Publications by authors named "David M Levine"

106 Publications

Genetic Variants Associated with Inflammatory Bowel Disease and Gut Graft-versus-host Disease.

Blood Adv 2021 Sep 17. Epub 2021 Sep 17.

University of Washington, United States.

Previous studies have identified genetic variants associated with inflammatory bowel disease (IBD). We tested the hypothesis that some of these variants are also associated with the risk of moderate to severe gut graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Associations were evaluated initially in a discovery cohort of 1980 HCT recipients of European ancestry with HLA-matched related or unrelated donors. Associations discovered in this cohort were tested for replication in a separate cohort of 1294 HCT recipients. Among the 296 single nucleotide polymorphisms SNPs and 26 HLA alleles tested, we found that the recipient rs1260326 homozygous T allele in GCKR was associated with a higher risk of stage 2-4 gut GVHD. No other candidate variants were associated with stage 2-4 gut GVHD. The rs1260326 variant resides in an IBD-associated locus containing FNDC4, a gene that encodes a secreted anti-inflammatory factor that dampens macrophage activity and improves colitis in mice. Our results suggest that targeting inflammatory macrophages with recombinant FNDC4 offers an attractive avenue of clinical investigation for management of IBD and gut GVHD.
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http://dx.doi.org/10.1182/bloodadvances.2021004959DOI Listing
September 2021

The underappreciated success of home-based primary care: Next steps for CMS' Independence at Home.

J Am Geriatr Soc 2021 Aug 25. Epub 2021 Aug 25.

Division of Geriatric Medicine and Gerontology, Center for Transformative Geriatric Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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http://dx.doi.org/10.1111/jgs.17426DOI Listing
August 2021

Telehealth in US hospitals: State-level reimbursement policies no longer influence adoption rates.

Int J Med Inform 2021 09 22;153:104540. Epub 2021 Jul 22.

Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Objectives: Prior to COVID-19, levels of adoption of telehealth were low in the U.S., though they exploded during the pandemic. Following the pandemic, it will be critical to identify the characteristics that were associated with adoption of telehealth prior to the pandemic as key drivers of adoption and outside of a public health emergency.

Materials And Methods: We examined three data sources: The American Telemedicine Association's 2019 state telehealth analysis, the American Hospital Association's 2018 annual survey of acute care hospitals and its Information Technology Supplement. Telehealth adoption was measured through five telehealth categories. Independent variables included seven hospital characteristics and five reimbursement policies. After bivariate comparisons, we developed a multivariable model using logistic regression to assess characteristics associated with telehealth adoption.

Results: Among 2923 US hospitals, 73% had at least one telehealth capability. More than half of these hospitals invested in telehealth consultation services and stroke care. Non-profit hospitals, affiliated hospitals, major teaching hospitals, and hospitals located in micropolitan areas (those with 10-50,000 people) were more likely to adopt telehealth. In contrast, hospitals that lacked electronic clinical documentation, were unaffiliated with a hospital system, or were investor-owned had lower odds of adopting telehealth. None of the statewide policies were associated with adoption of telehealth.

Conclusions: Telehealth policy requires major revisions soon, and we suggest that these policies should be national rather than at the state level. Further steps as incentivizing rural hospitals for adopting interoperable systems and expanding RPM billing opportunities will help drive adoption, and promote equity.
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http://dx.doi.org/10.1016/j.ijmedinf.2021.104540DOI Listing
September 2021

Home hospital as a disposition for older adults from the emergency department: Benefits and opportunities.

J Am Coll Emerg Physicians Open 2021 Aug 21;2(4):e12517. Epub 2021 Jul 21.

Harvard Medical School Boston Massachusetts USA.

The $1 trillion industry of acute hospital care in the United States is shifting from inside the walls of the hospital to patient homes. To tackle the limitations of current hospital care in the United States, on November 25, 2020, the Center for Medicare & Medicaid Services announced that the acute hospital care at home waiver would reimburse for "home hospital" services. A "home hospital" is the home-based provision of acute services usually associated with the traditional inpatient hospital setting. Prior work suggests that home hospital care can reduce costs, maintain quality and safety, and improve patient experiences for select acutely ill adults who require hospital-level care. However, most emergency physicians are unfamiliar with the evidence of benefits demonstrated by home hospital services, especially for older adults. Therefore, the lead author solicited narrative inputs on this topic from selected experts in emergency medicine and home hospital services with clinical experience, publications, and funding on home hospital care. Then we sought to identify information most relevant to the practice of emergency medicine. We outline the proven and potential benefits of home hospital services specific to older adults compared to traditional acute care hospitalization with a focus on the emergency department.
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http://dx.doi.org/10.1002/emp2.12517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295243PMC
August 2021

Microwave Radiometry at Frequencies From 500 to 1400 MHz: An Emerging Technology for Earth Observations.

IEEE J Sel Top Appl Earth Obs Remote Sens 2021 14;14:4894-4914. Epub 2021 Apr 14.

NASA Jet Propulsion Laboratory, Pasadena, CA 91109 USA.

