Faculty Bibliography

BACKGROUND:Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation. METHODS:To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2507 African American (AA) and European American (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study. To validate our findings, we assayed an additional 2528 participants from the Cardiovascular Health Study (CHS) (N = 533) and Framingham Heart Study (FHS) (N = 1995). We further assessed the effect of experimental modification of mtDNA-CN through knockout of TFAM, a regulator of mtDNA replication, via CRISPR-Cas9. RESULTS:) studies. CONCLUSIONS:These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential expression of specific genes that may impact human health and disease via altered cell signaling.

PURPOSE OF REVIEW/OBJECTIVE:This narrative review examines the use of behavioral interventions for acute treatment of headache and pain in the emergency department (ED)/urgent care (UC) and inpatient settings. RECENT FINDINGS/RESULTS:Behavioral interventions demonstrate reductions of pain and associated disability in headache, migraine, and other conditions in the outpatient setting. Behavioral treatments may be a useful addition for patients presenting with acute pain to hospitals and emergency departments. We review challenges and limitations and offer suggestions for implementation of behavioral interventions in the acute setting. Some evidence exists for relaxation-based treatments, mindfulness-based treatments, hypnosis/self-hypnosis, and immersive virtual reality for acute pain, migraine, and headache. There are few high-quality studies on behavioral treatments in the inpatient and emergency department settings. Further research is warranted to determine the efficacy and cost-effectiveness of these interventions. Given the general safety and cost-effectiveness of behavioral interventions, healthcare professionals may want to include these therapies in treatment plans.

INTRODUCTION/BACKGROUND:It is difficult to determine illness severity for coronavirus disease 2019 (COVID-19) patients, especially among stable-appearing emergency department (ED) patients. We evaluated patient outcomes among ED patients with a documented ambulatory oxygen saturation measurement. METHODS:This was a retrospective chart review of ED patients seen at New York University Langone Health during the peak of the COVID-19 pandemic in New York City. We identified ED patients who had a documented ambulatory oxygen saturation. We studied the outcomes of high oxygen requirement (defined as >4 liters per minute) and mechanical ventilation among admitted patients and bounceback admissions among discharged patients. We also performed logistic regression and compared the performance of different ambulatory oxygen saturation cutoffs in predicting these outcomes. RESULTS:Between March 15-April 14, 2020, 6194 patients presented with fever, cough, or shortness of breath at our EDs. Of these patients, 648 (11%) had a documented ambulatory oxygen saturation, of which 165 (24%) were admitted. Notably, admitted and discharged patients had similar initial vital signs. However, the average ambulatory oxygen saturation among admitted patients was significantly lower at 89% compared to 96% among discharged patients (p<0.01). Among admitted patients with an ambulatory oxygen saturation, 30% had high oxygen requirements and 8% required mechanical ventilation. These rates were predicted by low ambulatory oxygen saturation (p<0.01). Among discharged patients, 50 (10%) had a subsequent ED visit resulting in admission. Although bounceback admissions were predicted by ambulatory oxygen saturation at the first ED visit (p<0.01), our analysis of cutoffs suggested that this association may not be clinically useful. CONCLUSION/CONCLUSIONS:Measuring ambulatory oxygen saturation can help ED clinicians identify patients who may require high levels of oxygen or mechanical ventilation during admission. However, it is less useful for identifying which patients may deteriorate clinically in the days after ED discharge and require subsequent hospitalization.

Few studies have assessed the fidelity of practice facilitation (PF) as an implementation strategy, and none have used an a priori definition or conceptual framework of fidelity to guide fidelity assessment. The authors adapted the Conceptual Framework for Implementation Fidelity to guide fidelity assessment in HealthyHearts NYC, an intervention that used PF to improve adoption of cardiovascular disease evidence-based guidelines in primary care practices. Data from a web-based tracking system of 257 practices measured fidelity using 4 categories: frequency, duration, content, and coverage. Almost all (94.2%) practices received at least the required 13 PF visits. Facilitators spent on average 26.3 hours at each site. Most practices (95.7%) completed all Task List items, and 71.2% were educated on all Chronic Care Model strategies. The majority (65.8%) received full coverage. This study provides a model that practice managers and implementers can use to evaluate fidelity of PF, and potentially other implementation strategies.

Infant birth weight influences numerous health outcomes throughout the life course including childhood obesity and metabolic morbidities. Maternal experience of stress, both before and during pregnancy, has been hypothesized to influence fetal growth and birth outcomes. However, these associations currently are not fully understood, due to conflicting results in the published literature. Salivary cortisol is often used as a biological biomarker to assess the diurnal pattern of the hypothalamic-pituitary-adrenal axis (HPA-axis) functioning. Cortisol metrics include both the total cortisol concentration secreted during waking hours, reflected by the area under the curve (AUC), and cortisol dynamics, which include the diurnal cortisol slope (DCS) and the cortisol awakening response (CAR). This study examined the association of these cortisol metrics measured during the third trimester of pregnancy and infant birth weight among 240 mother-infant dyads participating in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort study, which is predominately comprised of Hispanic low-income women. There were no significant associations with the maternal biological stress response and infant birth weight in this study. More research is needed in larger studies to better understand how the biological stress response influences birth weight in populations facing health disparities.

