Brigham and Women's Hospital
  • Boston, United States
Recent publications
Repeat expansion disorders are complex, primarily neurological, conditions deriving from repetition of nucleotide stretches. These disorders exhibit a wide range of clinical manifestations, many characterized by the presence of ataxia or lack of coordination. The most common of these entail an expansion of trinucleotide repeats in coding regions of certain genes resulting in a pathologic polyglutamine-expanded protein. Other mechanisms include peptides generated from noncanonical translation, repeat expansions in noncoding regions, which perturb gene expression, or the generation of toxic RNA intermediates. A multitude of factors, including repeat length, genomic location, and disruption of endogenous gene function are thought to drive pathology from the subcellular level to the clinical patient phenotypes. In this chapter, we attempt to unravel this complexity, beginning with the pathophysiological ramifications of repeat expansion disorders at the nucleotide level and working our way to anatomic consequences and patient-level presentations. We comment on therapeutic efforts of the past and provide some perspective on novel genetic treatments and clinical trial redesign that pave the way for the future.
Purpose: To assess the impact of periprocedural factors, including adverse events, on overall patient survival following image-guided liver tumor cryoablation procedures. Methods: In this retrospective single-institution study, 143 patients (73 male, 70 female, ages 29-88) underwent 169 image-guided liver tumor cryoablation procedures between October 1998 and August 2014. Patient, tumor and procedural variables were recorded. The primary outcome was overall survival post-procedure (Kaplan-Meier analysis). Secondary outcomes were the impact of 15 variables on patient survival, which were assessed with multivariate cox regression and log-rank tests. Results: Mean tumor diameter was 2.5 ± 1.2 cm. 26 of 143 (18.2%) patients had primary hepatic malignancies; 117 of 143 (81.8%) had liver metastases. Survival analysis revealed survivor functions at 3, 5, 7, 10 and 12 years post-ablation of 0.54, 0.37, 0.30, 0.17 and 0.06, with mean survival time of 40.8 ± 4.9 months. Tumor size ≥4 cm (p = .018), pre-procedural platelet count <100 × 103/μL (p = .023), and prior local radiation therapy (p = .014) were associated with worse overall patient survival. Grade 3 or higher adverse events were not associated with reduced survival (p = .49). Conclusions: All variables associated with overall survival were patient-related and none were associated with the cryoablation procedure. Pre-procedural thrombocytopenia, larger tumor size and history of prior local radiation therapy were independent risk factors for reduced overall survival in patients undergoing hepatic cryoablation. Adverse events related to hepatic cryoablation were not associated with decreased survival.
Background: Physical activity is critical for preventing and treating Type 2 diabetes (T2D). It is important to identify different profiles of physical activity change among those participating in behavioral interventions to optimize intervention-person fit. Methods: This study analyzes longitudinal trajectories of change in moderate-to-vigorous physical activity (MVPA) in a positive psychology (PP) and motivational interviewing (MI) intervention for T2D, using latent growth curve modeling (LGCM). Objective measures of MVPA were collected using accelerometers at three time points: pre-intervention, immediately post-intervention, and eight weeks post-intervention. LGCM analyses identified subpopulations of participants who responded similarly to the intervention and examined if sociodemographic, medical and psychosocial characteristics were associated with MVPA trajectories. Results: Analyses included 47 participants with complete follow-ups: 49% male, 81% non-Hispanic white, average age 66.1 (SD = 10.1). Overall, 36% of the participants increased MVPA while 57% did not. LGCM identified three profiles with distinct MVPA trajectories. Profile 1 ('Started Low, No Change'; 65.8% of participants) with a starting mean of 4.54 min of MVPA/day and decreased by -3.36 min. Profile 2 ('Moderate-High Start, Minimal Change,' 27.4% of participants) and had a starting mean of 22.86 min/day of MVPA with an average increase of 1.03 min. Profile 3 ('Moderate Start, Ended High'; 6.8% of participants), had a starting mean of 7.33 min MVPA/day, and increased by 28.4 min. Being male, younger, having fewer medical and psychiatric comorbidities were associated with increases in MVPA. Conclusions: This secondary analysis detected three distinct physical activity profiles during and after a PP-MI intervention. Future interventions can target individuals with characteristics that showed the greatest benefit and add additional supports to people in groups that did not increase physical activity as much. These findings show a need for targeted and sustained behavior change strategies during and after physical activity interventions. Trial registration:; identifier: NCT03001999.