Microwave radiometry has provided valuable spaceborne observations of Earth's geophysical properties for decades. The recent SMOS, Aquarius, and SMAP satellites have demonstrated the value of measurements at 1400 MHz for observing surface soil moisture, sea surface salinity, sea ice thickness, soil freeze/thaw state, and other geophysical variables. However, the information obtained is limited by penetration through the subsurface at 1400 MHz and by a reduced sensitivity to surface salinity in cold or wind-roughened waters. Recent airborne experiments have shown the potential of brightness temperature measurements from 500-1400 MHz to address these limitations by enabling sensing of soil moisture and sea ice thickness to greater depths, sensing of temperature deep within ice sheets, improved sensing of sea salinity in cold waters, and enhanced sensitivity to soil moisture under vegetation canopies. However, the absence of significant spectrum reserved for passive microwave measurements in the 500-1400 MHz band requires both an opportunistic sensing strategy and systems for reducing the impact of radio-frequency interference. Here, we summarize the potential advantages and applications of 500-1400 MHz microwave radiometry for Earth observation and review recent experiments and demonstrations of these concepts. We also describe the remaining questions and challenges to be addressed in advancing to future spaceborne operation of this technology along with recommendations for future research activities.
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http://dx.doi.org/10.1109/jstars.2021.3073286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244653PMC
April 2021

Predictors and Reasons Why Patients Decline to Participate in Home Hospital: a Mixed Methods Analysis of a Randomized Controlled Trial.

J Gen Intern Med 2021 May 5. Epub 2021 May 5.

Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, MA, USA.

Background: Acute care at home ("home hospital") compared to traditional hospital care has been shown to lower cost, utilization, and readmission and improve patient experience and physical activity. Despite these benefits, many patients decline to enroll in home hospital.

Objective: Describe predictors and reasons why patients decline home hospital.

Design: Mixed methods evaluation of a randomized controlled trial.

Participants: Patients in the emergency department who required admission and were accepted for home hospital by the home hospital attending, but ultimately declined to enroll.

Intervention: Home hospital care, including nurse and physician home visits, intravenous medications, remote monitoring, video communication, and point-of-care testing.

Approach: We conducted a thematic content analysis of verbatim reasons for decline. We performed bivariate comparisons then multivariable logistic regression to identify patient characteristics associated with declining participation.

Key Results: Two hundred forty-eight patients were eligible to enroll, and 157 (63%) declined enrollment. Patients who declined and enrolled were of similar age (median age, 74 vs 75 years old; p = 0.27), sex (32% vs 36% female; p = 0.49), and race/ethnicity (p = 0.26). In multivariable analysis, patients were significantly more likely to decline if they initially presented at the community hospital compared to the academic medical center (53% vs 42%; adjusted OR, 2.2 [95% CI, 1.2 to 4.2]) and if single (37% v 24%; adjusted OR, 2.5 [95% CI, 1.2 to 5.1]). We formulated 10 qualitative categories describing reasons patients ultimately declined. Many patients declined because they felt it was easier to remain in the hospital (20%) or felt safer in the hospital than in their home (20%).

Conclusions: Patients who declined to enroll in a home hospital intervention had similar sociodemographic characteristics as enrollees except partner status and declined most often for perceptions surrounding safety at home and the ease of remaining in the hospital.

Trial Registration: NCT03203759.
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http://dx.doi.org/10.1007/s11606-021-06833-2DOI Listing
May 2021

Home Hospital for Surgery.

JAMA Surg 2021 Jul;156(7):679-680

Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamasurg.2021.0597DOI Listing
July 2021

Assessment of Diagnosis and Triage in Validated Case Vignettes Among Nonphysicians Before and After Internet Search.

JAMA Netw Open 2021 03 1;4(3):e213287. Epub 2021 Mar 1.

Harvard Medical School, Boston, Massachusetts.

Importance: When confronted with new medical symptoms, many people turn to the internet to understand why they are ill as well as whether and where they should get care. Such searches may be harmful because they may facilitate misdiagnosis and inappropriate triage.

Objective: To empirically measure the association of an internet search for health information with diagnosis, triage, and anxiety by laypeople.

Design, Setting, And Participants: This survey study used a nationally representative sample of US adults who were recruited through an online platform between April 1, 2019, and April 15, 2019. A total of 48 validated case vignettes of both common (eg, viral illness) and severe (eg, heart attack) conditions were used. Participants were asked to relay their diagnosis, triage, and anxiety regarding 1 of these cases before and after searching the internet for health information.

Exposures: Short, validated case vignettes written at or below the sixth-grade reading level randomly assigned to participants.

Main Outcomes And Measures: Correct diagnosis, correct triage, and flipping (changing) or anchoring (not changing) diagnosis and triage decisions were the main outcomes. Multivariable modeling was performed to identify patient factors associated with correct triage and diagnosis.

Results: Of the 5000 participants, 2549 were female (51.0%), 3819 were White (76.4%), and the mean (SD) age was 45.0 (16.9) years. Mean internet search time was 12.1 (95% CI, 10.7-13.5) minutes per case. No difference in triage accuracy was found before and after search (74.5% vs 74.1%; difference, -0.4 [95% CI, -1.4 to 0.6]; P = .06), but improved diagnostic accuracy was found (49.8% vs 54.0%; difference, 4.2% [95% CI, 3.1%-5.3%]; P < .001). Most participants (4254 [85.1%]) were anchored on their diagnosis. Of the 14.9% of participants (n = 746) who flipped their diagnosis, 9.6% (n = 478) flipped from incorrect to correct and 5.4% (n = 268) flipped from correct to incorrect. The following groups had an increased rate of correct diagnosis: adults 40 years or older (eg, 40-49 years: 5.1 [95% CI, 0.8-9.4] percentage points better than those aged <30 years; P = .02), women (9.4 [95% CI, 6.8-12.0] percentage points better than men; P < .001), and those with perceived poor health status (16.3 [95% CI, 6.9-25.6] percentage points better than those with excellent status; P = .001) and with more than 2 chronic diseases (6.8 [95% CI, 1.5-12.1] percentage points better than those with 0 conditions; P = .01).

Conclusions And Relevance: This study found that an internet search for health information was associated with small increases in diagnostic accuracy but not with triage accuracy.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008286PMC
March 2021

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

Gut 2021 Jul 25;70(7):1325-1334. Epub 2021 Feb 25.

Cancer Prevention and Control Program, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.

Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.

Results: We identified 13 loci that reached genome-wide significance (p<5×10) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.

Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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http://dx.doi.org/10.1136/gutjnl-2020-321534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223655PMC
July 2021

Randomized controlled study using text messages to help connect new medicaid beneficiaries to primary care.

NPJ Digit Med 2021 Feb 15;4(1):26. Epub 2021 Feb 15.

Harvard Medical School, Boston, MA, USA.

Accessing primary care is often difficult for newly insured Medicaid beneficiaries. Tailored text messages may help patients navigate the health system and initiate care with a primary care physician. We conducted a randomized controlled trial of tailored text messages with newly enrolled Medicaid managed care beneficiaries. Text messages included education about the importance of primary care, reminders to obtain an appointment, and resources to help schedule an appointment. Within 120 days of enrollment, we examined completion of at least one primary care visit and use of the emergency department. Within 1 year of enrollment, we examined diagnosis of a chronic disease, receipt of preventive care, and use of the emergency department. 8432 beneficiaries (4201 texting group; 4231 control group) were randomized; mean age was 37 years and 24% were White. In the texting group, 31% engaged with text messages. In the texting vs control group after 120 days, there were no differences in having one or more primary care visits (44.9% vs. 45.2%; difference, -0.27%; p = 0.802) or emergency department use (16.2% vs. 16.0%; difference, 0.23%; p = 0.771). After 1 year, there were no differences in diagnosis of a chronic disease (29.0% vs. 27.8%; difference, 1.2%; p = 0.213) or appropriate preventive care (for example, diabetes screening: 14.1% vs. 13.4%; difference, 0.69%; p = 0.357), but emergency department use (32.7% vs. 30.2%; difference, 2.5%; p = 0.014) was greater in the texting group. Tailored text messages were ineffective in helping new Medicaid beneficiaries visit primary care within 120 days.
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http://dx.doi.org/10.1038/s41746-021-00389-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884833PMC
February 2021

Hospital-Level Care at Home for Acutely Ill Adults: a Qualitative Evaluation of a Randomized Controlled Trial.

J Gen Intern Med 2021 07 21;36(7):1965-1973. Epub 2021 Jan 21.

Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, MA, USA.

Background: Substitutive hospital-level care in a patient's home ("home hospital") has been shown to lower cost, utilization, and readmission compared to traditional hospital care. However, patients' perspectives to help explain how and why interventions like home hospital accomplish many of these results are lacking.

Objective: Elucidate and explain patient perceptions of home hospital versus traditional hospital care to better describe the different perceptions of care in both settings.

Design: Qualitative evaluation of a randomized controlled trial.

Participants: 36 hospitalized patients (19 home; 17 control).

Intervention: Traditional hospital ("control") versus home hospital ("home"), including nurse and physician home visits, intravenous medications, remote monitoring, video communication, and point-of-care testing.

Approach: We conducted a thematic content analysis of semi-structured interviews. Team members developed a coding structure through a multiphase approach, utilizing a constant comparative method.

Key Results: Themes clustered around 3 domains: clinician factors, factors promoting healing, and systems factors. Clinician factors were similar in both groups; both described beneficial interactions with clinical staff; however, home patients identified greater continuity of care. For factors promoting healing, home patients described a locus of control surrounding their sleep, activity, and environmental comfort that control patients lacked. For systems factors, home patients experienced more efficient processes and logistics, particularly around admission and technology use, while both noted difficulty with discharge planning.

Conclusions: Compared to control patients, home patients had better experiences with their care team, had more experiences promoting healing such as better sleep and physical activity, and had better experiences with systems factors such as the admission processes. Potential explanations include continuity of care, the power and familiarity of the home, and streamlined logistics. Future improvements include enhanced care transitions and ensuring digital interfaces are usable.

Trial Registration: NCT03203759.
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http://dx.doi.org/10.1007/s11606-020-06416-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298744PMC
July 2021

Rural Perceptions of Acute Care at Home: A Qualitative Analysis.

J Rural Health 2021 03 13;37(2):353-361. Epub 2021 Jan 13.

General Practice and Primary Health Care, School of Population Health, University of Auckland, Auckland, New Zealand.

Purpose: Hospital-level care at home in urban areas delivers low-cost, high-quality care. Few have attempted to deliver home hospital care in a rural environment, where traditional hospitals are often less equipped to deliver high-quality care. Little is known about rural clinicians' and patients' perceptions regarding rural home hospital care and how the urban model might be adapted to fit rural circumstances.

Methods: We conducted semistructured qualitative interviews in the United States with a national purposive sample of practicing rural clinicians, a focus group with clinicians who care for rural patients, and interviews with rural patients. We coded these qualitative data into domains and subdomains.

Findings: We identified 4 domains: (1) current state of rural health care, (2) attitudes toward rural home hospital, (3) perceived barriers to implementing rural home hospital, and (4) perceived facilitators to implementing rural home hospital. Participants expressed challenges with current rural health care, including inefficient care coupled with poor access. Most felt rural home hospital care could offer benefits, including comfort, timeliness, and downstream outcomes such as readmission rate reduction. Rural patients were open to receiving acute care in their homes. Potential barriers included geographic accessibility, Internet connectivity, rural hospital politics, the culture of hospitalization, and the availability of skilled human resources.

Conclusions: Significant interest and optimism exist surrounding rural home hospital despite perceived barriers. Designing for and testing adaptations to the urban model will likely optimize benefits and minimize threats to a potential intervention.
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http://dx.doi.org/10.1111/jrh.12551DOI Listing
March 2021

You are What You Think Your Social Network Eats: Public Housing, Social Networks, and Fast-Food Consumption.

J Health Care Poor Underserved 2020 ;31(4):1712-1726

High-sodium diets (e.g., fast-food intake, FF) may contribute to increased hyper-tension risk among low-income populations. We examined the association between FF intake and perceived social-network member FF intake among Baltimore public housing residents. We analyzed 2014-2015 cross-sectional data. Our dependent variable was FF intake (eating FF weekly versus not), and our independent variable was perceiving one or more network member eating FF weekly. We used multivariable Poisson regression with robust variance, adjusted for individual and network covariates. The 266 public housing residents had mean age 44.5 years: 86.1% women, 95.5% African American, 56.8% hypertension, and 42.8% who ate FF weekly. Residents were significantly more likely to eat FF weekly if they perceived that their network contained one or more members who consumed FF weekly (relative risk 1.50, 95%CI 1.05-2.14, p=.02). Given the association between personal and social network consumption of FF weekly, further investigation may be warranted of novel social network interventions for dietary behavior change.
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http://dx.doi.org/10.1353/hpu.2020.0128DOI Listing
September 2021

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Carcinogenesis 2021 04;42(3):369-377

Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast, UK.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
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http://dx.doi.org/10.1093/carcin/bgaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052954PMC
April 2021

Derivation of a Clinical Risk Score to Predict 14-Day Occurrence of Hypoxia, ICU Admission, and Death Among Patients with Coronavirus Disease 2019.

J Gen Intern Med 2021 03 3;36(3):730-737. Epub 2020 Dec 3.

Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, MA, USA.

Background: Uncertainty surrounding COVID-19 regarding rapid progression to acute respiratory distress syndrome and unusual clinical characteristics make discharge from a monitored setting challenging. A clinical risk score to predict 14-day occurrence of hypoxia, ICU admission, and death is unavailable.

Objective: Derive and validate a risk score to predict suitability for discharge from a monitored setting among an early cohort of patients with COVID-19.

Design: Model derivation and validation in a retrospective cohort. We built a manual forward stepwise logistic regression model to identify variables associated with suitability for discharge and assigned points to each variable. Event-free patients were included after at least 14 days of follow-up.

Participants: All adult patients with a COVID-19 diagnosis between March 1, 2020, and April 12, 2020, in 10 hospitals in Massachusetts, USA.

Main Measures: Fourteen-day composite predicting hypoxia, ICU admission, and death. We calculated a risk score for each patient as a predictor of suitability for discharge evaluated by area under the curve.

Key Results: Of 2059 patients with COVID-19, 1326 met inclusion. The 1014-patient training cohort had a mean age of 58 years, was 56% female, and 65% had at least one comorbidity. A total of 255 (25%) patients were suitable for discharge. Variables associated with suitability for discharge were age, oxygen saturation, and albumin level, yielding a risk score between 0 and 55. At a cut point of 30, the score had a sensitivity of 83% and specificity of 82%. The respective c-statistic for the derivation and validation cohorts were 0.8939 (95% CI, 0.8687 to 0.9192) and 0.8685 (95% CI, 0.8095 to 0.9275). The score performed similarly for inpatients and emergency department patients.

Conclusions: A 3-item risk score for patients with COVID-19 consisting of age, oxygen saturation, and an acute phase reactant (albumin) using point of care data predicts suitability for discharge and may optimize scarce resources.
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http://dx.doi.org/10.1007/s11606-020-06353-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713904PMC
March 2021

Remote Patient Monitoring Program for Hospital Discharged COVID-19 Patients.

Appl Clin Inform 2020 10 25;11(5):792-801. Epub 2020 Nov 25.

Division of General Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.

Objective: We deployed a Remote Patient Monitoring (RPM) program to monitor patients with coronavirus disease 2019 (COVID-19) upon hospital discharge. We describe the patient characteristics, program characteristics, and clinical outcomes of patients in our RPM program.

Methods: We enrolled COVID-19 patients being discharged home from the hospital. Enrolled patients had an app, and were provided with a pulse oximeter and thermometer. Patients self-reported symptoms, O saturation, and temperature daily. Abnormal symptoms or vital signs were flagged and assessed by a pool of nurses. Descriptive statistics were used to describe patient and program characteristics. A mixed-effects logistic regression model was used to determine the odds of a combined endpoint of emergency department (ED) or hospital readmission.

Results: A total of 295 patients were referred for RPM from five participating hospitals, and 225 patients were enrolled. A majority of enrolled patients (66%) completed the monitoring period without triggering an abnormal alert. Enrollment was associated with a decreased odds of ED or hospital readmission (adjusted odds ratio: 0.54; 95% confidence interval: 0.3-0.97;  = 0.039). Referral without enrollment was not associated with a reduced odds of ED or hospital readmission.

Conclusion: RPM for COVID-19 provides a mechanism to monitor patients in their home environment and reduce hospital utilization. Our work suggests that RPM reduces readmissions for patients with COVID-19 and provides scalable remote monitoring capabilities upon hospital discharge. RPM for postdischarge patients with COVID-19 was associated with a decreased risk of readmission to the ED or hospital, and provided a scalable mechanism to monitor patients in their home environment.
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http://dx.doi.org/10.1055/s-0040-1721039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688410PMC
October 2020

Place of Death and End-of-Life Care Utilization among COVID-19 Decedents in a Massachusetts Health Care System.

J Palliat Med 2021 03 17;24(3):322-323. Epub 2020 Nov 17.

Division of General Internal Medicine and Primary Care, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1089/jpm.2020.0674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020559PMC
March 2021

Social network factors and cardiovascular health among baltimore public housing residents.

Prev Med Rep 2020 Dec 31;20:101192. Epub 2020 Aug 31.

Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Social networks - or the web of relationships between individuals - may influence cardiovascular disease risk, particularly in low-income urban communities that suffer from a high prevalence of cardiovascular disease. Our objective was to describe the social networks of public housing residents - a low-income urban population - in Baltimore, MD and the association between these networks and blood pressure. We used cross-sectional survey data of randomly selected heads of household in two public housing complexes in Baltimore, MD (8/2014-8/2015). Respondents answered questions about 10 social network members, including attributes of their relationship and the frequency of interaction between members. We calculated measures of network composition (e.g., proportion of network members who were family members) and network structure (e.g., density), which we then dichotomized as "high" (upper quartile) and "low" (less than upper quartile). We used linear regression to test the association between network measures and mean systolic and diastolic blood pressure. The sample included 259 respondents (response rate: 46.6%). Mean age was 44.4 years, 85.7% were women, 95.4% Black, and 56.0% had a history of hypertension. A high proportion of older children (age 8-17 years) in the network (>30%) was associated with a 4.0% (95%CI [0.07, 8.07], p = 0.047) higher mean systolic blood pressure (~4.9 mmHg greater). Other network attributes had no association with blood pressure. Social network attributes, such as having a high proportion of older children in one's network, may have particular relevance to blood pressure among low-income public housing residents, reinforcing the potential importance of social relationships to cardiovascular health.
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http://dx.doi.org/10.1016/j.pmedr.2020.101192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498937PMC
December 2020

Recipient and donor genetic variants associated with mortality after allogeneic hematopoietic cell transplantation.

Blood Adv 2020 07;4(14):3224-3233

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.

Many studies have suggested that genetic variants in donors and recipients are associated with survival-related outcomes after allogeneic hematopoietic cell transplantation (HCT), but these results have not been confirmed. Therefore, the utility of testing genetic variants in donors and recipients for risk stratification or understanding mechanisms leading to mortality after HCT has not been established. We tested 122 recipient and donor candidate variants for association with nonrelapse mortality (NRM) and relapse mortality (RM) in a cohort of 2560 HCT recipients of European ancestry with related or unrelated donors. Associations discovered in this cohort were tested for replication in a separate cohort of 1710 HCT recipients. We found that the donor rs1051792 A allele in MICA was associated with a lower risk of NRM. Donor and recipient rs1051792 genotypes were highly correlated, making it statistically impossible to determine whether the donor or recipient genotype accounted for the association. Risks of grade 3 to 4 graft-versus-host disease (GVHD) and NRM in patients with grades 3 to 4 GVHD were lower with donor MICA-129Met but not with MICA-129Val, implicating MICA-129Met in the donor as an explanation for the decreased risk of NRM after HCT. Our analysis of candidate variants did not show any other association with NRM or RM. A genome-wide association study did not identify any other variants associated with NRM or RM.
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http://dx.doi.org/10.1182/bloodadvances.2020001927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391140PMC
July 2020

Design and testing of a mobile health application rating tool.

NPJ Digit Med 2020 21;3:74. Epub 2020 May 21.

Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, MA USA.

Mobile health applications ("apps") have rapidly proliferated, yet their ability to improve outcomes for patients remains unclear. A validated tool that addresses apps' potentially important dimensions has not been available to patients and clinicians. The objective of this study was to develop and preliminarily assess a usable, valid, and open-source rating tool to objectively measure the risks and benefits of health apps. We accomplished this by using a Delphi process, where we constructed an app rating tool called THESIS that could promote informed app selection. We used a systematic process to select chronic disease apps with ≥4 stars and <4-stars and then rated them with THESIS to examine the tool's interrater reliability and internal consistency. We rated 211 apps, finding they performed fair overall (3.02 out of 5 [95% CI, 2.96-3.09]), but especially poorly for privacy/security (2.21 out of 5 [95% CI, 2.11-2.32]), interoperability (1.75 [95% CI, 1.59-1.91]), and availability in multiple languages (1.43 out of 5 [95% CI, 1.30-1.56]). Ratings using THESIS had fair interrater reliability ( = 0.3-0.6) and excellent scale reliability ( = 0.85). Correlation with traditional star ratings was low ( = 0.24), suggesting THESIS captures issues beyond general user acceptance. Preliminary testing of THESIS suggests apps that serve patients with chronic disease could perform much better, particularly in privacy/security and interoperability. THESIS warrants further testing and may guide software and policymakers to further improve app performance, so apps can more consistently improve patient outcomes.
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http://dx.doi.org/10.1038/s41746-020-0268-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242452PMC
May 2020

Physician Mothers and Breastfeeding: A Cross-Sectional Survey.

