Decoding Genetics, Ancestry, and Geospatial Context for Precision Health.

Mass General Brigham, an integrated healthcare system based in the Greater Boston area of Massachusetts, annually serves 1.5 million patients. We established the Mass General Brigham Biobank (MGBB), encompassing 142,238 participants, to unravel the intricate relationships among genomic profiles, environmental context, and disease manifestations within clinical practice. In this study, we highlight the impact of ancestral diversity in the MGBB by employing population genetics, geospatial assessment, and association analyses of rare and common genetic variants. The population structures captured by the genetics mirror the sequential immigration to the Greater Boston area throughout American history, highlighting communities tied to shared genetic and environmental factors. Our investigation underscores the potency of unbiased, large-scale analyses in a healthcare-affiliated biobank, elucidating the dynamic interplay across genetics, immigration, structural geospatial factors, and health outcomes in one of the earliest American sites of European colonization.

Antithrombin III supplementation during neonatal and pediatric extracorporeal membrane oxygenation.

BACKGROUND: Bleeding and thrombosis are common extracorporeal membrane oxygenation (ECMO) complications associated with increased mortality. Heparin is the most commonly used ECMO anticoagulant, employed in 94% of cases. Reduced antithrombin III (AT3) levels could decrease heparin effectiveness. Neonates have inherently lower levels of AT3 than adults, and pediatric patients on ECMO can develop AT3 deficiency. One potential approach for patients on ECMO with AT3 deficiency is exogenous AT3 supplementation. However, there is conflicting data concerning the use of AT3 for pediatric and neonatal patients on ECMO. METHODS: We analyzed the Bleeding and Thrombosis during ECMO database of 514 neonatal and pediatric patients on ECMO. We constructed daily regression models to determine the association between AT3 supplementation and rates of bleeding and thrombosis. Given the physiological differences between pediatric patients and neonates, we constructed separate models for each. RESULTS: AT3 administration was associated with increased rates of daily bleeding among pediatric (adjusted odds ratio [aOR] 1.59, p < 0.01) and neonatal (aOR 1.37, p = 0.04) patients. AT3 supplementation did not reduce the rate of thrombosis for either pediatric or neonatal patients. CONCLUSION: AT3 administration was associated with increased rates of daily bleeding, a hypothesized potential complication of AT3 supplementation. In addition, AT3 supplementation did not result in lower rates of thrombosis. We recommend clinicians utilize caution when considering supplementing patients on ECMO with exogenous AT3.

Observation and Patients' Perceptions of Incorporating Their Photograph Into the Electronic Health Record.

OBJECTIVES: Wrong-patient errors are common and have the potential to cause serious harm. The Office of the National Coordinator for Health Information Technology Patient Identification SAFER Guide recommends displaying patient photographs in electronic health record (EHR) systems to facilitate patient identification and reduce wrong-patient errors. A potential barrier to implementation is patient refusal; however, patients' perceptions about having their photograph captured during registration and integrated into the EHR are unknown. METHODS: The study was conducted in an emergency department (ED) and primary care outpatient clinic within a large integrated health system in New York City. The study consisted of 2 components: (1) direct observation of the registration process to quantify the frequency of patient refusals and (2) semistructured interviews to elicit patients' feedback on perceived benefits and barriers to integrating their photograph into the EHR. RESULTS: Of 172 registrations where patients were asked to take a photograph for patient identification, 0 refusals were observed (ED, 0 of 87; primary care outpatient clinic, 0 of 85). A convenience sample of 30 patients were interviewed (female, 70%; age ≥55 years, 43%; Hispanic/Latino, 67%; Black, 23%). Perceived benefits of integrating patient photographs into the EHR included improved security (40%), improved patient identification (23%), and ease of registration (17%). A small proportion of patients raised privacy concerns. CONCLUSIONS: Patient refusal was not found to be a barrier to implementation of patient photographs in the EHR. Efforts to identify and address other potential barriers would help ensure that the highest proportion of patients has photographs in their medical record.

A Randomized-Controlled Trial of Mentalization-Based Treatment Compared With Structured Case Management for Borderline Personality Disorder in a Mainstream Public Health Service.

