Faculty Bibliography

BACKGROUND: The optimal dose for office-based buprenorphine therapy is not known. This study reports on the effect of a change in payer policy, in which the insurer of a subset of patients in an office-based practice imposed a maximum sublingual buprenorphine dose of 16 mg/day, thereby forcing those patients on higher daily doses to decrease their dose. This situation created conditions for a natural experiment, in which treatment outcomes for patients experiencing this dose decrease could be compared to patients with other insurance who were not challenged with a dose decrease. METHODS: Subjects were 297 patients with opioid use disorder in a primary care practice who were prescribed buprenorphine continuously for at least 3 months. Medical records were retrospectively reviewed for urine drug test results and treatment retention. Rates of aberrant urine drug tests were calculated in the period before the dose decrease and compared to rate after it with patients serving as their own controls. Comparison groups were formed from patients with the same insurance on buprenorphine doses of 16 mg/day or lower, patients with different insurance on 16 mg/day or lower, and patients with different insurance on greater than 16 mg/day. Rates of aberrant drug tests and treatment retention of patients on 16 mg/day or less of buprenorphine were compared to that of patients on higher daily doses. RESULTS: The rate of aberrant urine drug tests among patients who experienced a dose decrease rose from 27.5% to 34.2% (p=0.043). No comparison group showed any significant change in aberrant drug test rates. Moreover, all groups who were prescribed buprenorphine doses greater than 16 mg/day displayed lower rates of aberrant urine drug tests than groups prescribed lower doses. Retention in treatment was also highest among those prescribed greater than 16 mg/day (100% vs. 86.8%, 90.1%, and 84.4% p=0.010). DISCUSSION: An imposed buprenorphine dose decrease was associated with an increase in aberrant drug tests. Patients in a control group with higher buprenorphine doses had greater retention in treatment. These findings suggest that buprenorphine doses greater than 16 mg/day are more effective for some patients and that dose limits at this level or lower are harmful.

Incidental and secondary findings have become an important by-product of diagnostic testing, and their ramifications affect clinical care, research, and policy. Given parallels in the reporting and management of such findings on diagnostic imaging, radiologists may draw from ongoing discussions in medical genetics to rethink more patient-centered approaches to analogous clinical, ethical, and medicolegal dilemmas. Low-risk incidental findings in particular may be drivers of unnecessary testing, invasive procedures, and overtreatment, with associated financial, psychological, and clinical consequences. As radiologists act in patients' best interests by strengthening standardized guidelines on how each finding merits further diagnostic testing or treatment, perhaps the greatest challenge for producing such guidelines is for low-risk incidental findings, for which adverse consequences are unlikely but associated with substantial uncertainty because of the lack of strong evidence on which to base the recommendations. More uniform recommendations for managing low-risk radiologic incidental findings should therefore aim to provide reasonable options that apply across a spectrum of patient preferences. These will require evaluation through research and will ultimately influence the quality of care. Specific areas for exploration may include (1) better gauging of patient attitudes and preferences regarding low-risk incidental findings, (2) using patient preferences to inform more uniform recommendations for low-risk findings that apply across a spectrum of preferences and help guide shared decision making, and (3) when patients endorse a strong preference not to discover low-risk incidental findings, how it might be possible for professional standards to curtail their generation in specific circumstances.

AIMS: The present study assessed the longitudinal association of an elevated 1-h plasma glucose [1-h-PG >8.6mmol/l (155mg/dl)] with and without impaired glucose tolerance [IGT; 2-h-PG 7.8-11.0mmol/l (140-199mg/dl)] with cumulative incident of diabetes and prediabetes over 25years in a non-diabetic cohort. METHODS: From 1979 to 1984, 1970 non-diabetic men and women completed an oral glucose tolerance test (OGTT), physical and biochemical measurements as well as a questionnaire related to lifestyle and medical background. During the years 2000-2004, 853 survivors of the original cohort were interviewed and re-examined for glycemic progression. RESULTS: Individuals with 1-h-PG >8.6mmol/l (155mg/dl) but with 2-h-PG <7.8mmol/l (140mg/dl) had a significantly elevated risk, compared to those with both 1-h-PG 8.6mmol/l (155mg/dl) and 2-h-PG <7.8mmol/l (140mg/dl), for both diabetes [OR:4.35 (95%CI: 2.50-7.73)] and prediabetes outcomes [OR:1.87 (95%CI 1.09-3.26)], adjusted for sex and age, smoking, body mass index, blood pressure, fasting blood glucose and insulin. CONCLUSIONS: The risk for diabetes associated with a 1-h level >8.6mmol/l (155mg/dl) is increased and further worsened in the presence of IGT. Identifying individuals at risk with a 1-h-PG glucose level during an OGTT is recommended.