Breastfeed Med 2020 05 17;15(5):312-320. Epub 2020 Mar 17.

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

To explore infant-feeding intentions and behavior of physician mothers as well as their breastfeeding enablers and obstacles. A cross-sectional online survey was conducted among female physicians with at least one biological child recruited through the Academy of Breastfeeding Medicine. The main outcomes were duration of exclusive breastfeeding (EBF) and duration of any breastfeeding (BFD). We determined predictors of EBF and BFD. The 570 participants reported intention to breastfeed at least 12 months in 78.1% of cases. Breastfeeding rates were 97.8%, 85.5%, and 55.4% at birth, 6, and 12 months. EBF rates were 88.5%, 76.3%, and 40.9% at birth, 3, and 6 months. Younger participant age, breastfeeding discontinuation not due to work-related demands, and heightened maternal satisfaction with BFD were associated with longer EBF and BFD. EBF at birth, less maternal stress, availability of time to express milk, and collegial support were associated with longer EBF. Longer maternal BFD goal, longer maternity leave, existence of laws or regulations to support breastfeeding among working mothers, later child order, and lower level of maternal depression were associated with longer BFD. Maternal infant-feeding intentions and work-related factors both play important roles in physician mothers' infant-feeding behavior. Longer maternity leave, regulations to support breastfeeding among working mothers, and workplace support might significantly improve physician mothers' BFD.
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http://dx.doi.org/10.1089/bfm.2019.0193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235920PMC
May 2020

Social Network Intervention Reduces Added Sugar Intake Among Baltimore Public Housing Residents: A Feasibility Study.

Nutr Metab Insights 2020 2;13:1178638820909329. Epub 2020 Mar 2.

Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Public housing residents have high intake of added sugars, which is associated with sugar-sweetened beverage (SSB) consumption in their social networks. In this feasibility study, we designed and tested a network-oriented intervention to decrease added sugar intake by encouraging reduced SSB consumption. We conducted a 6-month single-arm trial testing a small-group curriculum (9 sessions) that combined behavior change strategies to reduce added sugar intake by promoting SSB reduction with a peer outreach approach. We recruited and trained public housing residents to be "Peer Educators," who then communicated information and made changes to reduce SSB with their network members. We calculated the median number of group sessions attended and determined the percentage of individuals satisfied with the program. We estimated added sugar intake using a 5-factor dietary screener and compared baseline and 6-month median values using Wilcoxon signed rank tests. We recruited 17 residents and 17 of their network members (n = 34). Mean age was 45.7 years, 79.4% were women, and 97.1% were African American. Median number of sessions attended was 9 (interquartile range: 4-9), and 88.2% were very satisfied with the program. Overall, baseline median added sugar intake was 38.0 tsp/day, which significantly declined to 17.2 tsp/day at 6 months ( < .001). Residents and network members achieved similar results at 6 months (17.4 vs 16.9 tsp/day, respectively). In conclusion, our results demonstrate that a social network intervention aimed at reducing SSB consumption is feasible and can produce significant decreases in adult added sugar intake, which warrants further investigation in a randomized controlled trial.
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http://dx.doi.org/10.1177/1178638820909329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052458PMC
March 2020

Hospital-Level Care at Home for Acutely Ill Adults: A Randomized Controlled Trial.

Ann Intern Med 2020 01 17;172(2):77-85. Epub 2019 Dec 17.

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (D.M.L., K.O., B.B., A.S., J.L.S.).

Background: Substitutive hospital-level care in a patient's home may reduce cost, health care use, and readmissions while improving patient experience, although evidence from randomized controlled trials in the United States is lacking.

Objective: To compare outcomes of home hospital versus usual hospital care for patients requiring admission.

Design: Randomized controlled trial. (ClinicalTrials.gov: NCT03203759).

Setting: Academic medical center and community hospital.

Patients: 91 adults (43 home and 48 control) admitted via the emergency department with selected acute conditions.

Intervention: Acute care at home, including nurse and physician home visits, intravenous medications, remote monitoring, video communication, and point-of-care testing.

Measurements: The primary outcome was the total direct cost of the acute care episode (sum of costs for nonphysician labor, supplies, medications, and diagnostic tests). Secondary outcomes included health care use and physical activity during the acute care episode and at 30 days.

Results: The adjusted mean cost of the acute care episode was 38% (95% CI, 24% to 49%) lower for home patients than control patients. Compared with usual care patients, home patients had fewer laboratory orders (median per admission, 3 vs. 15), imaging studies (median, 14% vs. 44%), and consultations (median, 2% vs. 31%). Home patients spent a smaller proportion of the day sedentary (median, 12% vs. 23%) or lying down (median, 18% vs. 55%) and were readmitted less frequently within 30 days (7% vs. 23%).

Limitation: The study involved 2 sites, a small number of home physicians, and a small sample of highly selected patients (with a 63% refusal rate among potentially eligible patients); these factors may limit generalizability.

Conclusion: Substitutive home hospitalization reduced cost, health care use, and readmissions while increasing physical activity compared with usual hospital care.

Primary Funding Source: Partners HealthCare Center for Population Health and internal departmental funds.
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http://dx.doi.org/10.7326/M19-0600DOI Listing
January 2020

Characteristics of Americans With Primary Care and Changes Over Time, 2002-2015.

