EHR-Based Care Coordination Performance Measures in Ambulatory Care

Describes electronic health record-based measures for assessing coordination in referrals, including information communicated with referral, communication to patient, and specialist report to primary care physician. Offers preliminary evaluation findings

Performance Measures Using Electronic Health Records: Five Case Studies

Presents the experiences of five provider organizations in developing, testing, and implementing four types of electronic quality-of-care indicators based on EHR data. Discusses challenges, and compares results with those from traditional indicators

SARS Transmission among Hospital Workers in Hong Kong

Despite infection control measures, breakthrough transmission of severe acute respiratory syndrome (SARS) occurred for many hospital workers in Hong Kong. We conducted a case-control study of 72 hospital workers with SARS and 144 matched controls. Inconsistent use of goggles, gowns, gloves, and caps was associated with a higher risk for SARS infection (unadjusted odds ratio 2.42 to 20.54, p < 0.05). The likelihood of SARS infection was strongly associated with the amount of personal protection equipment perceived to be inadequate, having <2 hours of infection control training, and not understanding infection control procedures. No significant differences existed between the case and control groups in the proportion of workers who performed high-risk procedures, reported minor protection equipment problems, or had social contact with SARS-infected persons. Perceived inadequacy of personal protection equipment supply, infection control training <2 hours, and inconsistent use of personal protection equipment when in contact with SARS patients were significant independent risk factors for SARS infection

What is the Role of Community Capabilities for Maternal Health? An Exploration of Community Capabilities as Determinants to Institutional Deliveries in Bangladesh, India, and Uganda

Background: While community capabilities are recognized as important factors in developing resilient health systems and communities, appropriate metrics for these have not yet been developed. Furthermore, the role of community capabilities on access to maternal health services has been underexplored. In this paper, we summarize the development of a community capability score based on the Future Health System (FHS) project’s experience in Bangladesh, India, and Uganda, and, examine the role of community capabilities as determinants of institutional delivery in these three contexts. Methods: We developed a community capability score using a pooled dataset containing cross-sectional household survey data from Bangladesh, India, and Uganda. Our main outcome of interest was whether the woman delivered in an institution. Our predictor variables included the community capability score, as well as a series of previously identified determinants of maternal health. We calculate both population-averaged effects (using GEE logistic regression), as well as sub-national level effects (using a mixed effects model). Results: Our final sample for analysis included 2775 women, of which 1238 were from Bangladesh, 1199 from India, and 338 from Uganda. We found that individual-level determinants of institutional deliveries, such as maternal education, parity, and ante-natal care access were significant in our analysis and had a strong impact on a woman’s odds of delivering in an institution. We also found that, in addition to individual-level determinants, greater community capability was significantly associated with higher odds of institutional delivery. For every additional capability, the odds of institutional delivery would increase by up to almost 6 %. Conclusion: Individual-level characteristics are strong determinants of whether a woman delivered in an institution. However, we found that community capability also plays an important role, and should be taken into account when designing programs and interventions to support institutional deliveries. Consideration of individual factors and the capabilities of the communities in which people live would contribute to the vision of supporting people-centered approaches to health

Validity and usefulness of members reports of implementation progress in a quality improvement initiative: findings from the Team Check-up Tool (TCT)

<p>Abstract</p> <p>Background</p> <p>Team-based interventions are effective for improving safety and quality of healthcare. However, contextual factors, such as team functioning, leadership, and organizational support, can vary significantly across teams and affect the level of implementation success. Yet, the science for measuring context is immature. The goal of this study is to validate measures from a short instrument tailored to track dynamic context and progress for a team-based quality improvement (QI) intervention.</p> <p>Methods</p> <p>Design: Secondary cross-sectional and longitudinal analysis of data from a clustered randomized controlled trial (RCT) of a team-based quality improvement intervention to reduce central line-associated bloodstream infection (CLABSI) rates in intensive care units (ICUs).</p> <p>Setting: Forty-six ICUs located within 35 faith-based, not-for-profit community hospitals across 12 states in the U.S.</p> <p>Population: Team members participating in an ICU-based QI intervention.</p> <p>Measures: The primary measure is the Team Check-up Tool (TCT), an original instrument that assesses context and progress of a team-based QI intervention. The TCT is administered monthly. Validation measures include CLABSI rate, Team Functioning Survey (TFS) and Practice Environment Scale (PES) from the Nursing Work Index.</p> <p>Analysis: Temporal stability, responsiveness and validity of the TCT.</p> <p>Results</p> <p>We found evidence supporting the temporal stability, construct validity, and responsiveness of TCT measures of intervention activities, perceived group-level behaviors, and barriers to team progress.</p> <p>Conclusions</p> <p>The TCT demonstrates good measurement reliability, validity, and responsiveness. By having more validated measures on implementation context, researchers can more readily conduct rigorous studies to identify contextual variables linked to key intervention and patient outcomes and strengthen the evidence base on successful spread of efficacious team-based interventions. QI teams participating in an intervention should also find data from a validated tool useful for identifying opportunities to improve their own implementation.</p

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis