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Nevin Manimala Statistics

Plasma metabolome of healthy and Rhodococcus equi-infected foals over time

Equine Vet J. 2022 Oct 22. doi: 10.1111/evj.13894. Online ahead of print.

ABSTRACT

BACKGROUND: Foals that develop pulmonary ultrasonographic lesions on Rhodococcus equi (R. equi) endemic farms are treated with antibiotics because those at risk of developing clinical pneumonia (~20%) cannot be recognised early. Candidate biomarkers identified using metabolomics may aid targeted treatment strategies against R. equi.

OBJECTIVES: 1) To describe how foal ageing affects their plasma metabolome (birth to 8 weeks) and 2) To establish the effects that experimental infection with Rhodococcus equi (R. equi) has on foal metabolome.

STUDY DESIGN: Experimental study.

METHODS: Nine healthy newborn foals were experimentally infected with R. equi as described in a previous study. Foals were treated with oral antibiotics if they developed clinical pneumonia (n = 4, clinical group) or remained untreated if they showed no signs of disease (n = 5, subclinical group). A group of unchallenged foals (n = 4) was also included in the study. By the end of the study period (8 weeks), all foals were free of disease. This status was confirmed with transtracheal wash fluid evaluation and culture as well as thoracic ultrasonography. Plasma metabolomics was determined by GC-MS weekly for the study duration (8 weeks).

RESULTS: Foal’s plasma metabolome was altered by ageing (birth to 8 weeks) and experimental infection with R. equi as demonstrated using multivariate statistical analysis. The intensities of 25 and 28 metabolites were altered by ageing and infection (p < 0.05) respectively. Furthermore, 20 metabolites changed by more than 2-fold between clinical and subclinical groups.

MAIN LIMITATIONS: The number of foals is limited. Foals were experimentally infected with R. equi.

CONCLUSIONS: Ageing and R. equi infection induced changes in the plasma metabolome of foals. These results provide an initial description of foal’s plasma metabolome and serve as background for future identification of R. equi pneumonia biomarkers.

PMID:36273247 | DOI:10.1111/evj.13894

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Nevin Manimala Statistics

Automated clinical coding: what, why, and where we are?

NPJ Digit Med. 2022 Oct 22;5(1):159. doi: 10.1038/s41746-022-00705-7.

ABSTRACT

Clinical coding is the task of transforming medical information in a patient’s health records into structured codes so that they can be used for statistical analysis. This is a cognitive and time-consuming task that follows a standard process in order to achieve a high level of consistency. Clinical coding could potentially be supported by an automated system to improve the efficiency and accuracy of the process. We introduce the idea of automated clinical coding and summarise its challenges from the perspective of Artificial Intelligence (AI) and Natural Language Processing (NLP), based on the literature, our project experience over the past two and half years (late 2019-early 2022), and discussions with clinical coding experts in Scotland and the UK. Our research reveals the gaps between the current deep learning-based approach applied to clinical coding and the need for explainability and consistency in real-world practice. Knowledge-based methods that represent and reason the standard, explainable process of a task may need to be incorporated into deep learning-based methods for clinical coding. Automated clinical coding is a promising task for AI, despite the technical and organisational challenges. Coders are needed to be involved in the development process. There is much to achieve to develop and deploy an AI-based automated system to support coding in the next five years and beyond.

PMID:36273236 | DOI:10.1038/s41746-022-00705-7

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Nevin Manimala Statistics

The influence of a virtual reality entertainment program on depressive symptoms and sedentary behaviour in inpatient stroke survivors: a research protocol for a pilot randomized controlled trial

Pilot Feasibility Stud. 2022 Oct 22;8(1):230. doi: 10.1186/s40814-022-01189-8.

ABSTRACT

BACKGROUND: Sedentary behaviour among stroke inpatients may be due to high rates of depressive symptoms after stroke. Thus, efforts to address depressive symptoms among stroke inpatients are warranted to in turn lessen sedentary behaviour. Despite evidence that virtual reality (VR) is emerging as a method to help with depression, the use of VR to improve depression among inpatient stroke survivors has yet to be studied. In this paper, we report on the protocol investigating the feasibility of a VR entertainment system at improving depressive symptoms among stroke survivors receiving inpatient rehabilitation.