JAMA Intern Med 2020 03;180(3):463-466

Harvard Medical School, Harvard University, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamainternmed.2019.6282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990950PMC
March 2020

Hypertension Self-management in Socially Disadvantaged African Americans: the Achieving Blood Pressure Control Together (ACT) Randomized Comparative Effectiveness Trial.

J Gen Intern Med 2020 01 8;35(1):142-152. Epub 2019 Nov 8.

Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.

Background: Effective hypertension self-management interventions are needed for socially disadvantaged African Americans, who have poorer blood pressure (BP) control compared to others.

Objective: We studied the incremental effectiveness of contextually adapted hypertension self-management interventions among socially disadvantaged African Americans.

Design: Randomized comparative effectiveness trial.

Participants: One hundred fifty-nine African Americans at an urban primary care clinic.

Interventions: Participants were randomly assigned to receive (1) a community health worker ("CHW") intervention, including the provision of a home BP monitor; (2) the CHW plus additional training in shared decision-making skills ("DoMyPART"); or (3) the CHW plus additional training in self-management problem-solving ("Problem Solving").

Main Measures: We assessed group differences in BP control (systolic BP (SBP) < 140 mm Hg and diastolic BP (DBP) < 90 mmHg), over 12 months using generalized linear mixed models. We also assessed changes in SBP and DBP and participants' BP self-monitoring frequency, clinic visit patient-centeredness (i.e., extent of patient-physician discussions focused on patient emotional and psychosocial concerns), hypertension self-management behaviors, and self-efficacy.

Key Results: BP control improved in all groups from baseline (36%) to 12 months (52%) with significant declines in SBP (estimated mean [95% CI] - 9.1 [- 15.1, - 3.1], - 7.4 [- 13.4, - 1.4], and - 11.3 [- 17.2, - 5.3] mmHg) and DBP (- 4.8 [- 8.3, - 1.3], - 4.0 [- 7.5, - 0.5], and - 5.4 [- 8.8, - 1.9] mmHg) for CHW, DoMyPART, and Problem Solving, respectively). There were no group differences in BP outcomes, BP self-monitor use, or clinic visit patient-centeredness. The Problem Solving group had higher odds of high hypertension self-care behaviors (OR [95% CI] 18.7 [4.0, 87.3]) and self-efficacy scores (OR [95% CI] 4.7 [1.5, 14.9]) at 12 months compared to baseline, while other groups did not. Compared to DoMyPART, the Problem Solving group had higher odds of high hypertension self-care behaviors (OR [95% CI] 5.7 [1.3, 25.5]) at 12 months.

Conclusion: A context-adapted CHW intervention was correlated with improvements in BP control among socially disadvantaged African Americans. However, it is not clear whether improvements were the result of this intervention. Neither the addition of shared decision-making nor problem-solving self-management training to the CHW intervention further improved BP control.

Trial Registry: ClinicalTrials.gov Identifier: NCT01902719.
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http://dx.doi.org/10.1007/s11606-019-05396-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957583PMC
January 2020

Burnout Among Staff in a Home Hospital Pilot.

J Clin Med Res 2019 Jul 11;11(7):484-488. Epub 2019 Jun 11.

Harvard Medical School; Boston, MA, USA.

Background: Burnout affects large portions of the healthcare workforce and is associated with increased medical errors, decreased patient experience and adherence, loss of professionalism, and decreased productivity. Little data exists on how novel clinical care settings might impact burnout. We studied the experience and burnout of staff involved in a home hospital pilot, where acutely ill patients were cared for at home as a substitute for traditional hospitalization.

Methods: We analyzed evaluations completed by home hospital staff (physicians, registered nurses, and research assistants) at the conclusion of a 2-month pilot program. Our primary outcome was burnout evaluated by the Mini Z Burnout Survey. Secondary outcomes included overall job satisfaction, work environment, workload, and team evaluation measured on a 5-point Likert scale.

Results: Eight of nine (89%) staff completed evaluations. Seven of eight (88%) staff had no symptoms of burnout; one (13%) was under stress but did not feel burned out. Median overall satisfaction with home hospital was 4.5/5.0 (interquartile range (IQR), 1.0). Most staff (6/8; 75%) "strongly agreed" that their professional values were well-aligned with the program. Three of six (50%) "entirely" or "very much" preferred home hospital to their standard clinical setting. Six of eight (75%) staff felt that their opinions were "entirely" heard; four of eight (50%) felt the team "entirely" valued each of its participants.

Conclusions: Novel clinical care settings like home hospital may lead to low staff burnout, high job satisfaction, and a healthy work environment. Further study is warranted.
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http://dx.doi.org/10.14740/jocmr3842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6575120PMC
July 2019

Maternal Implications of Breastfeeding: A Review for the Internist.

Am J Med 2019 08 7;132(8):912-920. Epub 2019 Mar 7.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md.

Breastfeeding seems to be a low-cost intervention that provides both short- and long-term health benefits for the breastfeeding woman. Interventions to support breastfeeding can increase its rate, exclusivity, and duration. Internists often have a longitudinal relationship with their patients and can be important partners with obstetricians and pediatricians in advocating for breastfeeding. To play their unique and critical role in breastfeeding promotion, internists need to be knowledgeable about breastfeeding and its maternal health benefits. In this paper, we review the short- and long-term maternal health benefits of breastfeeding. We also discuss special considerations in the care of breastfeeding women for the internist.
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http://dx.doi.org/10.1016/j.amjmed.2019.02.021DOI Listing
August 2019

Overweight/obesity among social network members has an inverse relationship with Baltimore public housing residents' BMI.

