Category: Nevin Manimala

J Am Vet Med Assoc. 2023 Apr 18:1-7. doi: 10.2460/javma.23.01.0027. Online ahead of print.

ABSTRACT

OBJECTIVE: Assess efficacy of ropinirole versus apomorphine in inducing vomiting in dogs.

ANIMALS: 279 client-owned dogs with known or suspected ingestion of a foreign material (n = 129) or toxin (150) between August 2021 and February 2022.

PROCEDURES: In this non-randomized non-controlled clinical trial, ropinirole topical ophthalmic solution was applied to dogs’ eyes, with a target dose of 3.75 mg/m2. A second dose was administered after 15 minutes based on clinician discretion. Reversal with metoclopramide was provided based on clinician discretion. Results of ropinirole’s efficacy were compared to previous literature assessing the efficacy of apomorphine.

RESULTS: Of 279 dogs, 255 (91.4%) vomited after ropinirole administration, including 116 of the 129 dogs (89.9%) dogs that ingested foreign material and 139 of the 150 dogs (92.7%) that ingested toxins. Success of emesis did not differ between groups. With a single dose of ropinirole, 78.9% produced vomit. Fifty-nine dogs received 2 doses of ropinirole, resulting in 79.7% that produced vomit. Overall, 74.2% of the dogs vomited all the expected ingested material. Average time to emesis was 11.0 minutes with 50% of dogs vomiting within 7 to 18 minutes. Adverse effects were observed for 17.0% of dog and were self-limiting. Ropinirole was less effective than apomorphine in inducing vomiting (91.4% ropinirole, 95.6% apomorphine [P < .0001]) and equally effective at evacuating all ingested material (74.2% ropinirole, 75.6% apomorphine [P = .245]).

CLINICAL RELEVANCE: Ropinirole ophthalmic solution is a safe and effective emetic for use in dogs. It has a small but statistically significant decrease in efficacy compared to IV apomorphine.

PMID:37072118 | DOI:10.2460/javma.23.01.0027

J Card Fail. 2023 Apr 16:S1071-9164(23)00142-2. doi: 10.1016/j.cardfail.2023.04.003. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammation is a key driver of heart failure (HF) with preserved left ventricular ejection fraction (LVEF). AZD4831 inhibits extracellular myeloperoxidase, reduces inflammation and improves microvascular function in preclinical disease models.

METHODS: In this double-blind phase 2a study (SATELLITE; NCT03756285), patients with symptomatic HF, LVEF ≥40%, and elevated B-type natriuretic peptides were randomized 2:1 to once-daily oral AZD4831 5 mg or placebo for 90 days. We aimed to assess target engagement (primary endpoint: myeloperoxidase specific activity) and safety of AZD4831.

RESULTS: Due to COVID-19, the study was terminated early after randomizing 41 patients (median age, 74.0 years; 53.7% male). Myeloperoxidase activity was reduced by >50% from baseline to day 30 and 90 in the AZD4831 group, with a placebo-adjusted reduction of 75% (95% confidence interval: 48, 88; nominal P <0.001). No improvements were noted in secondary/exploratory endpoints, apart from a trend in Kansas City Cardiomyopathy Questionnaire overall summary score. No deaths or treatment-related serious adverse events occurred. AZD4831 treatment-related adverse events were generalized maculopapular rash, pruritus and diarrhoea (all n=1).

CONCLUSIONS: AZD4831 inhibited myeloperoxidase and was well tolerated in patients with HF and LVEF ≥40%. Efficacy findings were exploratory due to early termination but warrant further clinical investigation of AZD4831.

LAY SUMMARY: Few treatments are available for patients with the forms of heart failure known as ‘heart failure with preserved or mildly reduced ejection fraction’. Current treatments do not target inflammation, which may play an important role in this condition. We tested a new drug called AZD4831 (mitiperstat), which reduces inflammation by inhibiting the enzyme myeloperoxidase. Among the 41 patients in our clinical trial, AZD4831 had a good safety profile and inhibited myeloperoxidase by the expected amount. Results mean we can conduct further trials to see whether AZD4831 reduces the symptoms of heart failure and improves patients’ ability to take physical exercise.

PMID:37072105 | DOI:10.1016/j.cardfail.2023.04.003

Pediatr Phys Ther. 2023 Apr 19. doi: 10.1097/PEP.0000000000001014. Online ahead of print.