BACKGROUND: Little is known about the optimal use of shared decision making (SDM) to guide palliative and end-of-life decisions in the emergency department (ED). OBJECTIVE: To convene a working group to develop a set of research questions that, when answered, will substantially advance the ability of clinicians to use SDM to guide palliative and end-of-life care decisions in the ED. METHODS: Participants were identified based on expertise in emergency, palliative, or geriatrics care, policy, or patient-advocacy and spanned physician, nursing, social work, legal, and patient perspectives. Input from the group was elicited using a time-staggered Delphi process including three teleconferences, an open platform for asynchronous input, and an in-person meeting to obtain a final round of input from all members and to identify and resolve or describe areas of disagreement. CONCLUSION: Key research questions identified by the group related to which ED patients are likely to benefit from palliative care, what interventions can most effectively promote palliative care in the ED, what outcomes are most appropriate to assess the impact of these interventions, what is the potential for initiating advance care planning in the ED to help patients define long-term goals of care, and what policies influence palliative and end-of-life care decision making in the ED. Answers to these questions have the potential to substantially improve the quality of care for ED patients with advanced illness

BACKGROUND: Hepatitis C virus (HCV) infection causes significant morbidity and mortality among people who inject drugs (PWID) and HIV+ men who have sex with men (MSM). Characterizing spontaneous viral clearance of HCV infection among PWID and HIV+ MSM is important for assessing the burden of disease and treatment strategies in these populations. METHODS: Electronic and other searches of medical literature were conducted. Reports were eligible if they presented original data from upper-middle- and high-income countries on laboratory-confirmed HCV infection and spontaneous viral clearance among PWID or HIV+ MSM. Pooled estimates of spontaneous viral clearance were generated using fixed-effect and random-effects models. Meta-regression examined potential predictors related to individual characteristics and research methodology. RESULTS: The meta-analysis estimated that spontaneous viral clearance occurs in 24.4 % of PWID and 15.4 % of HIV+ MSM. In univariate meta-regression among PWID, male sex and age were significantly associated with spontaneous viral clearance, and in multivariate analysis, male sex and HIV positivity were predictors of spontaneous viral clearance; among HIV+ MSM no variables were found to affect spontaneous viral clearance. CONCLUSION: The variability in estimates of spontaneous viral clearance between HIV+ MSM and PWID suggests the impact of HIV co-infection and HCV re-infection. Due to limited data on additional factors that may affect the natural history of HCV, more research is needed to further understand spontaneous viral clearance in these risk groups. PROTOCOL REGISTRATION: The protocols for the PWID and HIV+ MSM research were registered with PROSPERO (CRD42014008805; CRD42013006462).

Networks inference problems are commonly found in multiple biomedical subfields such as genomics, metagenomics, neuroscience, and epidemiology. Networks are useful for representing a wide range of complex interactions ranging from those between molecular biomarkers, neurons, microbial communities, to those found in human or animal populations. Recent technological advances have resulted in an increasing amount of healthcare data in multiple modalities, increasing the preponderance of network inference problems. Multi-domain data can now be used to improve the robustness and reliability of recovered networks from unimodal data. For infectious diseases in particular, there is a body of knowledge that has been focused on combining multiple pieces of linked information. Combining or analyzing disparate modalities in concert has demonstrated greater insight into disease transmission than could be obtained from any single modality in isolation. This has been particularly helpful in understanding incidence and transmission at early stages of infections that have pandemic potential. Novel pieces of linked information in the form of spatial, temporal, and other covariates including high-throughput sequence data, clinical visits, social network information, pharmaceutical prescriptions, and clinical symptoms (reported as free-text data) also encourage further investigation of these methods. The purpose of this review is to provide an in-depth analysis of multimodal infectious disease transmission network inference methods with a specific focus on Bayesian inference. We focus on analytical Bayesian inference-based methods as this enables recovering multiple parameters simultaneously, for example, not just the disease transmission network, but also parameters of epidemic dynamics. Our review studies their assumptions, key inference parameters and limitations, and ultimately provides insights about improving future network inference methods in multiple applications.

