Nevin Manimala

Blood. 2021 Mar 3:blood.2020009362. doi: 10.1182/blood.2020009362. Online ahead of print.

ABSTRACT

Prior studies suggest increased CMV infection following haploidentical donor transplantation with post-transplant cyclophosphamide (HaploCy). The role of allograft source and PTCy in CMV infection and disease is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection as well as transplant outcomes as it relates to CMV serostatus and occurrence of CMV infection by d180. We examined patients reported to CIBMTR between 2012-2017 who had received HaploCy (n = 757), Sib with PTCy (SibCy, n=403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n=1605) for AML/ALL/MDS. Cumulative incidences of CMV infection by d180 were 42% (99% CI, 37-46), 37% (31 – 43), and 23% (20 – 26), respectively [p<0.001]. CMV end-organ disease was statistically comparable. CMV infection risk was highest for CMV-Seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor [HaploCy (n=545): HR 50.3 (14.4 – 175.2); SibCy (n=279): HR 47.7 (13.3 – 171.4); SibCNI (n=1065): HR 24.4 (7.2 – 83.1); p<0.001]. D+/R- patients also had increased risk for CMV infection. Among seropositive recipients or those developing CMV infection, HaploCy had worse OS and NRM. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic GVHD overall, but CMV infection in PTCy recipients was associated with higher cGVHD (p=0.006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally CMV infection may negate the cGVHD protection of PTCy. This study supports aggressive prevention strategies in all patients receiving PTCy.

PMID:33657221 | DOI:10.1182/blood.2020009362

J Am Med Inform Assoc. 2021 Feb 28:ocab001. doi: 10.1093/jamia/ocab001. Online ahead of print.

ABSTRACT

OBJECTIVE: Providing behavioral health interventions via smartphones allows these interventions to be adapted to the changing behavior, preferences, and needs of individuals. This can be achieved through reinforcement learning (RL), a sub-area of machine learning. However, many challenges could affect the effectiveness of these algorithms in the real world. We provide guidelines for decision-making.

MATERIALS AND METHODS: Using thematic analysis, we describe challenges, considerations, and solutions for algorithm design decisions in a collaboration between health services researchers, clinicians, and data scientists. We use the design process of an RL algorithm for a mobile health study “DIAMANTE” for increasing physical activity in underserved patients with diabetes and depression. Over the 1.5-year project, we kept track of the research process using collaborative cloud Google Documents, Whatsapp messenger, and video teleconferencing. We discussed, categorized, and coded critical challenges. We grouped challenges to create thematic topic process domains.

RESULTS: Nine challenges emerged, which we divided into 3 major themes: 1. Choosing the model for decision-making, including appropriate contextual and reward variables; 2. Data handling/collection, such as how to deal with missing or incorrect data in real-time; 3. Weighing the algorithm performance vs effectiveness/implementation in real-world settings.

CONCLUSION: The creation of effective behavioral health interventions does not depend only on final algorithm performance. Many decisions in the real world are necessary to formulate the design of problem parameters to which an algorithm is applied. Researchers must document and evaulate these considerations and decisions before and during the intervention period, to increase transparency, accountability, and reproducibility.

TRIAL REGISTRATION: clinicaltrials.gov, NCT03490253.

PMID:33657217 | DOI:10.1093/jamia/ocab001

PLoS One. 2021 Mar 3;16(3):e0247788. doi: 10.1371/journal.pone.0247788. eCollection 2021.