METHODS: In this single-blind randomized controlled trial, 30 inpatient stroke survivors from the rehabilitation unit at Kelowna General Hospital will be randomized to either (1) intervention: 3 times per week of VR entertainment for duration of inpatient rehabilitation or (2) control: usual care. Individuals will be included if they have a confirmed diagnosis of stroke, are 19 years of age or older, able to provide informed consent, have physician clearance to participate in the study (medically stable or fit), or are able to understand English. Outcome measures to address depressive symptoms (primary outcome), sedentary behaviour, motivation, anxiety, stress, and happiness (secondary outcome) will be administered at two timepoints: (1) baseline (T1) and (2) post-intervention (T2). Study analyses will consider study feasibility indicators and clinical (statistical) outcomes. Means and standard deviations (for continuous variables) and frequencies and proportions (for categorical variables) will be used to summarize the variables. Feasibility indicators will be dichotomized into either ‘success’ if they meet the a priori criteria, or ‘revise’ if they do not meet the criteria. Intervention effects post-intervention (T2) for the primary and secondary clinical outcomes will be estimated using linear regression including baseline (T1) controlling for age and sex.

DISCUSSION: The results of this trial will add to our understanding of depression and sedentary behaviour among individuals receiving inpatient stroke rehabilitation as well as the feasibility of a VR entertainment program to improve depressive symptoms, which will in turn may lessen sedentary behaviour in inpatient stroke survivors.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04011202 . First posted July 8, 2019 (study postponed from March 2020 to July 2021 due to COVID-19).

PMID:36273223 | DOI:10.1186/s40814-022-01189-8

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Nevin Manimala Statistics

Evaluating the impact of price regulation (Drug Price Control Order 2013) on antibiotic sales in India: a quasi-experimental analysis, 2008-2018

J Pharm Policy Pract. 2022 Oct 22;15(1):68. doi: 10.1186/s40545-022-00466-4.

ABSTRACT

BACKGROUND: In India, due to a lack of population-level financial risk protection mechanisms, the expenditure on healthcare is primarily out-of-pocket in nature. Through Drug Price Control Orders (DPCOs), the Indian Government attempts to keep medicine prices under check. The aim of this study was to measure the potential impact of DPCO 2013 on the utilization of antibiotics under price regulation in India using large nationally representative pharmaceutical sales data.

METHODS: We used interrupted time series analysis, a quasi-experimental research design to estimate the impact of DPCO 2013 on the utilization of antibiotics in the private sector in India. Indian pharmaceutical sales data set, PharmaTrac from a market research company-All Indian Origin Chemists and Distributors Limited-was used for the study. The data are collected from a panel of around 18,000 stockists across 23 different regions of the country. The primary outcome measure is the percentage change (increase or decrease) in the sales volume of the antibiotics under DPCO 2013, measured in standard units (SUs).

RESULTS: Our estimates suggest that post-intervention (after notification of DPCO 2013) there was an immediate reduction (level change) in the sales of antibiotics under DPCO 2013 by 3.7% (P > 0.05), followed by a sustained decline (trend change) of 0.3% (P > 0.05) as compared to the pre-intervention trend at the molecule level, but both changes were statistically insignificant. However, in terms of ‘average monthly market share,’ the DPCO 2013 notification resulted in a sharp reduction of 579% (P < 0.05) (level change) followed by a sustained increase of 9.5% (P > 0.05) (trend change) in the ‘market share of antibiotics under DPCO’ as compared to pre-intervention trend.

CONCLUSIONS: The impact of DPCO 2013 in terms of the overall increase in the utilization of antibiotics under price regulation was limited but there was a switch from non-price controlled antibiotics to price regulated antibiotics (notified under DPCO 2013). We argue that policies on price control need to be complemented with continuous monitoring of market behavior to have a measurable and long-term impact.

PMID:36273222 | DOI:10.1186/s40545-022-00466-4

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Adapting the self-assessment of contextual fit scale for implementation of evidence-based practices in adolescent HIV settings

Implement Sci Commun. 2022 Oct 22;3(1):115. doi: 10.1186/s43058-022-00349-4.

ABSTRACT

BACKGROUND: Contextual fit is an important variable in the implementation of evidence-based programs (EBPs). The objectives of the current study were to examine the psychometric properties of the adapted Self-Assessment of Contextual Fit (SACF) measure for HIV clinical care settings (calling it SACF-HIV) and explore how perceptions of contextual fit varied across two different interventions (an intervention to scale up tailored motivational interviewing and an individually focused HIV prevention intervention) and 12 clinical sites.

