MAIN OUTCOMES AND MEASURES: Encounter-level outcomes (psychiatric boarding status, repeat visits, and discharge disposition) during a prepandemic period (January 1, 2018, to March 9, 2020) were compared with outcomes during a pandemic period (March 10, 2020, to August 31, 2021). Descriptive statistics and multivariate regression analysis were used.

RESULTS: Among 7625 MCT-initiated PES encounters, the mean (SD) age of publicly insured youths was 13.6 (3.7) years; most youths identified as male (3656 [47.9%]), were of Black race (2725 [35.7%]) or Hispanic ethnicity (2708 [35.5%]), and spoke English (6941 [91.0%]). During the pandemic period, the mean monthly boarding encounter rate was 25.3 percentage points higher than the prepandemic period. After adjustment for covariates, the odds of an encounter resulting in boarding doubled during the pandemic (adjusted odds ratio [AOR], 2.03; 95% CI, 1.82-2.26; P < .001), and boarding youths were 64% less likely to be discharged to inpatient psychiatric care (AOR, 0.36; 95% CI, 0.31-0.43; P < .001). Publicly insured youths who boarded during the pandemic had significantly higher rates of 30-day readmissions (incidence rate ratio, 2.17; 95% CI, 1.88-2.50; P < .001). Boarding encounters during the pandemic were significantly less likely to end in discharge to inpatient psychiatric units (AOR, 0.36; 95% CI, 0.31-0.43; P < .001) or community-based acute treatment facilities (AOR, 0.70; 95% CI, 0.55-0.90; P = .005).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, publicly insured youths were more likely to experience psychiatric boarding during the COVID-19 pandemic and, if boarding, were less likely to transfer to a 24-hour level of care. These findings suggest that psychiatric service programs for youths were not prepared to support the levels of acuity and demand that emerged from the pandemic.

PMID:37410466 | DOI:10.1001/jamanetworkopen.2023.21798

JAMA Netw Open. 2023 Jul 3;6(7):e2321947. doi: 10.1001/jamanetworkopen.2023.21947.

ABSTRACT

IMPORTANCE: Data suggest that the opioid crisis in North America has recently been reflected in opioid-related mortality among youths. Despite recommendation for its use, youths encounter barriers to accessing OAT, including stigma, burden of witnessed dosing, and lack of availability of youth-oriented services and prescribers comfortable treating this population.

OBJECTIVE: To compare rates of opioid agonist treatment (OAT) and opioid-related mortality between youths aged 15 to 24 years and adults aged 25 to 44 years in Ontario, Canada, over time.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis of rates of OAT and opioid-related deaths between 2013 and 2021 used data obtained from the Ontario Drug Policy Research Network, Public Health Ontario, and Statistics Canada. Individuals included in the analysis were aged 15 to 44 years and residing in Ontario, the most populous province in Canada.

EXPOSURES: Youths aged 15 to 24 years compared with adults aged 25 to 44 years.

MAIN OUTCOMES AND MEASURES: OAT (methadone, buprenorphine, and slow-release oral morphine) per 1000 population and opioid-related deaths per 100 000 population.

RESULTS: Between 2013 and 2021, 1021 youths aged 15 to 24 years died from opioid toxicity; 710 were male (69.5%). In the final year of the study period, 225 youths (146 male [64.9%]) died from opioid toxicity, and 2717 (1494 male [55.0%]) were dispensed OAT. Over the study period, the rate of opioid-related deaths among youths in Ontario increased 369.2% from 2.6 to 12.2 per 100 000 population (48 to 225 total deaths) and the rate of OAT use decreased 55.9% from 3.4 to 1.5 per 1000 (6236 to 2717 individuals). For adults aged 25 to 44 years, the rate of opioid-related deaths increased 371.8% from 7.8 to 36.8 per 100 000 (283 to 1502 deaths), and the rate of OAT increased 27.8% from 7.9 to 10.1 per 1000 population (28 667 to 41 200 individuals). Trends for youths and adults persisted across both sexes.

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that opioid-related deaths are increasing among youths while OAT use is paradoxically declining. The reasons for these observed trends require further investigation, including a consideration of changing trends in opioid use and opioid use disorder among youths, barriers to OAT, and opportunities to optimize care and reduce harms for youths who use substances.

PMID:37410463 | DOI:10.1001/jamanetworkopen.2023.21947

JAMA Netw Open. 2023 Jul 3;6(7):e2321971. doi: 10.1001/jamanetworkopen.2023.21971.

