Leveraging qualitative approaches to guide sustainable international research collaborations

Qualitative research approaches were used to launch an international research collaboration between the U. S. and Cambodia. Cambodian officials requested assistance in learning qualitative approaches to complement the research skills of Cambodian mental health providers. This article provides a description of how U. S. researchers responded to that request and engaged with Cambodian psychiatrists to explore mental health needs and interventions in both countries and initiate a sustainable relationship. The early focus on qualitative research methodologies may be an avenue that mitigates some of the challenges that can characterize international research. In this study, early communications involved developing a plan to teach qualitative methods while also collecting and analyzing data in both countries that would address the mental health concerns experienced by respective care providers. A case study exemplar was embedded with a scripted focus group guide to collect data from U. S. focus groups, then share with Cambodian psychiatrists. Components of hermeneutic phenomenological interviewing and descriptive content analysis were used to simultaneously teach and enact the research methods, gather data in both countries to analyze, and inspire participants to replicate the methods in their ongoing work. Cambodian psychiatrists were able to demonstrate competence in facilitating focus groups after being participant-observers. Researcher/practitioners from both U. S. and Cambodian teams gained new understandings about the mental health needs of their patients. The mutual engagement of a research focus is an effective way to establish cross-cultural relationships. The challenges of staying with stable teams over times remain, but the content shared and learned in a participatory structure yields understandings that cross cultural boundaries. Anticipated and unexpected challenges may be offset by an intention of reciprocity and mutual engagement. The use of qualitative methodologies, early and repeatedly, can facilitate relational understanding

Protocol for a randomized controlled trial in Cambodian individuals with PTSD: Trauma-Informed Treatment Algorithms for Advancing Novel Outcomes (project TITAN)

Low- and middle-income countries shoulder a disproportionate burden of mental health disorders with limited resources to support the provision of care using culturally relevant, evidence-based interventions. This is particularly true in Cambodia where the population continues to confront traumatic consequences of the Khmer Rouge genocide that targeted educated people, including treatment providers. Trauma-Informed Treatment Algorithms for Advancing Novel Outcomes (Project TITAN) will examine proof of concept and preliminary efficacy of culturally tailored interventions for symptoms of post-traumatic stress (PTS) among Cambodian adults. A stepped care randomized controlled trial enrolling people seeking mental health treatment and priority populations with high rates of trauma exposure, including female entertainment and sex workers and sexual and gender minorities. In total, 160 participants with symptoms of PTS are randomized to Stabilization Techniques or Behavioral Activation plus Stabilization Techniques, implemented within a culturally relevant framework. Individuals who do not demonstrate a reduction in symptoms of PTS after six treatment sessions receive Eye Movement Desensitization and Reprocessing therapy. PTS, depression, anxiety, and substance use are assessed at baseline and two and four months post-randomization. The percentage of individuals achieving reductions in symptoms of PTS after four months is the primary outcome. Secondary outcomes are depression, anxiety, and substance use over four months. Finally, machine learning analyses will be conducted to identify features at baseline and during treatment that predict outcomes. Findings will guide future development and implementation of interventions to improve mental health conditions among individuals in Cambodia and other resource-limited settings

Cognitive Phenotypes of HIV Defined Using a Novel Data-driven Approach

The current study applied data-driven methods to identify and explain novel cognitive phenotypes of HIV. Methods: 388 people with HIV (PWH) with an average age of 46 (15.8) and median plasma CD4+ T-cell count of 555 copies/mL (79% virally suppressed) underwent cognitive testing and 3T neuroimaging. Demographics, HIV disease variables, and health comorbidities were recorded within three months of cognitive testing/neuroimaging. Hierarchical clustering was employed to identify cognitive phenotypes followed by ensemble machine learning to delineate the features that determined membership in the cognitive phenotypes. Hierarchical clustering identified five cognitive phenotypes. Cluster 1 (n=97) was comprised of individuals with normative performance on all cognitive tests. The remaining clusters were defined by impairment on action fluency (Cluster 2; n=46); verbal learning/memory (Cluster 3; n=73); action fluency and verbal learning/memory (Cluster 4; n=56); and action fluency, verbal learning/memory, and tests of executive function (Cluster 5; n=114). HIV detectability was most common in Cluster 5. Machine learning revealed that polysubstance use, race, educational attainment, and volumes of the precuneus, cingulate, nucleus accumbens, and thalamus differentiated membership in the normal vs. impaired clusters. The determinants of persistent cognitive impairment among PWH receiving suppressive treatment are multifactorial nature. Viral replication after ART plays a role in the causal pathway, but psychosocial factors (race inequities, substance use) merit increased attention as critical determinants of cognitive impairment in the context of ART. Results underscore the need for comprehensive person-centered interventions that go beyond adherence to patient care to achieve optimal cognitive health among PWH

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status