METHODS: We collected SACF-HIV data as part of a larger cross-project implementation science study (ATN 153). The study sample includes 128 clinicians, community health workers, interventionists, adherence counselors, and other members of the prevention and care team who engage in the implementation of EBPs at 12 HIV prevention and clinical care sites in the USA. We assessed the internal consistency of the SACF-HIV using Cronbach’s alpha and examined the sub-dimensionality of the scale with an exploratory factor analysis. To explore concurrent validity, we examined Pearson’s correlation coefficients between the adapted scale and fit-related sub-scale scores from the Evidence-Based Practice Attitudes Scale-50 (EBPAS-50). Variation in perceptions of fit by intervention was examined using descriptive statistics.

RESULTS: Internal consistency of the adapted scale was strong (α=0.895). Factor analyses revealed two sub-scales-one capturing general insights regarding contextual fit, such as perceptions of skill, experience, and alignment with client needs (loadings ranging from .5 to .84), and a second centering perceptions regarding implementation support, such as resources and administrative support (loadings ranging from .89 to .97). Concurrent validity was supported by statistically significant correlations in the expected direction with EBPAS-50 fit-related sub-scales (r=.33-.35, p ≤ 0.05). SACF-HIV mean fit scores varied by intervention and the difference was statistically significant (2.78 vs. 2.53, p < 0.05).

CONCLUSIONS: There are relatively few tools assessing perceptions of contextual fit in HIV clinical settings. These results suggest the 12-item adapted SACF is a reliable, valid global assessment of perceptions of contextual fit and implementation support. The SACF-HIV can be used by practitioners and researchers interested in understanding an implementation context when planning to prepare and support EBP implementation.

TRIAL REGISTRATION: TMI ClinicalTrials.gov NCT03681912; YMPH ClinicalTrials.gov NCT03488914.

PMID:36273221 | DOI:10.1186/s43058-022-00349-4

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Plasma proteome profiling identifies changes associated to AD but not to FTD

Acta Neuropathol Commun. 2022 Oct 22;10(1):148. doi: 10.1186/s40478-022-01458-w.

ABSTRACT

BACKGROUND: Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process.

METHODS: Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 ± 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 ± 7.9; 45% female), AD patients (n = 57; age = 65.5 ± 8.0; 39% female), and non-demented controls (n = 148; 61.3 ± 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 ± 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 ± 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 ± 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis.

RESULTS: Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified.

CONCLUSIONS: We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts.

PMID:36273219 | DOI:10.1186/s40478-022-01458-w

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A health promotion intervention to address youth violence among students in a technical college in Sri Lanka guided by the participatory action research approach: a study protocol

Res Involv Engagem. 2022 Oct 22;8(1):57. doi: 10.1186/s40900-022-00393-3.

ABSTRACT

BACKGROUND: Youth violence is a global public health issue and the highest rates are reported in Low and Middle-Income Countries (LMICs). Higher rates of youth violence are reported in Sri Lanka as well. Students who fail to continue higher studies in schools or enter the universities in Sri Lanka, enroll in technical colleges and are associated with a higher number of risk factors of violence. This study aims to empower youth (15-29 years old) of a technical college in Matale district, Sri Lanka, to carry out activities among themselves to improve their knowledge, change perceptions, and violence-related behaviours.

METHODS: The Participatory Action Research (PAR) approach will be used. The study participants will be eighty students in a technical college in Matale district, Sri Lanka. The study period will be three years. Study participants will also be collaborators and they will involve actively in all stages of the study. A health promotion intervention will be implemented to identify determinants of youth violence and to design and implement actions while monitoring the changes. The data will be collected mainly through focus group discussions and key informant interviews both before and after the health promotion intervention. Additionally, a self-administered questionnaire will be used and the principal investigator will maintain a reflective diary. The qualitative data will be analysed thematically whereas quantitative data will be analysed using descriptive statistics. Data will be triangulated to increase the rigour of the study.

DISCUSSION: According to literature, PAR is not widely used in health promotion. The enabling and empowerment goals of health promotion are fulfilled in PAR. Thus, this will be a novel experience for researchers and this will stimulate discussion on the combination of PAR and health promotion. This study design itself promotes active participant involvement and it may generate effective youth-led, culturally appropriate actions to address youth violence. The findings will describe what works and why it works and will help Sri Lanka and similar LMICs to create safe environments for youth in educational institutes or training colleges.

PMID:36273215 | DOI:10.1186/s40900-022-00393-3

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Feasibility of point of care testing for prevention and management of breast cancer therapy associated comorbidities in 6 African countries: short communication

BMC Res Notes. 2022 Oct 22;15(1):328. doi: 10.1186/s13104-022-06204-y.