ABSTRACT

IMPORTANCE: Anticoagulation management services (AMSs; ie, warfarin clinics) have evolved to include patients treated with direct oral anticoagulants (DOACs), but it is unknown whether DOAC therapy management services improve outcomes for patients with atrial fibrillation (AF).

OBJECTIVE: To compare outcomes associated with 3 DOAC care models for preventing adverse anticoagulation-related outcomes among patients with AF.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 44 746 adult patients with a diagnosis of AF who initiated oral anticoagulation (DOAC or warfarin) between August 1, 2016, and December 31, 2019, in 3 Kaiser Permanente (KP) regions. Statistical analysis was conducted from August 2021 through May 2023.

EXPOSURES: Each KP region used an AMS to manage warfarin but used distinct approaches to DOAC care: (1) usual care (UC) by the prescribing clinician, (2) UC plus an automated population management tool (PMT), or (3) pharmacist-managed AMS care. Propensity scores and inverse probability of treatment weights (IPTWs) were estimated. Direct oral anticoagulant care models were first indirectly compared using warfarin as a common comparator within each region and then directly compared across regions.

MAIN OUTCOMES AND MEASURES: Patients were followed up until the first occurrence of an outcome (composite of thromboembolic stroke, intracranial hemorrhage, other major bleeding, or death), discontinuation of KP membership, or December 31, 2020.

RESULTS: Overall, 44 746 patients were included: 6182 in the UC care model (3297 DOAC; 2885 warfarin), 33 625 in the UC plus PMT care model (21 891 DOAC; 11 734 warfarin), and 4939 in the AMS care model (2089 DOAC; 2850 warfarin). Baseline characteristics (mean [SD] age, 73.1 [10.6] years, 56.1% male, 67.2% non-Hispanic White, median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, female sex] score of 3 [IQR, 2-5]) were well balanced after IPTW. Over a median follow-up of 2 years, patients who received the UC plus PMT or AMS care model did not have significantly better outcomes than those who received UC. The incidence rate of the composite outcome was 5.4% per year for DOAC and 9.1% per year for warfarin for those in the UC group, 6.1% per year for DOAC and 10.5% per year for those in the UC plus PMT group, and 5.1% per year for DOAC and 8.0% per year for those in the AMS group. The IPTW-adjusted hazard ratios (HRs) for the composite outcome comparing DOAC vs warfarin were 0.91 (95% CI, 0.79-1.05) in the UC group, 0.85 (95% CI, 0.79-0.90) in the UC plus PMT group, and 0.84 (95% CI, 0.72-0.99) in the AMS group (P = .62 for heterogeneity across care models). When directly comparing patients receiving DOAC, the IPTW-adjusted HR was 1.06 (95% CI, 0.85-1.34) for the UC plus PMT group vs the UC group and 0.85 (95% CI, 0.71-1.02) for the AMS group vs the UC group.

CONCLUSIONS AND RELEVANCE: This cohort study did not find appreciably better outcomes for patients receiving DOAC who were managed by either a UC plus PMT or AMS care model compared with UC.

PMID:37410461 | DOI:10.1001/jamanetworkopen.2023.21971

Personal Disord. 2023 Jul 6. doi: 10.1037/per0000632. Online ahead of print.

ABSTRACT

The Alternative Model of Personality Disorders (AMPD), introduced in Section III of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013), was proposed as a new operationalization of personality disorders (PDs) aiming to overcome the several limitations of the traditional symptom-based model (Waugh et al., 2017; Zimmerman et al., 2019). In the AMPD, PDs are defined by two-dimensional criteria (the level of personality functioning and maladaptive personality traits), but as a hybrid model, it also allows for categorical assessment of PDs (i.e., “hybrid types”) to facilitate continuity with clinical practice. The present study aimed to provide normative data for two widely used instruments assessing Criterion A (Level of Personality Functioning Scale-Self-Report; Morey, 2017) and B (Personality Inventory for DSM-5; Krueger et al., 2012) in a large populational French-Canadian sample. Regarding the categorical assessment, Gamache et al. (2022) recently tested scoring approaches for extracting the PD hybrid types from dimensional measures of the AMPD. In the present study, these approaches were used to estimate prevalence rates for these PD hybrid types in two samples. In the populational sample, results showed that prevalence rates varied from 0.2% (antisocial PDs) to 3.0% (trait-specified PDs), with an overall prevalence of 5.9% to 6.1% for any PD hybrid type. Prevalence was higher in men than in women in the populational sample, but the contrary was observed in the at-risk sample. Prevalence was higher in younger adults than in middle-aged and older adults. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37410427 | DOI:10.1037/per0000632