Background: Treatment of borderline personality disorder (BPD) in publicly funded mental health services generally use approaches based on medical interventions and generic case management. Specific psychological therapies developed for BPD may be more effective but have rarely been evaluated in routine clinical practice. Aim: To examine the effectiveness of Mentalization Based Treatment (MBT) in adults with an established diagnosis of BPD under the care of a publicly funded Mental Health Service (MHS), on rates of non-suicidal self-harm (NSSH) and attempted suicide (SA). Methods: A randomized, controlled trial (RCT) comparing 18 months of MBT with Enhanced Therapeutic Case Management (ETCM), a form of Structured Clinical Case Management (ICTRP: ACTRN12612000951853). Participants were adults recruited from a patient population under the care of a publicly funded mental health service (MHS) with a confirmed diagnosis of BPD. The primary outcome measures were the incidence of non-suicidal self-harm or suicide attempt over 18 months of treatment. Results: 72 participants (71 females, 1 male) were randomized to MBT (n = 38) or ETCM (n = 34). Both groups showed a significant reduction in the overall incident rate of SA and NSSH. Between groups, SA rates were higher in the MBT group and conversely NSSH rates were higher in the ECTM group. Conclusions: The introduction of a structured service that delivered a structured psychotherapy (MBT) and an effective case management approach (ETCM) both resulted in a reduction in SA and NSSH. The differences in improvements found between groups within this study setting will require further research.

California's methane super-emitters.

Methane is a powerful greenhouse gas and is targeted for emissions mitigation by the US state of California and other jurisdictions worldwide1,2. Unique opportunities for mitigation are presented by point-source emitters-surface features or infrastructure components that are typically less than 10 metres in diameter and emit plumes of highly concentrated methane3. However, data on point-source emissions are sparse and typically lack sufficient spatial and temporal resolution to guide their mitigation and to accurately assess their magnitude4. Here we survey more than 272,000 infrastructure elements in California using an airborne imaging spectrometer that can rapidly map methane plumes5-7. We conduct five campaigns over several months from 2016 to 2018, spanning the oil and gas, manure-management and waste-management sectors, resulting in the detection, geolocation and quantification of emissions from 564 strong methane point sources. Our remote sensing approach enables the rapid and repeated assessment of large areas at high spatial resolution for a poorly characterized population of methane emitters that often appear intermittently and stochastically. We estimate net methane point-source emissions in California to be 0.618 teragrams per year (95 per cent confidence interval 0.523-0.725), equivalent to 34-46 per cent of the state's methane inventory8 for 2016. Methane 'super-emitter' activity occurs in every sector surveyed, with 10 per cent of point sources contributing roughly 60 per cent of point-source emissions-consistent with a study of the US Four Corners region that had a different sectoral mix9. The largest methane emitters in California are a subset of landfills, which exhibit persistent anomalous activity. Methane point-source emissions in California are dominated by landfills (41 per cent), followed by dairies (26 per cent) and the oil and gas sector (26 per cent). Our data have enabled the identification of the 0.2 per cent of California's infrastructure that is responsible for these emissions. Sharing these data with collaborating infrastructure operators has led to the mitigation of anomalous methane-emission activity10.

Risk of Wrong-Patient Orders Among Multiple vs Singleton Births in the Neonatal Intensive Care Units of 2 Integrated Health Care Systems.

IMPORTANCE: Multiple-birth infants in neonatal intensive care units (NICUs) have nearly identical patient identifiers and may be at greater risk of wrong-patient order errors compared with singleton-birth infants. OBJECTIVES: To assess the risk of wrong-patient orders among multiple-birth infants and singletons receiving care in the NICU and to examine the proportion of wrong-patient orders between multiple-birth infants and siblings (intrafamilial errors) and between multiple-birth infants and nonsiblings (extrafamilial errors). DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted in 6 NICUs of 2 large, integrated health care systems in New York City that used distinct temporary names for newborns per the requirements of The Joint Commission. Data were collected from 4 NICUs at New York-Presbyterian Hospital from January 1, 2012, to December 31, 2015, and 2 NICUs at Montefiore Health System from July 1, 2013, to June 30, 2015. Data were analyzed from May 1, 2017, to December 31, 2017. All infants in the 6 NICUs for whom electronic orders were placed during the study periods were included. MAIN OUTCOMES AND MEASURES: Wrong-patient electronic orders were identified using the Wrong-Patient Retract-and-Reorder (RAR) Measure. This measure was used to detect RAR events, which are defined as 1 or more orders placed for a patient that are retracted (ie, canceled) by the same clinician within 10 minutes, then reordered by the same clinician for a different patient within the next 10 minutes. RESULTS: A total of 10 819 infants were included: 85.5% were singleton-birth infants and 14.5% were multiple-birth infants (male, 55.8%; female, 44.2%). The overall wrong-patient order rate was significantly higher among multiple-birth infants than among singleton-birth infants (66.0 vs 41.7 RAR events per 100 000 orders, respectively; adjusted odds ratio, 1.75; 95% CI, 1.39-2.20; P < .001). The rate of extrafamilial RAR events among multiple-birth infants (36.1 per 100 000 orders) was similar to that of singleton-birth infants (41.7 per 100 000 orders). The excess risk among multiple-birth infants (29.9 per 100 000 orders) appears to be owing to intrafamilial RAR events. The risk increased as the number of siblings receiving care in the NICU increased; a wrong-patient order error occurred in 1 in 7 sets of twin births and in 1 in 3 sets of higher-order multiple births. CONCLUSIONS AND RELEVANCE: This study suggests that multiple-birth status in the NICU is associated with significantly increased risk of wrong-patient orders compared with singleton-birth status. This excess risk appears to be owing to misidentification between siblings. These results suggest that a distinct naming convention as required by The Joint Commission may provide insufficient protection against identification errors among multiple-birth infants. Strategies to reduce this risk include using given names at birth, changing from temporary to given names when available, and encouraging parents to select names for multiple births before they are born when acceptable to families.