ABSTRACT

PURPOSE: Physical therapists at an outpatient pediatric facility developed and implemented an Intensity Program for children with movement challenges. The program was initiated on the basis of best evidence, parent advocacy, and clinician expertise. The purpose of this investigation is to analyze outcome data gathered from the program since 2012 to determine the effect of the program along with any specific child characteristics that were more likely to lead to positive outcomes.

METHODS: A variety of outcome data were analyzed to compare preprogram performance with postprogram performance.

RESULTS: Program participants made statistically significant and clinically important improvement in most outcome measures. Parents were highly satisfied with the program, including 98% of respondents who indicated that they would like to repeat their participation in the program.

CONCLUSIONS: The results of this investigation suggest that many children with movement challenges are likely to benefit from participation in an Intensity Program.

PMID:37071878 | DOI:10.1097/PEP.0000000000001014

Prostate. 2023 Apr 18. doi: 10.1002/pros.24512. Online ahead of print.

ABSTRACT

BACKGROUND: We performed a secondary analysis of ACIS study to determine if synchronous versus metachronous metastatic presentation has any association with survival and treatment response to dual androgen receptor axis-targeted therapy (ARAT) in docetaxel naïve metastatic castrate resistant prostate cancer (mCRPC).

METHODOLOGY: In this phase III randomized controlled trial, docetaxel naïve mCRPC patients were randomized to either apalutamide or placebo combined with abiraterone and prednisone. Multivariable Cox regression models were applied to determine the adjusted association of M-stage with radiographic progression-free survival (rPFS) and overall survival (OS). To determine the heterogeneity of treatment effect based on metastatic stage (M-stage) at presentation, Cox regression was applied with interaction terms between M-stage and treatment.

RESULTS: Among 972 patients, 432 had M0, 334 had M1, while M-stage at presentation was unknown in 206. There was no association of M-stage at presentation with rPFS in patients with prior local therapy (LT) (hazard ratio for M1-stage: 1.22 [95% confidence interval: 0.82-1.82]; unknown: 1.03 [0.77-1.38]) or without prior LT (M1-stage: 0.87 [0.64-1.19]; unknown: 1.15 [0.77-1.72]) with no significant heterogeneity. Similarly, there was no association of M-stage with OS in patients with prior LT (M1-stage: 1.04 [0.81-1.33]; unknown: 0.98 [0.79-1.21]) or without prior LT (M1-stage: 0.95 [0.70-1.29]; unknown: 1.17 [0.80-1.71]) with no significant heterogeneity. Based on M-stage at presentation, we did not find any significant heterogeneity in treatment effect on rPFS (interaction p = 0.13), and OS (interaction p = 0.87).

CONCLUSION: M-stage at presentation had no association with survival in chemotherapy-naïve mCRPC. We did not find any statistically significant heterogeneity in efficacy of dual ARAT based on synchronous versus metachronous presentation.

PMID:37071764 | DOI:10.1002/pros.24512

Proc Natl Acad Sci U S A. 2023 Apr 25;120(17):e2215434120. doi: 10.1073/pnas.2215434120. Epub 2023 Apr 18.

ABSTRACT

This study aims to identify the timescale of suicidal thinking, leveraging real-time monitoring data and a number of different analytic approaches. Participants were 105 adults with past week suicidal thoughts who completed a 42-d real-time monitoring study (total number of observations = 20,255). Participants completed two forms of real-time assessments: traditional real-time assessments (spaced hours apart each day) and high-frequency assessments (spaced 10 min apart over 1 h). We found that suicidal thinking changes rapidly. Both descriptive statistics and Markov-switching models indicated that elevated states of suicidal thinking lasted on average 1 to 3 h. Individuals exhibited heterogeneity in how often and for how long they reported elevated suicidal thinking, and our analyses suggest that different aspects of suicidal thinking operated on different timescales. Continuous-time autoregressive models suggest that current suicidal intent is predictive of future intent levels for 2 to 3 h, while current suicidal desire is predictive of future suicidal desire levels for 20 h. Multiple models found that elevated suicidal intent has on average shorter duration than elevated suicidal desire. Finally, inferences about the within-person dynamics of suicidal thinking on the basis of statistical modeling were shown to depend on the frequency at which data was sampled. For example, traditional real-time assessments estimated the duration of severe suicidal states of suicidal desire as 9.5 h, whereas the high-frequency assessments shifted the estimated duration to 1.4 h.

PMID:37071683 | DOI:10.1073/pnas.2215434120

Proc Natl Acad Sci U S A. 2023 Apr 25;120(17):e2206527120. doi: 10.1073/pnas.2206527120. Epub 2023 Apr 18.