Health Psychol. 2023 Jul 6. doi: 10.1037/hea0001303. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the effects of mindfulness training for primary care (MTPC), an integrated warm mindfulness training program, on emotion regulation and its relationship with health behavior change. Interventions that improve self-regulation, particularly emotion regulation, are needed for the self-management of comorbid chronic physical and mental illnesses. Mindfulness-based interventions (MBIs) may impact self-regulation and facilitate health behavior change.

METHOD: A randomized controlled comparative effectiveness trial was conducted in a population of adult primary care patients to evaluate the impact of MTPC versus a low-dose mindfulness comparator (LDC) on self-reported difficulties in emotion regulation (DERS) total score and other assays of self-regulation at baseline, Weeks 8 and 24. Self-reported action plan initiation was reported between Weeks 8 and 10. Participants had diagnoses of anxiety, depression, or stress-related disorders. MTPC is an 8-week insurance-reimbursable warm MBI designed to cultivate mindfulness and self-compassion and to catalyze chronic illness self-management related health behavior change.

RESULTS: Compared to LDC, MTPC participants had statistically significant reductions in DERS total score at 8 weeks (d = -0.59, β = -12.98, 95% CI [-23.3 to -2.6]; p = .01) and 24 weeks (d = -0.61, β = -13.35, [-24.3, -2.4]; p = .02). Compared to 38% for LDC, 63% of MTPC participants successfully initiated their action plan within 3 weeks (OR = 2.87, [1.1, 7.9]; p = .04).

CONCLUSIONS: This randomized controlled trial demonstrated MTPC enhanced emotion regulation and facilitated initiation of chronic illness self-management and health behavior change among primary care patients with anxiety, depression, and stress-related disorders, replicating previous reports. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37410421 | DOI:10.1037/hea0001303

Can J Public Health. 2023 Jul 6. doi: 10.17269/s41997-023-00789-y. Online ahead of print.

ABSTRACT

OBJECTIVES: During the first wave of COVID-19 in Québec, healthcare workers (HCWs) represented 25% of the cases in Montréal. A study was conducted to describe SARS-CoV-2-infected HCWs in Montréal, and certain workplace and household characteristics. Secondary objectives included estimating the associations between having had access to personal protective equipment (PPE) and training, and following self-isolation recommendations, and certain sociodemographic and workplace characteristics.

METHODS: A cross-sectional study was conducted, based on a stratified random sample, among Montréal HCWs who tested positive for SARS-CoV-2 between March and July 2020. A total of 370 participants answered a telephone-administered questionnaire. Descriptive statistics were conducted, followed by log binomial regressions to estimate the associations.

RESULTS: Study participants were mostly female (74%), born outside of Canada (65%), and identified as Black, Indigenous, and People of Colour (BIPOC; 63%). In terms of healthcare positions, most were orderlies (40%) or registered nurses (20%). Half (52%) of the participants reported having had insufficient access to PPE and 30% reported having received no training related to SARS-CoV-2 infection prevention, with large proportions being BIPOC women. Working evening or night shifts decreased chances of having had sufficient access to PPE (OR 0.50; 0.30-0.83).

CONCLUSION: This study describes the profile of the HCWs who were infected during the first wave of the pandemic in Montréal. Recommendations include collecting comprehensive sociodemographic data on SARS-CoV-2 infections and ensuring equitable access to infection prevention and control training and PPE during health crises, particularly those at highest risk of exposure.

PMID:37410364 | DOI:10.17269/s41997-023-00789-y

Mol Biol Rep. 2023 Jul 6. doi: 10.1007/s11033-023-08636-6. Online ahead of print.

ABSTRACT

BACKGROUND: The conidial Ascomycota fungus Wilsonomyces carpophilus causing shot hole in stone fruits is a major constraint in the production of stone fruits worldwide. Shothole disease symptoms appear on leaves, fruits, and twigs. Successful isolation of the pathogen from different hosts on synthetic culture medium is a time consuming and tedious procedure for identification of the pathogen based on morpho-cultural characterization.