Prev Med Rep 2019 Jun 25;14:100809. Epub 2019 Jan 25.

Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

The American Heart Association has encouraged networks research focused on cardiovascular disease and its risk factors, such as obesity. However, little network research has focused on minorities or low-income populations. Our objective was to characterize the relationship between body mass index (BMI) with social network overweight/obesity among public housing residents in Baltimore, MD - a predominantly black, low-income group. We conducted a cross-sectional survey of randomly selected public housing residences (8/2014-8/2015). Adults had their height and weight measured and reported their network members' weight statuses using pictograms. Our dependent variable was respondents' BMI, and independent variable was perceived exposure to overweight/obesity in the social network. We also explored network exposure to overweight/obesity among 1) family members and 2) friends. We used multivariable linear regression adjusted for significant covariates. Our sample included 255 adults with mean age of 44.4 years, 85.5% women, 95.7% black, and mean BMI of 33.2 kg/m. Most network members were overweight/obese (56.1%). For every 1% increase in network exposure to overweight/obesity, individuals' BMI decreased by 0.05 kg/m ( = 0.06). As network exposure to overweight/obesity among friends increased, individuals' BMI significantly decreased by 0.06 kg/m ( = 0.04). There was no significant relationship between BMI and network exposure to overweight/obesity among family members. In conclusion, among Baltimore public housing residents, a statistically significant, inverse association existed between individuals' BMI and overweight/obesity among friends in their social networks. Our results differ from relationships seen in prior studies of other populations, which may be due to racial and/or contextual differences between studies.
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http://dx.doi.org/10.1016/j.pmedr.2019.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378834PMC
June 2019

Quality and Experience of Outpatient Care in the United States for Adults With or Without Primary Care.

JAMA Intern Med 2019 03;179(3):363-372

Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Importance: The US health care system is typically organized around hospitals and specialty care. The value of primary care remains unclear and debated.

Objective: To determine whether an association exists between receipt of primary care and high-value services, low-value services, and patient experience.

Design, Setting, And Participants: This is a nationally representative analysis of noninstitutionalized US adults 18 years or older who participated in the Medical Expenditure Panel Survey. Propensity score-weighted quality and experience of care were compared between 49 286 US adults with and 21 133 adults without primary care from 2012 to 2014. Temporal trends were also analyzed from 2002 to 2014.

Exposures: Patient-reported receipt of primary care, determined by the 4 "Cs" of primary care: first-contact care that is comprehensive, continuous, and coordinated.

Main Outcomes And Measures: Thirty-nine clinical quality measures and 7 patient experience measures aggregated into 10 clinical quality composites (6 high-value and 4 low-value services), an overall patient experience rating, and 2 experience composites.

Results: From 2002 to 2014, the mean annual survey response rate was 58% (range, 49%-65%). Between 2012 and 2014, compared with respondents without primary care (before adjustment), those with primary care were older (50 [95% CI, 50-51] vs 38 [95% CI, 38-39] years old), more often female (55% [95% CI, 54%-55%] vs 42% [95% CI, 41%-43%]), and predominately white individuals (50% [95% CI, 49%-52%] vs 43% [95% CI, 41%-45%]). After propensity score weighting, US adults with or without primary care had the same mean numbers of outpatient (6.7 vs 5.9; difference, 0.8 [95% CI, -0.2 to 1.8]; P = .11), emergency department (0.2 for both; difference, 0.0 [95% CI, -0.1 to 0.0]; P = .17), and inpatient (0.1 for both; difference, 0.0 [95% CI, 0.0-0.0]; P = .92) encounters annually, but those with primary care filled more prescriptions (mean, 14.1 vs 10.7; difference, 3.4 [95% CI, 2.0-4.7]; P < .001) and were more likely to have a routine preventive visit in the past year (mean, 72.2% vs 57.5%; difference, 14.7% [95% CI, 12.3%-17.1%]; P < .001). From 2012 to 2014, Americans with primary care received more high-value care in 4 of 5 composites. For example, 78% of those with primary care received high-value cancer screening compared with 67% without primary care (difference, 10.8% [95% CI, 8.5%-13.0%]; P < .001). Americans with or without primary care received low-value care with similar frequencies on 3 of 4 composites, although Americans with primary care received more low-value antibiotics (59% vs 48%; difference, 11.0% [95% CI, 2.8%-19.3%] P < .001). Respondents with primary care also reported significantly better health care access and experience. For example, physician communication was highly rated for a greater proportion of those with (64%) vs without (54%) primary care (difference, 10.2%; 95% CI, 7.2%-13.1%; P < .001). Differences in quality and experience between Americans with or without primary care were essentially stable between 2002 and 2014.

Conclusions And Relevance: Receipt of primary care was associated with significantly more high-value care, slightly more low-value care, and better health care experience. Policymakers and health system leaders seeking to improve value should consider increasing investments in primary care.
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http://dx.doi.org/10.1001/jamainternmed.2018.6716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439688PMC
March 2019

Discovery of common and rare genetic risk variants for colorectal cancer.

Nat Genet 2019 01 3;51(1):76-87. Epub 2018 Dec 3.

Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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http://dx.doi.org/10.1038/s41588-018-0286-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358437PMC
January 2019
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