Effect of Restriction of the Number of Concurrently Open Records in an Electronic Health Record on Wrong-Patient Order Errors: A Randomized Clinical Trial.

Importance: Recommendations in the United States suggest limiting the number of patient records displayed in an electronic health record (EHR) to 1 at a time, although little evidence supports this recommendation. Objective: To assess the risk of wrong-patient orders in an EHR configuration limiting clinicians to 1 record vs allowing up to 4 records opened concurrently. Design, Setting, and Participants: This randomized clinical trial included 3356 clinicians at a large health system in New York and was conducted from October 2015 to April 2017 in emergency department, inpatient, and outpatient settings. Interventions: Clinicians were randomly assigned in a 1:1 ratio to an EHR configuration limiting to 1 patient record open at a time (restricted; n = 1669) or allowing up to 4 records open concurrently (unrestricted; n = 1687). Main Outcomes and Measures: The unit of analysis was the order session, a series of orders placed by a clinician for a single patient. The primary outcome was order sessions that included 1 or more wrong-patient orders identified by the Wrong-Patient Retract-and-Reorder measure (an electronic query that identifies orders placed for a patient, retracted, and then reordered shortly thereafter by the same clinician for a different patient). Results: Among the 3356 clinicians who were randomized (mean [SD] age, 43.1 [12.5] years; mean [SD] experience at study site, 6.5 [6.0] years; 1894 females [56.4%]), all provided order data and were included in the analysis. The study included 12 140 298 orders, in 4 486 631 order sessions, placed for 543 490 patients. There was no significant difference in wrong-patient order sessions per 100 000 in the restricted vs unrestricted group, respectively, overall (90.7 vs 88.0; odds ratio [OR], 1.03 [95% CI, 0.90-1.20]; P = .60) or in any setting (ED: 157.8 vs 161.3, OR, 1.00 [95% CI, 0.83-1.20], P = .96; inpatient: 185.6 vs 185.1, OR, 0.99 [95% CI, 0.89-1.11]; P = .86; or outpatient: 7.9 vs 8.2, OR, 0.94 [95% CI, 0.70-1.28], P = .71). The effect did not differ among settings (P for interaction = .99). In the unrestricted group overall, 66.2% of the order sessions were completed with 1 record open, including 34.5% of ED, 53.7% of inpatient, and 83.4% of outpatient order sessions. Conclusions and Relevance: A strategy that limited clinicians to 1 EHR patient record open compared with a strategy that allowed up to 4 records open concurrently did not reduce the proportion of wrong-patient order errors. However, clinicians in the unrestricted group placed most orders with a single record open, limiting the power of the study to determine whether reducing the number of records open when placing orders reduces the risk of wrong-patient order errors. Trial Registration: clinicaltrials.gov Identifier: NCT02876588.

Personal Genomic Testing for Cancer Risk: Results From the Impact of Personal Genomics Study.

