Clinical Utility of the Molecular Microscope Diagnostic System in a Real-World Transplant Cohort: Moving Towards a New Paradigm.

Objectives: To evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx ) of biopsy specimens in heart transplant (HT ) recipients with suspected rejection. Introduction: Histopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of "biopsy-negative" rejection has raised concerns about the likelihood of false-negative results. MMDx, which uses gene expression to detect early signs of rejection, is a promising test to further refine the assessment of HT rejection. Methods: Single-center prospective study of 418 consecutive for-cause endomyocardial biopsies performed between November 2022 and May 2024. Each biopsy was graded based on histology and assessed for rejection patterns using MMDx. MMDx results were deemed positive if borderline or definitive rejection was present. The impact of MMDx results on clinical management was evaluated. Primary outcomes were 1-year survival and graft dysfunction following MMDx-guided clinical management. Secondary outcomes included changes in donor-specific antibodies, MMDx gene transcripts, and donor-derived cell-free DNA (dd-cfDNA) levels. Results: We analyzed 418 molecular samples from 237 unique patients. Histology identified rejection in 32 cases (7.7%), while MMDx identified rejection in 95 cases (22.7%). Notably, in 79 of the 95 cases where MMDx identified rejection, histology results were negative, with the majority of these cases being antibody-mediated rejection (62.1%). Samples with rejection on MMDx were more likely to show a combined elevation of dd-cfDNA and peripheral blood gene expression profiling than those with borderline or negative MMDx results (36.7% vs 28.0% vs 10.3%; p<0.001). MMDx results led to the implementation of specific antirejection protocols or changes in immunosuppression in 20.4% of cases, and in 73.4% of cases where histology was negative and MMDx showed rejection. 1-year survival was better in the positive MMDx group where clinical management was guided by MMDx results (87.0% vs 78.6%; log rank p=0.0017). Conclusions: In our cohort, MMDx results more frequently indicated rejection than histology, often leading to the initiation of antirejection treatment. Intervention guided by positive MMDx results was associated with improved outcomes.

Comparative Analysis of Ischemia-Reperfusion Injury in Heart Transplantation: A Single-Center Study Evaluating Conventional Ice-Cold Storage versus the Paragonix SherpaPak Cardiac Transport System.

BACKGROUND: Since the 2018 allocation system change in heart transplantation (HT), ischemic times have increased, which may be associated with peri-operative and post-operative complications. This study aimed to compare ischemia reperfusion injury (IRI) in hearts preserved using ice-cold storage (ICS) and the Paragonix SherpaPak TM Cardiac Transport System (CTS). METHODS: From January 2021 to June 2022, consecutive endomyocardial biopsies from 90 HT recipients were analyzed by a cardiac pathologist in a single-blinded manner: 33 ICS and 57 CTS. Endomyocardial biopsies were performed at three-time intervals post-HT, and the severity of IRI manifesting histologically as coagulative myocyte necrosis (CMN) was evaluated, along with graft rejection and graft function. RESULTS: The incidence of IRI at weeks 1, 4, and 8 post-HT were similar between the ICS and CTS groups. There was a 59.3% statistically significant reduction in CMN from week 1 to 4 with CTS, but not with ICS. By week 8, there were significant reductions in CMN in both groups. Only 1 out of 33 (3%) patients in the ICS group had an ischemic time >240 mins, compared to 10 out of 52 (19%) patients in the CTS group. During the follow-up period of 8 weeks to 12 months, there were no significant differences in rejection rates, formation of de novo donor-specific antibodies and overall survival between the groups. CONCLUSION: The CTS preservation system had similar rates of IRI and clinical outcomes compared to ICS despite longer overall ischemic times. There is significantly more recovery of IRI in the early post operative period with CTS. This study supports CTS as a viable option for preservation from remote locations, expanding the donor pool.

Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis.