ABSTRACT

The importance given to minimising health issues and promoting natural behaviours is a polarising issue within farm animal welfare. It is predominantly thought that members of the public prioritise animals being able to behave naturally over other aspects of farm animal welfare, such as addressing health issues. However, public perspectives may be more multi-dimensional than is generally thought, with the importance given to these different elements of welfare dependent on the situation and state of the animals in question. To examine this, a factorial survey using vignettes, which experimentally manipulated the different levels of health (high health vs. low health) and natural behaviour provision (high behaviour vs. low behaviour), was completed by a sample (n = 810) representative of the UK population (on age, gender, ethnicity). Contrary to the predominant view, this study found animal health had the greatest effect on participants’ judgements, explaining more of the variance in their assessments of animal welfare than any other factor. However, findings also indicated that participants considered animal welfare to be most positive when both health issues are minimised and natural behaviours are promoted. Attitudes to natural behaviours also varied more between participants, with females, individuals who do not (regularly) eat meat and those with a greater belief in animal mind giving greater priority to natural behaviours. In the context of public and private welfare standards seeking to meet public expectations, this study provides important insights into how public perspectives of animal welfare are more nuanced than previously thought, influenced by the context of the animal, the aspect of welfare in question and personal characteristics.

PMID:33657189 | DOI:10.1371/journal.pone.0247788

PLoS One. 2021 Mar 3;16(3):e0247995. doi: 10.1371/journal.pone.0247995. eCollection 2021.

ABSTRACT

BACKGROUND: Primary care is the major point of access in most health systems in developed countries and therefore for the detection of coronavirus disease 2019 (COVID-19) cases. The quality of its IT systems, together with access to the results of mass screening with Polymerase chain reaction (PCR) tests, makes it possible to analyse the impact of various concurrent factors on the likelihood of contracting the disease.

METHODS AND FINDINGS: Through data mining techniques with the sociodemographic and clinical variables recorded in patient’s medical histories, a decision tree-based logistic regression model has been proposed which analyses the significance of demographic and clinical variables in the probability of having a positive PCR in a sample of 7,314 individuals treated in the Primary Care service of the public health system of Catalonia. The statistical approach to decision tree modelling allows 66.2% of diagnoses of infection by COVID-19 to be classified with a sensitivity of 64.3% and a specificity of 62.5%, with prior contact with a positive case being the primary predictor variable.

CONCLUSIONS: The use of a classification tree model may be useful in screening for COVID-19 infection. Contact detection is the most reliable variable for detecting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. The model would support that, beyond a symptomatic diagnosis, the best way to detect cases would be to engage in contact tracing.

PMID:33657164 | DOI:10.1371/journal.pone.0247995

PLoS One. 2021 Mar 3;16(3):e0247787. doi: 10.1371/journal.pone.0247787. eCollection 2021.

ABSTRACT

Elucidating the genetic variation and structure of Lemnos and Lesvos sheep is critical for maintaining local genetic diversity, ecosystem integrity and resilience of local food production of the two North Aegean islands. In the present study, we explored genetic diversity and differentiation as well as population structure of the Lemnos and Lesvos sheep. Furthermore, we sought to identify a small panel of markers with the highest discriminatory power to assign animals across islands. A total number of n = 424 (n = 307, Lemnos and n = 117, Lesvos) ewes, sampled from n = 24 herds dispersed at different geographic regions on the two islands, were genotyped with the 50K SNP array. Mean observed heterozygosity was higher (but not statistically significantly different) in Lesvos than in Lemnos population (0.384 vs. 0.377) while inbreeding levels were higher in Lemnos than Lesvos herds (0.065 vs. 0.031). Results of principal components along with that of admixture analysis and estimated genetic distances revealed genetic clusters corresponding to Lesvos and Lemnos origin and the existence of infrastructure within islands that were associated with geographical isolation and genetic history of the studied populations. In particular, genetic analyses highlighted three geographically isolated herds in Lemnos that are located at mountainous areas of the island and are characterized as representatives of the local sheep by historic data and reports. Admixture analysis also showed a shared genetic background between Lemnos and Lesvos sheep attributable to past gene flow. Little overall genetic differentiation was detected between the two island sheep populations, while 150 discriminatory SNPs could accurately assign animals to their origin. Present results are comparable with those reported in the worldwide sheep breeds, suggesting geography related genetic patterns across and within islands and the existence of the local Lemnos sheep.