Background Although prior reports have evaluated the clinical and cost impacts of cardiovascular magnetic resonance (CMR) for low-to-intermediate-risk patients with suspected significant coronary artery disease (CAD), the cost-effectiveness of CMR compared to relevant comparators remains poorly understood. We aimed to summarize the cost-effectiveness literature on CMR for CAD and create a cost-effectiveness calculator, useable worldwide, to approximate the cost-per-quality-adjusted-life-year (QALY) of CMR and relevant comparators with context-specific patient-level and system-level inputs. Methods We searched the Tufts Cost-Effectiveness Analysis Registry and PubMed for cost-per-QALY or cost-per-life-year-saved studies of CMR to detect significant CAD. We also developed a linear regression meta-model (CMR Cost-Effectiveness Calculator) based on a larger CMR cost-effectiveness simulation model that can approximate CMR lifetime discount cost, QALY, and cost effectiveness compared to relevant comparators [such as single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA)] or invasive coronary angiography. Results CMR was cost-effective for evaluation of significant CAD (either health-improving and cost saving or having a cost-per-QALY or cost-per-life-year result lower than the cost-effectiveness threshold) versus its relevant comparator in 10 out of 15 studies, with 3 studies reporting uncertain cost effectiveness, and 2 studies showing CCTA was optimal. Our cost-effectiveness calculator showed that CCTA was not cost-effective in the US compared to CMR when the most recent publications on imaging performance were included in the model. Conclusions Based on current world-wide evidence in the literature, CMR usually represents a cost-effective option compared to relevant comparators to assess for significant CAD.
While COVID-19 diagnosis and prognosis artificial intelligence models exist, very few can be implemented for practical use given their high risk of bias. We aimed to develop a diagnosis model that addresses notable shortcomings of prior studies, integrating it into a fully automated triage pipeline that examines chest radiographs for the presence, severity, and progression of COVID-19 pneumonia. Scans were collected using the DICOM Image Analysis and Archive, a system that communicates with a hospital’s image repository. The authors collected over 6,500 non-public chest X-rays comprising diverse COVID-19 severities, along with radiology reports and RT-PCR data. The authors provisioned one internally held-out and two external test sets to assess model generalizability and compare performance to traditional radiologist interpretation. The pipeline was evaluated on a prospective cohort of 80 radiographs, reporting a 95% diagnostic accuracy. The study mitigates bias in AI model development and demonstrates the value of an end-to-end COVID-19 triage platform.
Delivery of serious illness communication (SIC) is necessary to ensure that all seriously ill patients receive goal-concordant care. However, the current SIC delivery process contains barriers that prevent the delivery of timely and effective SIC. In this paper, we describe the current bottlenecks of the traditional SIC workflow and explore how a hybrid artificial intelligence-human workflow may improve the efficiency and effectiveness of SIC delivery in busy practice settings.
In recent years, the number of digital health tools with the potential to significantly improve delivery of healthcare services has grown tremendously. However, the use of these tools in large, complex health systems remains comparatively limited. The adoption and implementation of digital health tools at an enterprise level is a challenge; few strategies exist to help tools cross the chasm from clinical validation to integration within the workflows of a large health system. Many previously proposed frameworks for digital health implementation are difficult to operationalize in these dynamic organizations. In this piece, we put forth nine dimensions along which clinically validated digital health tools should be examined by health systems prior to adoption, and propose strategies for selecting digital health tools and planning for implementation in this setting. By evaluating prospective tools along these dimensions, health systems can evaluate which existing digital health solutions are worthy of adoption, ensure they have sufficient resources for deployment and long-term use, and devise a strategic plan for implementation.