OBJECTIVE:To identify county characteristics associated with high versus low well-being among high-poverty counties. DESIGN:Observational cross-sectional study at the county level to investigate the associations of 29 county characteristics with the odds of a high-poverty county reporting population well-being in the top quintile versus the bottom quintile of well-being in the USA. County characteristics representing key determinants of health were drawn from the Robert Wood Johnson Foundation County Health Rankings and Roadmaps population health model. SETTING:Counties in the USA that are in the highest quartile of poverty rate. MAIN OUTCOME MEASURE:Gallup-Sharecare Well-being Index, a comprehensive population-level measure of physical, mental and social health. Counties were classified as having a well-being index score in the top or bottom 20% of all counties in the USA. RESULTS:Among 770 high-poverty counties, 72 were categorised as having high well-being and 311 as having low well-being. The high-well-being counties had a mean well-being score of 71.8 with a SD of 2.3, while the low-well-being counties had a mean well-being score of 60.2 with a SD of 2.8. Among the six domains of well-being, basic access, which includes access to housing and healthcare, and life evaluation, which includes life satisfaction and optimism, differed the most between high-being and low-well-being counties. Among 29 county characteristics tested, six were independently and significantly associated with high well-being (p<0.05). These were lower rates of preventable hospital stays, higher supply of primary care physicians, lower prevalence of smoking, lower physical inactivity, higher percentage of some college education and higher percentage of heavy drinkers. CONCLUSIONS:Among 770 high-poverty counties, approximately 9% outperformed expectations, reporting a collective well-being score in the top 20% of all counties in the USA. High-poverty counties reporting high well-being differed from high-poverty counties reporting low well-being in several characteristics.

INTRODUCTION/BACKGROUND:Data regarding underpinning and implications of ethical challenges faced by humanitarian workers and their organisations in humanitarian operations are limited. METHODS:We conducted comprehensive, semistructured interviews with 44 experienced humanitarian aid workers, from the field to headquarters, to evaluate and describe ethical conditions in humanitarian situations. RESULTS:61% were female; average age was 41.8 years; 500 collective years of humanitarian experience (11.8 average) working with diverse major international non-governmental organisations. Important themes included; allocation schemes and integrity of the humanitarian industry, including resource allocation and fair access to and use of services; staff or organisational competencies and aid quality; humanitarian process and unintended consequences; corruption, diversion, complicity and competing interests, and intentions versus outcomes; professionalism and interpersonal and institutional responses; and exposure to extreme inequities and emotional and moral distress. Related concepts included broader industry context and allocations; decision-making, values, roles and sustainability; resource misuse at programme, government and international agency levels; aid effectiveness and utility versus futility, and negative consequences. Multiple contributing, confounding and contradictory factors were identified, including context complexity and multiple decision-making levels; limited input from beneficiaries of aid; different or competing social constructs, values or sociocultural differences; and shortcomings, impracticality, or competing philosophical theories or ethical frameworks. CONCLUSIONS:Ethical situations are overarching and often present themselves outside the exclusive scope of moral reasoning, philosophical views, professional codes, ethical or legal frameworks, humanitarian principles or social constructivism. This study helped identify a common instinct to uphold fairness and justice as an underlying drive to maintain humanity through proximity, solidarity, transparency and accountability.

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (+/- 500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn's disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P-values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (+/- 500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn's disease, and inflammatory bowel disease remained associated with PDAC (P-values = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P-value = 0.22) and primary sclerosing cholangitis (P-value = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn's disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC.

BACKGROUND:Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE:To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN:Individual participant-based meta-analysis. SETTING:12 research and 21 clinical cohorts. PARTICIPANTS:919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS:Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS:Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR. LIMITATION:Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample. CONCLUSION:Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis. PRIMARY FUNDING SOURCE:National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

CONTEXT/BACKGROUND:The first case of the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), was identified in Wuhan, China, in late 2019. Since then, the coronavirus disease 2019 (COVID-19) outbreak was reclassified as a pandemic, and health systems around the world have faced an unprecedented challenge. OBJECTIVE:To summarize guidelines and recommendations on the urology standard of care during the COVID-19 pandemic. EVIDENCE ACQUISITION/METHODS:Guidelines and recommendations published between November 2019 and April 17, 2020 were retrieved using MEDLINE, EMBASE, and CINAHL. This was supplemented by searching the web pages of international urology societies. Our inclusion criteria were guidelines, recommendations, or best practice statements by international urology organizations and reference centers about urological care in different phases of the COVID-19 pandemic. Our systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Of 366 titles identified, 15 guidelines met our criteria. EVIDENCE SYNTHESIS/RESULTS:Of the 15 guidelines, 14 addressed emergency situations and 12 reported on assessment of elective uro-oncology procedures. There was consensus on postponing radical prostatectomy except for high-risk prostate cancer, and delaying treatment for low-grade bladder cancer, small renal masses up to T2, and stage I seminoma. According to nine guidelines that addressed endourology, obstructed or infected kidneys should be decompressed, whereas nonobstructing stones and stent removal should be rescheduled. Five guidelines/recommendations discussed laparoscopic and robotic surgery, while the remaining recommendations focused on outpatient procedures and consultations. All recommendations represented expert opinions, with three specifically endorsed by professional societies. Only the European Association of Urology guidelines provided evidence-based levels of evidence (mostly level 3 evidence). CONCLUSIONS:To make informed decisions during the COVID-19 pandemic, there are multiple national and international guidelines and recommendations for urologists to prioritize the provision of care. Differences among the guidelines were minimal. PATIENT SUMMARY/UNASSIGNED:We performed a systematic review of published recommendations on urological practice during the coronavirus disease 2019 (COVID-19) pandemic, which provide guidance on prioritizing the timing for different types of urological care.