PMID:33657161 | DOI:10.1371/journal.pone.0247787

PLoS One. 2021 Mar 3;16(3):e0247296. doi: 10.1371/journal.pone.0247296. eCollection 2021.

ABSTRACT

Frailty is considered to be a complex concept based mainly on physical vulnerability, but also vulnerabilities in mental/psychological and social aspects. Frailty can be reversible with appropriate intervention; however, factors that are important in recovering from frailty have not been clarified. The aim of the present study was to identify factors that help an individual reverse frailty progression and characteristics of individuals that have recovered from frailty. Community-dwelling people aged ≥75 years who responded to the Kihon Checklist (KCL) were enrolled in the study. The KCL consists of 25 yes/no questions in 7 areas: daily-life related activities, motor functions, nutritional status, oral functions, homebound, cognitive functions, and depressed mood. The number of social activities, degree of trust in the community, degree of interaction with neighbors, and subjective age were also evaluated. Frailty was assessed based on the number of checked items: 0-3 for robust, 4-7 for pre-frailty, and ≥8 for frailty. A total of 5050 participants were included for statistical analysis. At the time of the baseline survey in 2016, 18.7% (n = 942) of respondents had frailty, and the follow-up survey showed that the recovery rate from frailty within 2 years (median 24 months) was 31.8% (n = 300). Multiple logistic regression analysis showed that exercise-based social participation (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.2-3.4; P<0.01) and self-rated health (OR 1.2, CI 1.0-1.5; P = 0.02) were related to reversing frailty progression. Principal component analysis indicated that the main factors constituting the first principal component (contribution rate, 18.3%) included items related to social capital, such as interaction with neighbors, trust in the community, and number of social participation activities. Our results demonstrate that exercise-based social participation and high self-rated health have associations with reversing frailty progression. Individuals that recovered from frailty are characterized by high individual-level social capital components (i.e., trust in community, interaction with neighbors, and social participation).

PMID:33657160 | DOI:10.1371/journal.pone.0247296

PLoS One. 2021 Mar 3;16(3):e0247251. doi: 10.1371/journal.pone.0247251. eCollection 2021.

ABSTRACT

In the context of COVID-19 pandemic, we aimed to analyze the epidemiology, clinical characteristics, risk factors for mortality and impact of COVID-19 on outcomes of solid organ transplant (SOT) recipients compared to a cohort of non transplant patients, evaluating if transplantation could be considered a risk factor for mortality. From March to May 2020, 261 hospitalized patients with COVID-19 pneumonia were evaluated, including 41 SOT recipients. Of these, thirty-two were kidney recipients, 4 liver, 3 heart and 2 combined kidney-liver transplants. Median time from transplantation to COVID-19 diagnosis was 6 years. Thirteen SOT recipients (32%) required Intensive Care Unit (ICU) admission and 5 patients died (12%). Using a propensity score match analysis, we found no significant differences between SOT recipients and non-transplant patients. Older age (OR 1.142; 95% [CI 1.08-1.197]) higher levels of C-reactive protein (OR 3.068; 95% [CI 1.22-7.71]) and levels of serum creatinine on admission (OR 3.048 95% [CI 1.22-7.57]) were associated with higher mortality. The clinical outcomes of SARS-CoV-2 infection in our cohort of SOT recipients appear to be similar to that observed in the non-transplant population. Older age, higher levels of C-reactive protein and serum creatinine were associated with higher mortality, whereas SOT was not associated with worse outcomes.

PMID:33657157 | DOI:10.1371/journal.pone.0247251

PLoS One. 2021 Mar 3;16(3):e0247259. doi: 10.1371/journal.pone.0247259. eCollection 2021.