Introduction Older adults face several challenges when transitioning from acute hospitals to community-based care. The PHARMacist Discharge Care (PHARM-DC) intervention is a pharmacist-led Transitions of Care (TOC) program intended to reduce 30-day hospital readmissions and emergency department visits at two large hospitals. This study used the Consolidated Framework for Implementation Research (CFIR) framework to evaluate pharmacist perceptions of the PHARM-DC intervention. Methods Intervention pharmacists and pharmacy administrators were purposively recruited by study team members located within each participating institution. Study team members located within each institution coordinated with two study authors unaffiliated with the institutions implementing the intervention to conduct interviews and focus groups remotely via telecommunication software. Interviews were recorded and transcribed, with transcriptions imported into NVivo for qualitative analysis. Qualitative analysis was performed using an iterative process to identify “a priori” constructs based on CFIR domains (intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation) and to create overarching themes as identified during coding. Results In total, ten semi-structured interviews and one focus group were completed across both hospitals. At Site A, six interviews were conducted with intervention pharmacists and pharmacists in administrative roles. Also at Site A, one focus group comprised of five intervention pharmacists was conducted. At Site B, interviews were conducted with four intervention pharmacists and pharmacists in administrative roles. Three overarching themes were identified: PHARM-DC and Institutional Context, Importance of PHARM-DC Adaptability, and Recommendations for PHARM-DC Improvement and Sustainability. Increasing pharmacist support for technical tasks and navigating pharmacist-patient language barriers were important to intervention implementation and delivery. Identifying cost-savings and quantifying outcomes as a result of the intervention were particularly important when considering how to sustain and expand the PHARM-DC intervention. Conclusion The PHARM-DC intervention can successfully be implemented at two institutions with considerable variations in TOC initiatives, resources, and staffing. Future implementation of PHARM-DC interventions should consider the themes identified, including an examination of institution-specific contextual factors such as the roles that pharmacy technicians may play in TOC interventions, the importance of intervention adaptability to account for patient needs and institutional resources, and pharmacist recommendations for intervention improvement and sustainability. Trial registration NCT04071951 .
Background Patient-reported outcomes (PROs) are used increasingly in routine clinical care and inform policies, reimbursements, and quality improvement. Less is known regarding PRO implementation in routine clinical care for diverse and underrepresented patient populations. Objective This review aims to identify studies of PRO implementation in diverse and underrepresented patient populations, elucidate representation of clinical specialties, assess implementation outcomes, and synthesize patient needs, concerns, and preferences. Methods MEDLINE, Embase, Web of Science, CINAHL, and PsycINFO were searched September 2021 for studies aiming to study PRO implementation in diverse and underrepresented patient populations within the United States. Studies were screened and data extracted by three independent reviewers. Implementation outcomes were assessed according to Proctor et al. taxonomy. A descriptive analysis of data was conducted. Results The search yielded 8,687 records, and 28 studies met inclusion criteria. The majority were observational cohort studies (n = 21, 75%) and conducted in primary care (n = 10, 36%). Most studies included majority female (n = 19, 68%) and non-White populations (n = 15, 54%), while fewer reported socioeconomic (n = 11, 39%) or insurance status (n = 9, 32.1%). Most studies assessed implementation outcomes of feasibility (n = 27, 96%) and acceptability (n = 19, 68%); costs (n = 3, 11%), penetration (n = 1, 4%), and sustainability (n = 1, 4%) were infrequently assessed. Conclusion PRO implementation in routine clinical care for diverse and underrepresented patient populations is generally feasible and acceptable. Research is lacking in key clinical specialties. Further work is needed to understand how health disparities drive PRO implementation outcomes.
Background Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described. Methods We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan–Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation. Results 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5–7 days/week and 300(13%) 2–3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5–7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5–7 vs. 2–3 days/week (HR = 0.68; 95% CI = 0.51—0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5–7 days/week vs. 2–3 days/week (HR 0.75, 95%CI 0.55–1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83–2.45; P = 0.20). Conclusions TB treatment 5–7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2–3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.
Palliative care is an interdisciplinary care to optimize physical, psychosocial, and spiritual symptoms of patients and their families whose quality of life is impaired by serious, life-limiting illness. In 2021, the importance of providing palliative care in the intensive care unit (ICU) is well recognized by various studies to alleviate physical symptoms due to invasive treatments, to set patient-centered goals of care, and to provide end-of-life care. This paper summarizes the evidence known to date on primary palliative care delivered in the ICU settings. We will then discuss the potential benefits and harms of primary palliative care so that critical care clinicians are better equipped to decide what services might best improve the palliative care needs in their ICUs.