ABSTRACT

The evolution of the mitochondria was a significant event that gave rise to the eukaryotic lineage and most large complex life. Central to the origins of the mitochondria was an endosymbiosis between prokaryotes. Yet, despite the potential benefits that can stem from a prokaryotic endosymbiosis, their modern occurrence is exceptionally rare. While many factors may contribute to their rarity, we lack methods for estimating the extent to which they constrain the appearance of a prokaryotic endosymbiosis. Here, we address this knowledge gap by examining the role of metabolic compatibility between a prokaryotic host and endosymbiont. We use genome-scale metabolic flux models from three different collections (AGORA, KBase, and CarveMe) to assess the viability, fitness, and evolvability of potential prokaryotic endosymbioses. We find that while more than half of host-endosymbiont pairings are metabolically viable, the resulting endosymbioses have reduced growth rates compared to their ancestral metabolisms and are unlikely to gain mutations to overcome these fitness differences. In spite of these challenges, we do find that they may be more robust in the face of environmental perturbations at least in comparison with the ancestral host metabolism lineages. Our results provide a critical set of null models and expectations for understanding the forces that shape the structure of prokaryotic life.

PMID:37071674 | DOI:10.1073/pnas.2206527120

Nurs Open. 2023 Apr 18. doi: 10.1002/nop2.1751. Online ahead of print.

ABSTRACT

AIMS: To explore the university students’ attitude and the potential influencing factors to receive the coronavirus disease 2019 (COVID-19) vaccine in Sichuan Province, China.

DESIGN: A cross-sectional study.

METHODS: The self-designed questionnaire was distributed among university students online in June 2021. SPSS software was used for statistical analysis of the data. Descriptive statistics, Chi-square, two independent samples t-tests, one-way analysis of variance (ANOVA), multivariate linear regression, and content analysis were performed.

RESULTS: A total of 397 questionnaires were analysed, involving 316 (79.6%) respondents have received at least one dose of a COVID-19 vaccine and 81 (20.4%) have not taken the vaccine. The total mean score of university students’ vaccination attitude was 25.97 (standard deviation [SD] = 3.720), and the total scoring rate was 74.2%. Main factors influencing students’ attitude included education level, major, living style, with chronic disease or not, self-reported vaccination status, and number of medical units that can provide vaccination within 3 km of residence. Students were more willing to choose Chinese-manufactured vaccines (66.8%) and participate in collective vaccination programs organized by the school (71.3%). The desired vaccine protection period was 5-10 years (42.1%). The top three reasons for refusing the vaccine or vaccine hesitancy were as follows: concern about the side effects of vaccine (44.8%), lack of information about vaccine (31.0%), and concern about the efficacy of vaccine (29.3%).

CONCLUSION: In general, most of the participants had relatively high level of positive attitude to receive the COVID-19 vaccine. Nevertheless, more attention should be paid to postgraduate students, non-medical students, those living alone, those with chronic disease, those have not received the COVID-19 vaccine, and those living far away from the vaccination medical units. Findings of this study can help educational institutions in developing effective interventions to improve the vaccination rate in the university student population.

PMID:37071667 | DOI:10.1002/nop2.1751

PLoS One. 2023 Apr 18;18(4):e0284474. doi: 10.1371/journal.pone.0284474. eCollection 2023.

ABSTRACT

BACKGROUND: Primary care patients with obesity seldom receive effective weight management treatment in primary care settings. This study aims to understand PCPs’ perspectives on obesity treatment barriers and opportunities to overcome them.

STUDY DESIGN: This is an explanatory sequential mixed methods study in which survey data was collected and used to inform subsequent qualitative interviews.

SETTINGS AND PARTICIPANTS: PCPs who provide care to adult patients in an academic medical center in the Midwestern US.

METHODOLOGY: PCPs (n = 350) were invited by email to participate in an online survey. PCPs were subsequently invited to participate in semi-structured interviews to further explore survey domains.

ANALYTIC APPROACH: Survey data were analyzed using descriptive statistics. Interviews were analyzed using directed content analysis.

RESULTS: Among 107 survey respondents, less than 10% (n = 8) used evidence-based guidelines to inform obesity treatment decisions. PCPs’ identified opportunities to improve obesity treatment including (1) education on local obesity treatment resources (n = 78, 73%), evidence-based dietary counseling strategies (n = 67, 63%), and effective self-help resources (n = 75, 70%) and (2) enhanced team-based care with support from clinic staff (n = 53, 46%), peers trained in obesity medicine (n = 47, 44%), and dietitians (n = 58, 54%). PCPs also desired increased reimbursement for obesity treatment. While 40% (n = 39) of survey respondents expressed interest in obesity medicine training and certification through the American Board of Obesity Medicine, qualitative interviewees felt that pursuing training would require dedicated time (i.e., reduced clinical effort) and financial support.