ABSTRACT

OBJECTIVE: Obesity and mediators of inflammation have been identified as the most important risk and predictive factors in postmenopausal breast cancer (BC) survivors using aromatase inhibitors (AIs). This study was conducted to assess the impact of point of care technology (PCOT) as part of pathology supported genetic testing (PSGT) to prevent BC therapy-associated comorbidities in African settings.

RESULTS: The study revealed that high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) are predictors of cardiovascular (CVD) related adverse events in obese postmenopausal patients subjected to AIs. There were statistically significant variations in total body fat (TBF), weight, hs-CRP, body mass index (BMI), homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. The above inflammatory markers can be incorporated in pathology supported genetic testing (PSGT) using HyBeacon® probe technology at POC for prediction and management of AI-associated adverse events among postmenopausal breast cancer survivors and associated comorbidities. The barriers for implementation of POCT application among six African countries for diagnosis of breast cancer were documented as insufficient of BC diagnosis and management capacity at different levels of health system.

PMID:36273209 | DOI:10.1186/s13104-022-06204-y

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Patient and public involvement in an international rheumatology translational research project: an evaluation

BMC Rheumatol. 2022 Oct 22;6(1):83. doi: 10.1186/s41927-022-00311-w.

ABSTRACT

BACKGROUND: Rheuma Tolerance for Cure (RTCure) is a five-year international collaboration between academia, industry and patients/members of the public. It focuses on developing approaches to predict the onset of rheumatoid arthritis (RA) and designing clinical trials to reduce the risk of disease development through immune-tolerising and other treatments. We conducted a mid-term evaluation of patient and public involvement (PPI) within the project.

METHODS: Two surveys on PPI were co-designed by the PPI Coordinator, Patient/Public Research Partners (PRPs) and a researcher. Both anonymous, electronic surveys were distributed to 61 researchers and 9 PRPs. Quantitative survey data were analysed using descriptive statistics and free text responses underwent inductive thematic analysis.

RESULTS: Researcher and Patient response rates were 33% and 78%, respectively. Quantitative Researcher Survey data highlighted that (i) responding researchers represented all seven Work Packages (WPs), (ii) 40% thought PRPs had made a large or extremely large contribution to their own WPs, (iii) 55% thought PPI has had a moderate or large impact on RTCure, (iv) 75% worked with PRPs in RTCure, and (v) 60% said PRPs had affected their research thinking. Quantitative PRP Survey data highlighted that (i) PRPs were most involved in four WPs, (ii) 43% thought they had made a minor contribution to their main WP, (iii) 57% thought PPI has had a small impact on RTCure, and (iv) 57% thought they received too little feedback on the outcome of their contribution to different tasks. Four main themes were identified in both surveys: ‘PRP contributions’, ‘Experiences of PPI’, ‘Impact of PPI on RTCure’, and ‘How PPI can be improved’. Two additional themes from the Researcher Survey were ‘Impact of PPI on researchers’ and ‘Influence on Future Projects’, and from the PRP Survey were ‘Impact of PPI on PRPs’ and ‘Engagement with PRPs’.

CONCLUSION: PPI seemed to have a significant impact on RTCure, however, PRPs were less aware. A focus on improving communication between PRPs and researchers (facilitated by the PPI Coordinator), and providing PPI training for researchers is likely to improve involvement. Complex legal agreements for PRPs should be avoided and careful attention paid to appropriate PRP compensation.

PMID:36273206 | DOI:10.1186/s41927-022-00311-w

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Layer-specific, retinotopically-diffuse modulation in human visual cortex in response to viewing emotionally expressive faces

Nat Commun. 2022 Oct 22;13(1):6302. doi: 10.1038/s41467-022-33580-7.

ABSTRACT

Viewing faces that are perceived as emotionally expressive evokes enhanced neural responses in multiple brain regions, a phenomenon thought to depend critically on the amygdala. This emotion-related modulation is evident even in primary visual cortex (V1), providing a potential neural substrate by which emotionally salient stimuli can affect perception. How does emotional valence information, computed in the amygdala, reach V1? Here we use high-resolution functional MRI to investigate the layer profile and retinotopic distribution of neural activity specific to emotional facial expressions. Across three experiments, human participants viewed centrally presented face stimuli varying in emotional expression and performed a gender judgment task. We found that facial valence sensitivity was evident only in superficial cortical layers and was not restricted to the retinotopic location of the stimuli, consistent with diffuse feedback-like projections from the amygdala. Together, our results provide a feedback mechanism by which the amygdala directly modulates activity at the earliest stage of visual processing.

PMID:36273204 | DOI:10.1038/s41467-022-33580-7