Faculty Bibliography

PURPOSE/OBJECTIVE:Active surveillance (AS) for intermediate-risk prostate cancer (PCa) is controversial. Many AS programs are limited to grade group (GG) 1 (Gleason 6) and PSA<10 ng/ml. However, recent guidelines state that AS can be considered for limited GG2 (Gleason 3+4), despite limited data on outcomes. Our objective was to compare prostatectomy outcomes between subgroups of intermediate-risk versus low-risk PCa. METHODS:We performed an observational study in the National Prostate Cancer Register (NPCR) of Sweden, including 98% of PCa nationwide. From 2009-2012, 5087 men with low-risk (GG1, PSA<10, and ≤cT2) and intermediate-risk PCa (GG2 or PSA 10-20, or T2) underwent radical prostatectomy. We compared upgrading and upstaging between groups, based on the UCSF Cancer of the Prostate Risk Assessment (CAPRA) scores and published AS criteria. Results were validated in an independent dataset of cases diagnosed 2013-2016. RESULTS:Men with GG1, PSA 10-15ng/ml and PSA density <0.15 had no significant difference in upgrading and adverse pathology compared to low-risk PCa. PSA>15 or GG2 were associated with a significantly greater risk of aggressive PCa. Men with low-risk CAPRA scores (0-2) and GG2 had almost a 3-fold increased risk of upgrading and 2-fold increased risk of adverse pathology compared to low-risk CAPRA GG1. CONCLUSIONS:Expanding the PSA threshold to 15 ng/ml for GG1 PCa would allow more men to choose AS and is unlikely to compromise outcomes, particularly if PSA density is low. By contrast, caution should be exercised in offering AS to men with PSA>15 or GG2.

BACKGROUND:There are no clear guidelines on how to treat posttraumatic headache (PTH) or post-concussive symptoms (PCS). However, behavioral interventions such as cognitive behavioral therapy, biofeedback, and relaxation are Level-A evidence-based treatments for headache prevention. To understand how to develop and study further mind-body interventions (MBIs) and behavioral therapies for PTH and PCS, we developed the following question using the PICO framework: Are behavioral therapies and MBIs effective for treating PTH and PCS? METHODS:We conducted a systematic search of 3 databases (Medline, PsycINFO, and EMBASE) for behavioral interventions and MBIs with the subject headings and keywords for PTH, concussion, and traumatic brain injury (TBI). Inclusion criteria were (1) randomized controlled trials, (2) the majority of the intervention had to be behavioral or mind-body therapy focused, (3) the majority of the participants (>50%) had to have had a mild TBI (not a moderate or severe TBI), (4) published in a peer-reviewed publication, and (5) meeting pre-specified primary and/or secondary outcomes. Primary outcome(s): whether there was a significant change in concussion symptom severity (yes/no) based on the symptom severity checklist/scale used, whether there was a 50% reduction in headache days and/or disability; secondary outcome(s): sleep variables, cognitive complaints, depression, and anxiety. The search identified 917 individual studies. Two independent reviewers screened citations and full-text articles independently. Nineteen articles were pulled for full article review. Seven articles met the final inclusion criteria. The systematic review was registered in Prospero (CRD42017070072). RESULTS:Overall, there was vast heterogeneity across the studies, making it difficult to fully assess efficacy. The heterogeneity ranged from differences in patient populations, the timing of when the interventions were initiated, the types of intervention implemented, and the measures used to assess outcomes. Seven studies were identified as meeting final inclusion criteria, resulting in a total of 1108 adult participants ranging from 18 to 80. Sixty-nine percent were male. Of the 7 studies, 3 were focused on military staff (retired and active). Time post-injury for inclusion into the studies varied from 48 hours post-injury to more than 2 years post-injury. One of the 7 studies did not include time post-TBI in the inclusion criteria. Two studies recruited patients who had visited their emergency departments, 4 of the studies recruited subjects through outpatient referrals, and 1 study recruited patients who had been in a prior traffic accident with resulting chronic PTH directly from a headache center. Group cognitive behavioral therapy (CBT) sessions and telephonic counseling or communication were common intervention methods used in the studies, with group CBT being used in 2 of the studies and telephonic counseling being used in 3. Other intervention methods used included individual CBT, cognitive training, psychoeducation, and computer-based and/or therapist-directed cognitive rehabilitation. CONCLUSIONS:Many of the interventions offered vastly different methods of delivery of intervention and doses of intervention. Many of the negative studies were done after an extended duration post-injury (>1-year posttraumatic brain injury [TBI]). In addition, the participants were lumped together regardless of their pre-concussion comorbidities, their mechanism of injury, their symptoms, and the duration from injury to the start of the intervention. The mass heterogeneity found between the studies led to inconclusive findings. Thus, there are various considerations for the design of the intervention for future behavioral/MBI studies for PTH and concussion that must be addressed before the leading question of this review may be effectively answered.