Purpose Significant concerns exist regarding the potential for unwarranted behavior changes and the overuse of health care resources in response to direct-to-consumer personal genomic testing (PGT). However, little is known about customers' behaviors after PGT. Methods Longitudinal surveys were given to new customers of 23andMe (Mountain View, CA) and Pathway Genomics (San Diego, CA). Survey data were linked to individual-level PGT results through a secure data transfer process. Results Of the 1,042 customers who completed baseline and 6-month surveys (response rate, 71.2%), 762 had complete cancer-related data and were analyzed. Most customers reported that learning about their genetic risk of cancers was a motivation for testing (colorectal, 88%; prostate, 95%; breast, 94%). No customers tested positive for pathogenic mutations in highly penetrant cancer susceptibility genes. A minority of individuals received elevated single nucleotide polymorphism-based PGT cancer risk estimates (colorectal, 24%; prostate, 24%; breast, 12%). At 6 months, customers who received elevated PGT cancer risk estimates were not significantly more likely to change their diet, exercise, or advanced planning behaviors or engage in cancer screening, compared with individuals at average or reduced risk. Men who received elevated PGT prostate cancer risk estimates changed their vitamin and supplement use more than those at average or reduced risk (22% v 7.6%, respectively; adjusted odds ratio, 3.41; 95% CI, 1.44 to 8.18). Predictors of 6-month behavior include baseline behavior (exercise, vitamin or supplement use, and screening), worse health status (diet and vitamin or supplement use), and older age (advanced planning, screening). Conclusion Most adults receiving elevated direct-to-consumer PGT single nucleotide polymorphism-based cancer risk estimates did not significantly change their diet, exercise, advanced care planning, or cancer screening behaviors.

A case of commotio cordis treated with therapeutic hypothermia.

BACKGROUND: Therapeutic hypothermia is used as a neuroprotective strategy for patients who have persistent neurologic compromise after return of spontaneous circulation from cardiac arrest. The 2010 American Heart Association Guidelines recommend the use of therapeutic hypothermia in adult cardiac arrest patients when the initial rhythm is ventricular fibrillation. These recommendations are based on primary research in patients with a cardiac cause of their ventricular fibrillation. CASE REPORT: A 43-year-old male was brought to our emergency department (ED) with commotio cordis. He was struck in the chest with a baseball bat, after which he collapsed at the scene and was pulseless. Return of spontaneous circulation was achieved after defibrillation by treating paramedics, and the patient remained comatose on arrival to the ED. He was transferred to the intensive care unit and treated with therapeutic hypothermia at target temperature of 32-34°C. He was extubated on day 3, and discharged home on day 8 with good neurologic function. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We report a case of commotio cordis in which the adult patient was treated with therapeutic hypothermia and had a favorable outcome. To our knowledge, this is the first reported case of its kind. Evidence for the use of therapeutic hypothermia is incomplete in patients with a traumatic cause of cardiac arrest, such as commotio cordis, despite probable similarities in the pathophysiology of anoxic brain injury. Our case illustrates that there may be benefit from use of therapeutic hypothermia for a broader population than is currently recommended.

Effect of Alzheimer disease genetic risk disclosure on dietary supplement use.

BACKGROUND: Genetic susceptibility testing for Alzheimer disease (AD) with APOE genotype disclosure is not recommended for clinical use but is available through direct-to-consumer (DTC) genetic testing companies. Little is known about whether APOE genotype disclosure would actually prompt changes in nutrition behaviors among at-risk individuals. OBJECTIVE: We studied the effect of APOE genotype disclosure for AD risk assessment on dietary supplement use in adults with a family history of AD. DESIGN: As part of a secondary analysis of data from the second Risk Evaluation and Education for Alzheimer's Disease Study, we examined the effect of genotype disclosure on health-behavior changes among 272 unaffected first-degree relatives of persons with AD. RESULTS: Overall, 16% of all participants reported a change in dietary supplement use after AD risk assessment. Participants who learned that they had at least one copy of the risk-increasing epsilon4 allele (epsilon4+) had 4.75 times the odds of reporting a change in dietary supplement use than did their counterparts who had an absence of the risk-increasing epsilon4 allele (epsilon4-) (95% CI: 2.23, 10.10; P < 0.0001) after adjustment for age, sex, race, baseline supplement use, randomization arm, and educational level. There were no significant differences between APOE epsilon4+ and epsilon4- participants in changes in overall diet, exercise, or medications. CONCLUSIONS: In this sample of first-degree relatives receiving genetic susceptibility testing for AD, an APOE epsilon4+ genotype status was positively associated with dietary supplement use after risk disclosure. Such changes occurred despite the absence of evidence that supplement use reduces the risk of AD. Given the expansion of DTC genetic tests, this study highlights the need for future studies in disease risk communication.