We present a gene-level regulatory model, single-cell ATAC + RNA linking (SCARlink), which predicts single-cell gene expression and links enhancers to target genes using multi-ome (scRNA-seq and scATAC-seq co-assay) sequencing data. The approach uses regularized Poisson regression on tile-level accessibility data to jointly model all regulatory effects at a gene locus, avoiding the limitations of pairwise gene-peak correlations and dependence on peak calling. SCARlink outperformed existing gene scoring methods for imputing gene expression from chromatin accessibility across high-coverage multi-ome datasets while giving comparable to improved performance on low-coverage datasets. Shapley value analysis on trained models identified cell-type-specific gene enhancers that are validated by promoter capture Hi-C and are 11× to 15× and 5× to 12× enriched in fine-mapped eQTLs and fine-mapped genome-wide association study (GWAS) variants, respectively. We further show that SCARlink-predicted and observed gene expression vectors provide a robust way to compute a chromatin potential vector field to enable developmental trajectory analysis.

Community-Driven Prioritization of Primary Health Care Access Issues by Bangladeshi-Canadians to Guide Program of Research and Practice.

Research around probable solutions to immigrants accessing health care in Canada is not extensive, and the perspective of immigrant communities on priorities and potential solutions has not been captured effectively. The purpose of this article is to describe a research initiative that involved grassroots community members as producers of research priorities on primary care access issues. This study aimed to seek input from an immigrant community in Calgary, Canada. Members of the Bangladeshi community of Calgary were asked through a survey to rank 10 predefined primary care access topics as to what they felt constituted priorities for solution-oriented research (1, highest; 10, lowest). We used frequencies and percentages to describe the participant demographics. Ratings of preferred research themes were analyzed on the basis of relative weighted priority rank. We received 432 responses: 51.2% female; 58.9% aged 36 to 55 years; 90.5% had university-level education; 46.2% immigrated to Canada between 10 and 19 years ago; 82.5% employed full/part-time or self-employed. Lack of resources, lack of knowledge, health care cost, and workplace-related barriers were among the top-ranked topics identified as solution-oriented research priorities. Through partnerships and reciprocal learning, public input can increase insider perspectives to help develop interventions that align with the needs of community members.

Overcoming the Challenges Faced by Immigrant Populations While Accessing Primary Care: Potential Solution-oriented Actions Advocated by the Bangladeshi-Canadian Community.

INTRODUCTION: Immigrants continue to face significant challenges in accessing primary healthcare (PHC) that often negatively impact their health. The present research aims to capture the perspectives of immigrants to identify potential approaches to enhance PHC access for this group. METHODS: Focus group discussions (FGDs) were conducted among a sample of first-generation Bangladeshi immigrants who had experience with PHC in Canada. A total of 13 FGDs (7 among women, 6 among men) were conducted with 80 participants (women = 42, men = 38) in their preferred language, Bangla. We collected demographic information prior to each focus group and used descriptive statistics to identify the socio-demographic characteristics of participants. We applied thematic analysis to examine qualitative data to generate a list of themes of possible approaches to improve PHC access. RESULTS: The focus group findings identified different levels of approaches to improve PHC access: individual-, community-, service provider-, and policy-level. Individual-level approaches included increased self-awareness of health and wellness and personal knowledge of cultural differences in healthcare services and improved communication skills. At the community level, supports for community members to access care included health education workshops, information sessions, and different support programs (eg, carpool services for senior members). Suggested service-level approaches included providers taking necessary steps to ensure an effective doctor-patient relationship with immigrants (eg, strategies to promote cultural competencies, hiring multicultural staff). FGD participants also raised the importance of government- or policy-level solutions to ensure high quality of care (eg, increased after-hour clinics and lab/diagnostic services). CONCLUSIONS: Although barriers to immigrants accessing healthcare are well documented in the literature, solutions to address them are under-researched. To improve healthcare access, physicians, community health centers, local health agencies, and public health units should collaborate with members of immigrant communities to identify appropriate interventions.

Perceived Challenges and Unmet Primary Care Access Needs among Bangladeshi Immigrant Women in Canada.