BACKGROUND:Hepatitis C virus (HCV) incidence has increased dramatically in the United States in recent years and is associated with the opioid epidemic due to high HCV transmission risk among people who inject drugs (PWID). HCV transmission knowledge is difficult to ascertain given the lack of psychometrically-tested measures. We developed and validated an HCV injection-risk knowledge scale. METHODS:Analyses used data from 539 New York City opioid users ages 18-29 recruited via respondent-driven sampling in 2014-16. Blood samples yielded HCV antibody status. Principal components analysis (PCA) of nine knowledge items answered true, false, or don't know identified useful scale items. We evaluated internal consistency with the Cronbach's alpha coefficient and assessed construct validity by comparing knowledge levels with those from a previously validated general HCV knowledge scale and by comparing key sub-group knowledge levels. RESULTS:PCA identified one component with five items that explained 45% of the total variance and had high internal consistency (alpha=0.91). All items referred to transmission through drug-injection equipment and practices: sharing cookers, cottons, diluting water, water containers, and cleaning syringes with water. The mean percent correct was 75%, and as expected, was moderately correlated with general HCV knowledge (Spearman's rho=0.55). As hypothesized, knowledge levels were highest for those previously tested for HCV, those with HCV antibody-positive status, PWID, and those who had received harm reduction information in various settings. CONCLUSIONS:The 5-item, validated HCV Injection-Risk Knowledge Scale (HCV-IRKS) may provide educators, care providers, and researchers with critical information for reducing HCV among PWID.

OBJECTIVE:Young black men who have sex with men (YBMSM) in the USA represent a subgroup that has the highest HIV incidence among the overall population. In the USA, pre-exposure prophylaxis (PrEP) is an effective prevention intervention to prevent HIV acquisition when taken regularly. Neighbourhood and network factors may relate to PrEP awareness, but have not been studied in YBMSM. This study aimed to examine the relationship of neighbourhood and network characteristics with PrEP awareness among YBMSM. METHODS:We used data collected from a sample of 618 YBMSM in Chicago (2013-2014). Home addresses were collected for participants and enumerated network members. Administrative data (eg, 2014 American Community Survey, Chicago Department of Public Health) were used to describe residence characteristics. Network member characteristics were also collected (eg, sexual partners' sex-drug use, confidant network members who were also MSM). Multilevel analysis was performed to examine the relationships of neighbourhood and network characteristics to PrEP awareness. RESULTS:Higher neighbourhood-level educational attainment (adjusted odds ratio (aOR) 1.02, p=0.03) and greater primary care density (aOR 1.38, p=0.01) were associated with greater PrEP awareness; greater neighbourhood alcohol outlet density (aOR 0.52, p=0.004) was associated with less PrEP awareness. Sexual network members residing in the same neighbourhood as the participants (aOR 2.58, p=0.03) and discussions around avoiding HIV acquisition with confidants (aOR 2.26, p=0.04) were associated with greater PrEP awareness. CONCLUSIONS:The results suggest that neighbourhood and network characteristics can influence PrEP awareness in YBMSM. Additional studies are needed to understand the influences of neighbourhood (eg, MSM serving venues) and network (eg, peer to peer communication) characteristics on dissemination of PrEP information, uptake and adherence and the related mechanisms behind the associations.