Acute toxicity evaluation of proliferol: a dose-escalating, placebo-controlled study in swine.

Prolotherapy is one of the many treatments available for chronic musculoskeletal disorders. A commonly used drug contains dextrose 12.5%, glycerin 12.5%, phenol 1.0%, and lidocaine hydrochloride 0.25% in aqueous solution (recently termed Proliferol). For chronic low back pain, this is injected into lumbosacral ligaments to stimulate connective tissue repair. Despite generally positive clinical results, the toxicity of this drug is not well characterized and was assessed in 48 (24 male, 24 female) Yucatan miniature swine randomly assigned to low (1x), medium (5x), or high (10x) dose or saline placebo. Outcomes included clinical observations, clinical chemistry, hematology, coagulation, urinalysis, toxicokinetics, and full gross and microscopic histopathology after 24 hours or 14 days. Findings attributable to Proliferol after 24 hours included dose-response elevations in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase, which returned to normal after 14 days. There were no remarkable findings in hematology, coagulation, or urinalysis. Urine concentrations of lidocaine and phenol both peaked after 8 hours. Histopathology findings after 24 hours included hemorrhage, inflammation, necrosis, and vascular changes in the ligaments and adjacent soft tissues at the sites of injection. After 14 days, there was evidence of repair under way, with fibrosis and skeletal muscle regeneration at the injection sites.

Vitamin A supplementation ameliorates butyric acid-induced intestinal mucosal injury in newborn rats.

Vitamin A (vit A) plays an important role in wound healing and therefore may help in repairing of intestinal mucosal injury. The purpose of this study was to determine if vit A supplementation could promote healing in intestinal mucosal injury as commonly seen in neonatal necrotizing enterocolitis (NEC). Mild intestinal mucosal injury was induced in 10-day-old Sprague-Dawley rats by luminal administration of 1.5% butyric acid (BA) at pH 4.0. Normal saline at the same pH was administered as control. Immediately after administrations of BA or normal saline, animals were randomly assigned to receive high dose vit A (20,000 IU/kg for one dose, i.p.), low dose vit A (5,000 IU/kg for two doses) or vehicle. Animals were followed for 48 hours and then sacrificed for histological examination. Rats with BA-induced intestinal mucosal injury had a reduction in daily weight gain (p < 0.05). Vit A supplementation significantly improved the daily weight gain in the rats with BA-induced intestinal mucosal injury and the effect is dose dependent. At sacrifice, the colon wet weight was significantly heavier and the histological injury scores from both ileum and proximal colon higher in the rats with BA-induced intestinal mucosal injury. All of those parameters were improved with vit A supplementation. We conclude that vit A supplementation ameliorates BA induced-intestinal mucosal injury in newborn rats.

Surveillance for second primary colorectal cancer after adjuvant chemotherapy: an analysis of Intergroup 0089.

BACKGROUND: The incidence of second primary colorectal cancer in patients with a history of colon cancer, compared with patients with a history of adenomatous polyps, is unknown. It is unclear whether guidelines for colonoscopy screening in patients with polyps are appropriate for patients with previous colon cancer. OBJECTIVE: To determine the incidence of second primary colorectal cancer after treatment for localized colon cancer and to compare this incidence with that of first primary colorectal cancer in both the general population and high-risk patients. DESIGN: Historical cohort study. SETTING: An international, multi-institutional trial of adjuvant 5-fluorouracil-based chemotherapy for localized colon cancer. PATIENTS: 3278 patients with resected stage II and stage III colon cancer. MEASUREMENTS: Occurrence of endoscopic or radiologic colon surveillance and incidence of second primary colorectal cancer. RESULTS: Forty-two cases of second primary invasive colon cancer were found over 15 345 person-years of follow-up, yielding an incidence rate of 274 per 100 000 person-years (95% CI, 196 to 369 per 100 000 person-years) and a cumulative incidence of 1.5% (CI, 1.1% to 2.0%) at 5 years. This rate was compared with rates of first colon cancer in two reference groups: the general population and patients who had undergone frequent colonoscopy and polypectomy because of a history of adenomatous polyps; standardized incidence ratios were 1.6 (CI, 1.2 to 2.2) and 6.8 (CI, 2.7 to 22.0), respectively. CONCLUSION: The incidence of second primary colorectal cancer remains high despite intensive surveillance strategies.