INTRODUCTION: Understanding barriers in primary health care access faced by Canadian immigrants, especially among women, is important for developing mitigation strategies. The aim of this study was to gain an in-depth understanding of perceived challenges and unmet primary health care access needs of Bangladeshi immigrant women in Canada. METHODS: In this qualitative study, we conducted 7 focus groups among a sample of 42 first-generation immigrant women on their experiences in primary health care access in their preferred language, Bangla. Descriptive analysis was used for their socio-demographic characteristics and inductive thematic analysis was applied to the qualitative data. RESULTS: The hurdles reported included long wait time at emergency service points, frustration from slow treatment process, economic losses resulting from absence at work, communication gap between physicians and immigrant patients, and transportation problem to go to the health care centers. No access to medical records for walk-in doctors, lack of urgent care, and lack of knowledge about Canadian health care systems are a few of other barriers emerged from the focus group discussions. CONCLUSIONS: The community perception about lack of primary health care resources is quite prevalent and is considered as one of the most important barriers by the grassroots community members.

Perceived barriers and primary care access experiences among immigrant Bangladeshi men in Canada.

OBJECTIVE: The study aimed to explore the experience of male members of a rapidly grown community of Bangladeshi immigrants while accessing primary healthcare (PHC) services in Canada. DESIGN: A qualitative research was conducted among a sample of Bangladeshi immigrant men through a community-based participatory research approach. Focus group discussions were conducted to collect the qualitative data where thematic analysis was applied. SETTING: The focus group discussions were held in various community centres such as individual meeting rooms at public libraries, community halls and so on arranged in collaboration with community organisations while ensuring complete privacy. PARTICIPANT: Thirty-eight adults, Bangladeshi immigrant men, living in Calgary were selected for this study and participated in six different focus groups. The sample represents mostly married, educated, Muslim, Bangla speaking, aged over 25 years, full-time or self-employed and living in an urban centre in Canada >5 years. RESULT: The focus groups have highlighted long wait time as an important barrier. Long wait at the emergency room, difficulties to get access to general physicians when feeling sick, slow referral process and long wait at the clinic even after making an appointment impact their daily chores, work and access to care. Language is another important barrier that impedes effective communication between physicians and immigrant patients, thus the quality of care. Unfamiliarity with the healthcare system and lack of resources were also voiced that hinder access to healthcare for immigrant Bangladeshi men in Canada. However, no gender-specific barriers unique to men have been identified in this study. CONCLUSION: The barriers to accessing PHC services for Bangladeshi immigrant men are similar to that of other visible minority immigrants. It is important to recognise the extent of barriers across various immigrant groups to effectively shape public policy and improve access to PHC.

Cost-Benefit Analysis of a Chlamydia trachomatis Vaccine Program in Adolescent Girls in the United States.

BACKGROUND: With >1.4 million cases in the United States reported to the Centers for Disease Control and Prevention in 2012, Chlamydia trachomatis infection is a major public health concern. We examined the impact of a C trachomatis vaccination program using a decision-analysis model to estimate the effects of vaccination on C trachomatis-associated costs and morbidity. METHODS: We developed a Markov model considering a cohort of 2158117 US females aged 9 to 26 years. Morbidity, death, and healthcare-associated costs associated with chlamydial infection of mothers and fetuses/neonates were calculated over a 17-year time frame. We developed 2 major comparison arms, namely, a C trachomatis vaccination program and no C trachomatis vaccination program. Base-case efficacy and coverage were set to those of human papillomavirus in the United States with all variables, including efficacy and coverage, ranged in sensitivity analyses. RESULTS: On the basis of a base-case analysis, a vaccination program would cost an estimated $710 million for a cohort of 2158117 women over a 17-year period, an increase of $41 million over having no vaccination program. A vaccination program would prevent 34000 cases of C trachomatis infection and 5976 cases of pelvic inflammatory disease. CONCLUSIONS: A C trachomatis vaccination program results in increased cost to the healthcare system but averts significant morbidity and death.