CONCLUSIONS: Opportunities to improve obesity treatment in primary care settings include educational initiatives, use of team-based care models, and policy changes to incentivize obesity treatment. Primary care clinics or health systems should be encouraged to identify PCPs with specific interests in obesity medicine and support their training and certification through ABOM by reimbursing training costs and reducing clinical effort to allow for study and board examination.

PMID:37071660 | DOI:10.1371/journal.pone.0284474

Clin J Am Soc Nephrol. 2023 Apr 18. doi: 10.2215/CJN.0000000000000173. Online ahead of print.

ABSTRACT

BACKGROUND: For patients who initiate dialysis during a hospital admission and continue to require dialysis after discharge, outpatient dialysis management could be improved by better understanding the future likelihood of recovery to dialysis-independence and the competing risk of death.

METHODS: We derived and validated linked models to predict the subsequent recovery to dialysis-independence and death within one year of hospital discharge using a population-based cohort of 7,657 patients in Ontario, Canada. Predictive variables included age, comorbidities, length of hospital admission, intensive care status, discharge disposition, and pre-hospital admission estimated glomerular filtration rate and random urine urine albumin to creatinine ratio. Models were externally validated in 1,503 contemporaneous patients from Alberta, Canada. Both models were created using proportional hazards survival analysis, with the ‘Recovery Model’ using Fine-Gray methods. Probabilities generated from both models were used to develop 16 distinct Recovery or Death Outcomes (ReDO) risk groups.

RESULTS: ReDO risk groups in the derivation group had significantly distinct 1-year probabilities for recovery to dialysis-independence (1st Quartile: 10% [95%CI 9-11]; 4th Quartile: 73% [70-77]) and for death (1st Quartile: 12% [11-13]; 4th Quartile: 46% [43-50]). In the validation group, model discrimination was modest (c-statistics [95%CI] for recovery and for death quartiles were 0.70 [0.67-0.73] and 0.66 [0.62-0.69], respectively) but calibration was excellent (integrated calibration index [95%CI] was 7% [5-9] and 4% [2-6] for recovery and death, respectively).

CONCLUSIONS: The ReDO models generated accurate expected probabilities of recovery to dialysis-independence and death in patients who continued outpatient dialysis after initiating dialysis in hospital. An online tool based on the models is available at: https://qxmd.com/calculate/calculator_874 Click to follow link.”>https://qxmd.com/calculate/calculator_874.

PMID:37071648 | DOI:10.2215/CJN.0000000000000173

Cyberpsychol Behav Soc Netw. 2023 Apr;26(4):288-299. doi: 10.1089/cyber.2022.0228.

ABSTRACT

Meta-analyses have found that social cognition training (SCT) has large effects on the emotion recognition ability of people with a psychotic disorder. Virtual reality (VR) could be a promising tool for delivering SCT. Presently, it is unknown how improvements in emotion recognition develop during (VR-)SCT, which factors impact improvement, and how improvements in VR relate to improvement outside VR. Data were extracted from task logs from a pilot study and randomized controlled trials on VR-SCT (n = 55). Using mixed-effects generalized linear models, we examined the: (a) effect of treatment session (1-5) on VR accuracy and VR response time for correct answers; (b) main effects and moderation of participant and treatment characteristics on VR accuracy; and (c) the association between baseline performance on the Ekman 60 Faces task and accuracy in VR, and the interaction of Ekman 60 Faces change scores (i.e., post-treatment – baseline) with treatment session. Accounting for the task difficulty level and the type of presented emotion, participants became more accurate at the VR task (b = 0.20, p < 0.001) and faster (b = -0.10, p < 0.001) at providing correct answers as treatment sessions progressed. Overall emotion recognition accuracy in VR decreased with age (b = -0.34, p = 0.009); however, no significant interactions between any of the moderator variables and treatment session were found. An association between baseline Ekman 60 Faces and VR accuracy was found (b = 0.04, p = 0.006), but no significant interaction between difference scores and treatment session. Emotion recognition accuracy improved during VR-SCT, but improvements in VR may not generalize to non-VR tasks and daily life.

PMID:37071641 | DOI:10.1089/cyber.2022.0228