METHODS AND RESULTS: The present research was carried out to develop a successful PCR based early detection protocol for the shot hole disease of stone fruits, viz., peach, plum, apricot, cherry, and almond using the pathogen specific SSR markers developed from the Wilsonomyces carpophilus genome using Genome-wide Microsatellite Analysing Tool package (GMATA) software. Diseased leaf samples of different stone fruits were collected from the SKUAST-K orchard and the pathogen was isolated on potato dextrose agar (PDA) medium and maintained on Asthana and Hawkers’ medium with a total of 50 pathogen isolates comprised of 10 isolates each from peach, plum, apricot, cherry and almond. The DNA was extracted from both healthy and infected leaf samples of different stone fruits. The DNA was also extracted from the isolated pathogen cultures (50 isolates). Out of 2851 SSR markers developed, 30 SSRs were used for the successful amplification of DNA extracted from all the 50 pathogen isolates. These SSRs were used for the amplification DNA from shot hole infected leaf samples of different stone fruits, but the amplification was not observed in the control samples (DNA from healthy leaves), thus confirming the detection of this disease directly from the shot hole infected samples using PCR based SSR markers. To our knowledge, this forms the first report of SSR development for the Wilsonomyces carpophilus and their validation for the detection of shot hole disease directly from infected leaves.

CONCLUSION: PCR based SSR makers were successfully developed and used for the detection of Wilsonomyces carpophilus causing shot hole disease in stone fruits including almond in nuts for the first time. These SSR markers could successfully detect the pathogen directly from the infected leaves of stone fruits namely peach, plum, apricot and cherry including almond from the nuts.

PMID:37410347 | DOI:10.1007/s11033-023-08636-6

Environ Sci Pollut Res Int. 2023 Jul 6. doi: 10.1007/s11356-023-27605-x. Online ahead of print.

ABSTRACT

Water is an essential element in nature. It is used in drinking, irrigation, and industry mainly. Human health is directly linked to groundwater quality and is affected by poor groundwater quality caused by excessive fertilizer application and unhygienic circumstances. Because of increased pollution, investigating the water quality became a point of research for many researchers. There are numerous approaches to assessing water quality, and statistical methods are essential among them. This review paper discusses Multivariate Statistical Techniques, including Cluster Analysis, Principal Component Analysis, Factor Analysis, Geographical Information System, and Analysis of Variance, to name a few. We have presented the significance of each method concisely and how it is being used. In addition, an extensive table is prepared to demonstrate the individual technique along with the computational tool, the type of water bodies, and their respective regions. The advantages and disadvantages of the statistical techniques are also discussed therein. It is found that Principal Component Analysis and Factor Analysis are widely explored techniques.

PMID:37410329 | DOI:10.1007/s11356-023-27605-x

Int Urol Nephrol. 2023 Jul 6. doi: 10.1007/s11255-023-03696-w. Online ahead of print.

ABSTRACT

PURPOSE: End-stage renal disease patients on chronic hemodialysis (HD) have a shortened life expectancy compared to the general population. The aim of this study was to evaluate a possible link between three new and emerging factors in renal pathophysiology: Klotho protein, telomere length in peripheral blood mononuclear cells (TL) and redox status parameters before HD (bHD) and after HD (aHD), and to test mortality prediction capability of these emerging parameters in a population of HD patients.

METHODS: The study included 130 adult patients with average age 66 (54-72), on HD (3 times per week; 4-5 h per session). Klotho level, TL, routine laboratory parameters, dialysis adequacy and redox status parameters: advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), superoxide anion (O₂^.-), malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl group content (SHG), and superoxide dismutase (SOD) were determined.

RESULTS: Klotho concentration was significantly higher aHD; 68.2 (22.6-152.9) vs. bHD 64.2 (25.5-119.8) (p = 0.027). The observed increase in TL was not statistically significant. AOPP, PAB, SHG, and SOD activity were significantly increased aHD (p > 0.001). The patients with the highest mortality risk score (MRS) had significantly higher PAB bHD (p = 0.002). Significantly lower O₂^.- (p < 0.001), SHG content (p = 0.072), and IMA (p = 0.002) aHD were found in patients with the lowest MRS values. Principal component analysis revealed redox balance-Klotho factor as a significant predictor of high mortality risk (p = 0.014).

CONCLUSION: Decreased Klotho and TL attrition as well as redox status disturbance could be connected with higher mortality rate in HD patients.

PMID:37410303 | DOI:10.1007/s11255-023-03696-w