ABSTRACT

INTRODUCTION: Empathy is essential for high quality health care. Health care disparities may reflect a systemic lack of empathy for disadvantaged people; however, few data exist on disparities in patient experience of empathy during face-to-face health care encounters with individual clinicians. We systematically analyzed the literature to test if socioeconomic status (SES) and race/ethnicity disparities exist in patient-reported experience of clinician empathy.

METHODS: Using a published protocol, we searched Ovid MEDLINE, PubMed, CINAHL, EMBASE, CENTRAL and PsychINFO for studies using the Consultation and Relational Empathy (CARE) Measure, which to date is the most commonly used and well-validated methodology for measuring clinician empathy from the patient perspective. We included studies containing CARE Measure data stratified by SES and/or race/ethnicity. We contacted authors to request stratified data, when necessary. We performed quantitative meta-analyses using random effects models to test for empathy differences by SES and race/ethnicity.

RESULTS: Eighteen studies (n = 9,708 patients) were included. We found that, compared to patients whose SES was not low, low SES patients experienced lower empathy from clinicians (mean difference = -0.87 [95% confidence interval -1.72 to -0.02]). Compared to white patients, empathy scores were numerically lower for patients of multiple race/ethnicity groups (Black/African American, Asian, Native American, and all non-whites combined) but none of these differences reached statistical significance.

CONCLUSION: These data suggest an empathy gap may exist for patients with low SES. More research is needed to further test for SES and race/ethnicity disparities in clinician empathy and help promote health care equity.

TRIAL REGISTRATION: Registration (PROSPERO): CRD42019142809.

PMID:33657153 | DOI:10.1371/journal.pone.0247259

PLoS One. 2021 Mar 3;16(3):e0246691. doi: 10.1371/journal.pone.0246691. eCollection 2021.

ABSTRACT

AIM: Real-world predictors of major bleeding (MB) have been well-studied among warfarin users, but not among all direct oral anticoagulant (DOAC) users diagnosed with atrial fibrillation (AF). Thus, our goal was to build a predictive model of MB for new users of all oral anticoagulants (OAC) with AF.

METHODS: We identified patients hospitalized for any cause and discharged alive in the community from 2011 to 2017 with a primary or secondary diagnosis of AF in Quebec’s RAMQ and Med-Echo administrative databases. Cohort entry occurred at the first OAC claim. Patients were categorized according to OAC type. Outcomes were incident MB, gastrointestinal bleeding (GIB), non-GI extracranial bleeding (NGIB) and intracranial bleeding within 1 year of follow-up. Covariates included age, sex, co-morbidities (within 3 years before cohort entry) and medication use (within 2 weeks before cohort entry). We used logistic-LASSO and adaptive logistic-LASSO regressions to identify MB predictors among OAC users. Discrimination and calibration were assessed for each model and a global model was selected. Subgroup analyses were performed for MB subtypes and OAC types.

RESULTS: Our cohort consisted of 14,741 warfarin, 3,722 dabigatran, 6,722 rivaroxaban and 11,196 apixaban users aged 70-86 years old. The important MB predictors were age, prior MB and liver disease with ORs ranging from 1.37-1.64. The final model had a c-statistic of 0.63 (95% CI 0.60-0.65) with adequate calibration. The GIB and NGIB models had similar c-statistics of 0.65 (95% CI 0.63-0.66) and 0.67 (95% CI 0.64-0.70), respectively.

CONCLUSIONS: MB and MB subtype predictors were similar among DOAC and warfarin users. The predictors selected by our models and their discriminative potential are concordant with published data. Thus, these models can be useful tools for future pharmacoepidemiologic studies involving older oral anticoagulant users with AF.

PMID:33657116 | DOI:10.1371/journal.pone.0246691

PLoS Med. 2021 Mar 3;18(3):e1003415. doi: 10.1371/journal.pmed.1003415. eCollection 2021 Mar.

ABSTRACT

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression.

METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion.

CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration.

TRIAL REGISTRATION: NCT04375098.

PMID:33657114 | DOI:10.1371/journal.pmed.1003415