Alcohol outlet density has well-documented associations with social and health indicators such as crime and injury. However, significantly less is known about the relationships among alcohol-related complaints. Bayesian hierarchical Poisson regression with spatial autocorrelation was used to model the association between on- and off-premises alcohol outlet density and area-level prevalence of current drinkers and heavy drinking, and graffiti density-an indicator of physical disorder-in association with calls from civilians reporting illegal use, alcohol sales, and other alcohol-related activities (hereafter alcohol-related complaints). Complaints were separated into two groups based on whether they occurred at (a) clubs/bars/restaurants or (b) elsewhere. Alcohol-related complaints and graffiti were collected from NYC Open Data. Alcohol density data are from ESRI Business Analyst and information on the prevalence of drinking from the New York City Community Health Survey. The unit of analysis consisted of ZIP codes in New York City (n = 167), and the design was a cross-sectional analysis of aggregated data between 2009 and 2015. In multivariable models, a one-unit increase in off-premises alcohol outlet density was associated with a 47% higher risk of alcohol-related complaints at clubs, bars, and restaurants [rate ratio (RR = 1.46, 95% CI = 1.21, 1.77)]. Area-level prevalence of heavy drinking was associated with a 59% higher risk of alcohol-related complaints at the club, bars, and restaurants (RR = 1.59, 95% CI = 1.34, 1.86) and a 40% higher risk of complaints elsewhere (RR = 1.40, 95% CI = 1.20, 1.63). In New York City, area-level heavy drinking prevalence is a strong independent mechanism that links alcohol outlet density to alcohol-related complaints. Area-level heavy drinking should be investigated as a predictor of other public health problems such as drug overdose mortality.

In integrated health care systems, techniques that identify successes and opportunities for targeted improvement are needed. The authors propose a new method for estimating population health that provides a more accurate and dynamic assessment of performance and priority setting. Member data from a large integrated health system (n = 96,246, 73.8% female, mean age = 44 ± 0.01 years) were used to develop a mechanistic mathematical simulation, representing the top causes of US mortality in 2014 and their associated risk factors. An age- and sex-matched US cohort served as comparator group. The simulation was recalibrated and retested for validity employing the outcome measure of 5-year mortality. The authors sought to estimate potential population health that could be gained by improving health risk factors in the study population. Potential gains were assessed using both average life years (LY) gained and average quality-adjusted life years (QALYs) gained. The simulation validated well compared to integrated health system data, producing an AUC (area under the curve) of 0.88 for 5-year mortality. Current population health was estimated as a life expectancy of 84.7 years or 69.2 QALYs. Comparing potential health gain in the US cohort to the Kaiser Permanente cohort, eliminating physical inactivity, unhealthy diet, smoking, and uncontrolled diabetes resulted in an increase of 1.5 vs. 1.3 LY, 1.1 vs. 0.8 LY, 0.5 vs. 0.2 LY, and 0.5 vs. 0.5 LY on average per person, respectively. Using mathematical simulations may inform efforts by integrated health systems to target resources most effectively, and may facilitate goal setting.