Background Hospital- and community-onset sepsis are significant sepsis subgroups. Japanese data comparing these subgroups are limited. This study aimed to describe the epidemiology of hospital- and community-onset sepsis in critical care units in Japan. Methods We performed a retrospective cohort study using the Japanese Diagnosis and Procedure Combination database. Adult patients admitted to critical care units with sepsis from April 2010 to March 2020 were included. Sepsis cases were identified based on ICD-10 codes for infectious diseases, procedure codes for blood culture tests, and medication codes for antimicrobials. Patients’ characteristics, in-hospital mortality, and resource utilization were assessed. The in-hospital mortality between groups was compared using the Poisson regression generalized linear mixed-effect model. Results Of 516,124 patients, 52,183 (10.1%) had hospital-onset sepsis and 463,940 (89.9%) had community-onset sepsis. Hospital-onset sepsis was characterized by younger age, infrequent emergency hospitalization, frequent surgery under general anesthesia, and frequent organ support upon critical care unit admission compared to community-onset sepsis. In-hospital mortality was higher for hospital-onset than for community-onset sepsis (35.5% versus 19.2%; unadjusted mean difference, 16.3% [95% confidence interval (CI) 15.9–16.7]; adjusted mean difference, 15.6% [95% CI 14.9–16.2]). Mean hospital length of stay was longer for hospital-onset than for community-onset sepsis (47 days versus 30 days; unadjusted mean difference, 17 days [95% CI 16–17]; adjusted mean difference, 13 days [95% CI 12–14]). Conclusion Patients with hospital-onset sepsis admitted to critical care units in Japan had a poorer prognosis and more resource utilization including organ support rate, number of days with critical care unit surcharge codes, and hospital length of stay than those with community-onset sepsis.
Background Patients with cancer constitute a large and increasing segment of patients who receive unscheduled hospital-based care due to treatment-related symptoms and disease progression. The initial hospital-based touchpoint for these unscheduled hospitalizations is often the emergency department. Traditional models of emergency department and inpatient hospital-based care are saturated and incapable of scaling to accommodate the future, increased needs projected for this population. New models of care are necessary to address this gap. Acute home-based care is a promising tool potentially providing patient-centric, efficient care to eligible patients. Methods We applied Porter’s Five Forces framework that addresses the bargaining power of buyers and suppliers, threat of substitutes and new entrants, and industry rivalries plus the sixth force of regulation to clarify the factors that will promote or challenge the adoption of a home-based cancer care referral model before or following emergency department visits. Exploring this framework provides insights into the complexities of scaling an acute home-based cancer care model and highlights ways for health systems including hospitals, emergency departments, physician groups, and individual emergency physicians and oncologists to optimize their roles in this emerging model of care. Results We found that current workforce shortages, as well as workflow, infrastructure, and regulatory complexities, pose major challenges that unless carefully addressed may restrict the growth of acute home-based cancer care. Additional uncertainties persist around appropriate payment models and the competitive landscape. Key promoting factors include the recognized need in the cancer community and among payers for new models to decrease unscheduled hospitalizations and emergency department visits as well as the uptake of home-based and technology-enabled solutions during the COVID-19 pandemic. A better understanding of these forces helps to clarify the risks and opportunities as new entrants build their programs. Conclusions Acute home-based cancer care is a promising tool to complement traditional outpatient clinics, emergency departments, and inpatient hospital-based models of cancer care. New technologies and policies increasingly enable a broader scope of cancer care in the home setting.
The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). “Cases of SCMR” is a case series hosted on the SCMR website ( ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. The COVID-19 Case Collection highlights the impact of coronavirus disease 2019 (COVID-19) on the heart as demonstrated on CMR. Each case in series consists of the clinical presentation and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2021 Cases of SCMR and the 2020 and 2021 COVID-19 Case Collection series of nine cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar literature search engine.
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2,733 members
Hoda Javadikasgari
  • Cardiothoracic Surgery
Joselyn Joanna Rojas Quintero
  • Division of Pulmonary and Critical Care Medicine
Manish Chandra Choudhary
  • Department of Medicine
Sumit Gupta
  • Carl J. and Ruth Shapiro Cardiovascular Center
Venkat Vuddanda
  • Division of General Internal Medicine and Primary Care
Boston, United States