INTRODUCTION: There has been a sharp decline in adolescents who smoke cigarettes but no national-level study evaluating the impact of smoking cessation counseling by pediatricians or other clinicians who care for children. METHODS: Combined data from ambulatory portions of the National Hospital Ambulatory Care Survey and National Ambulatory Medical Care Survey from 1997-1999 and 2009-2011 were analyzed to determine changes in the frequency of pediatric visits that included clinician-reported tobacco counseling and how such counseling varied by child, family, and clinician characteristics. RESULTS: In 1997-1999, 1.5% of all medical visits for children aged below 19 years included tobacco counseling; this increased to 3.8% in 2009-2011 (P < .001). A marked increase from 4.1% to 11.1% was noted at well-child visits (P < .001). There were significant increases in counseling by pediatricians but not mid-level providers or general/family physicians. Provision of counseling did not result in greater visit length during either time point. During 2009-2011, visits with a diagnosis of asthma were four times as likely (OR 4.2, 95% CI 2.8-6.2) and visits for otitis media two times as likely (OR 2.1, 95% CI 1.2-3.7) to include smoking cessation counseling than sick visits for all other diagnoses. CONCLUSION: These results demonstrate a significant increase in tobacco counseling by pediatric providers within the last decade, especially at well-child visits. However, the American Academy of Pediatrics' recommendation that pediatricians counsel about the harms of tobacco use and secondhand smoke exposure has not yet been exhaustively implemented. IMPLICATIONS: A significant increase in smoking cessation counseling at pediatric medical appointments, especially at well-child visits, occurred from 2009-2011 compared with 1997-1999, paralleling a large decrease in smoking prevalence. These improvements in counseling rates have been predominantly noted for pediatricians but not mid-level providers or general practitioners. Counseling was not associated with increased visit lengths. Although improved counseling practices by pediatricians have been demonstrated, there is still room for improvement.

We investigated the contribution of preschoolers' executive function (EF) skills to the effectiveness of their spontaneous strategy production when learning. Performance on computerized tasks of inhibition, attention shifting, and working memory was examined in relation to the effectiveness of 112 3- to 5-year-olds' spontaneous strategy production on a spatial memory task. Participants were asked to remember the locations of four toys representing one of two categories (animals or chairs) placed in a wooden box. Most participants spontaneously implemented a clustering strategy by removing and/or replacing the toys according to category membership. However, less than half of these strategic participants showed concomitant memory benefits (recall of toy locations). The remainder showed a utilization deficiency. After controlling for age and IQ, participants who performed better on EF tasks were more likely to benefit from having used the clustering strategy. These findings indicate that utilization deficiencies among preschoolers may be partially accounted for by individual differences in EF.

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10-15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10-9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10-8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10-8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10-4-2.0x10-3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Opioid overdose prevention is a pressing public health concern and intranasal naloxone rescue kits are a useful tool in preventing fatal overdose. We evaluated the attitudes, knowledge, and experiences of patients and providers related to overdose and naloxone rescue. Over a six month period, patients and providers within a large community hospital in Staten Island were recruited to complete tailored questionnaires for their respective groupings. 100 patients and 101 providers completed questionnaires between August, 2014 and January, 2015. Patient participants were primarily Caucasian males with a mean age of 37.7 years, of which 65% accurately identified naloxone for opioid overdose, but only 21% knew more specific clinical features. 68% of patients had previously witnessed a drug overdose. Notably, 58% of patients anticipated their behavior would change if provided access to an intranasal naloxone rescue kit, of which 83% predicted an increase in opioid use. Prior overdose was significantly correlated with anticipating no change in subsequent opioid use pattern (p=0.02). 99% of patients reported that their rapport with their health-care provider would be enhanced if offered an intranasal naloxone rescue kit. As for providers, 24% had completed naloxone rescue kit training, and 96% were able to properly identify its clinical application. 50% of providers felt naloxone access would decrease the likelihood of an overdose occurring, and 58% felt it would not contribute to high-risk behavior. Among providers, completion of naloxone training was correlated with increased awareness of where to access kits for patients (p<0.001). This study suggests that patients and providers have distinct beliefs and attitudes toward overdose prevention. Patient-Provider discussion of overdose prevention enhances patients' rapport with providers. However, access to an intranasal naloxone rescue kit may make some patients more vulnerable to high-risk behavior. Future research efforts examining provider and patient beliefs and practices are needed to help develop and implement effective hospital-based opioid overdose prevention strategies.