PURPOSE OF REVIEW/OBJECTIVE:To review emerging vision-based assessments in the evaluation of concussion. RECENT FINDINGS/RESULTS:Involvement of the visual pathways is common following concussion, the mildest form of traumatic brain injury. The visual system contains widely distributed networks that are prone to neurophysiologic changes after a concussion, resulting in visual symptoms and ocular motor dysfunction. Vision-based testing is increasingly used to improve detection and assess head injury. Several rapid automatized naming (RAN) tasks, such as the King-Devick test and the Mobile Universal Lexicon Evaluation System, show capacity to identify athletes with concussion. Video-oculography (VOG) has gained widespread use in eye-tracking and gaze-tracking studies of head trauma from which objective data have shown increased saccadic latencies, saccadic dysmetria, errors in predictive target tracking, and changes in vergence in concussed individuals. SUMMARY/CONCLUSIONS:RAN tasks demonstrate promise as rapid screening tools for concussion. Further investigation will involve assessment of the role for age, characterization of learning effects over repeated measurements, and identification of optimal thresholds for clinically significant performance decrements. Various RAN tasks are likely to be functionally distinct, engaging different neural networks according to the demands of each task. Measures of saccades, smooth pursuit eye-movements, the vestibulo-ocular reflex and, more recently, disparity vergence are candidate vision-based markers for concussion. Work to adopt these assessments to the sideline or clinical environments is ongoing.

BACKGROUND:Current data suggest that opioid misuse or opioid use disorder (OUD) may be over represented among tobacco users. However, this association remains understudied in primary care settings. A better understanding of the extent of heterogeneity in opioid misuse among primary care patients who use tobacco may have implications for improved primary care-based screening, prevention, and intervention approaches. METHODS:Data were derived from a sample of 2000 adult (aged ≥18) primary care patients across 5 distinct clinics. Among past-year tobacco users (n = 882), we assessed the prevalence of opioid misuse and OUD by sociodemographic characteristics and past-year polysubstance use. Latent class analysis (LCA) was used to identify heterogeneous subgroups of tobacco users according to past-year polysubstance use patterns. Multinomial logistic regression was used to examine variables associated with LCA-defined class membership. RESULTS:Past-year tobacco use was reported by >84% of participants who reported past-year opioid misuse or OUD. Among those reporting past-year tobacco use, the prevalence of past-year opioid misuse and OUD was 14.0% and 9.5%, respectively. The prevalence of opioid misuse or OUD was highest among tobacco users who were male or unemployed. Three LCA-defined classes among tobacco users were identified including a tobacco-minimal drug use group (78.0%), a tobacco-cannabis use group (10.1%), and a tobacco-opioid/polydrug use group (11.9%). Class membership differed by sociodemographic characteristics. CONCLUSIONS:Results from this study support the benefit of more comprehensive assessment of and/or monitoring for opioid misuse among primary care patients who use tobacco, particularly for those who are male, unemployed, or polydrug users.

BACKGROUND:Criminal justice involved (CJS) populations with opioid use disorder (OUD) have high rates of relapse, future arrests, and death upon release. While medication for OUD (MOUD) reduces opioid relapse, concerns regarding diversion and stigma limit treatment in CJS populations. Extended release naltrexone (XR-NTX), as an opioid antagonist, may be more acceptable to CJS administrators. However, the impact of XR-NTX on criminal recidivism remains unknown. METHODS:Arrest data from a published randomized trial comparing XR-NTX to treatment as usual (TAU) was captured by self-report and official state arrest records. Comparisons of future arrests, time to first arrest and total number of arrests were performed using chi square tests and multivariable generalized regression models. Secondary outcomes explored differences in arrests by type and severity of crime, use of opioid and other drugs, and study phase. RESULTS:Of 308 participants randomized, 300 had arrest data. The incidence of arrests did not differ between XR-NTX (47.6%) and TAU (42.5%) participants. (ChiSq p = 0.37). Additionally, there was no significant difference in time to first arrest (adjusted HR 1.35, CI 0.96-1.89) and number of arrests per participant (adjusted IR 1.33, CI 0.78-2.27). Controlling for gender, age, previous criminal activity, and use of non-opioid drugs, logistic regression demonstrated no significant difference in incidence of arrests between groups (adjusted OR 1.38, 95% CI 0.85-2.22). CONCLUSIONS:We detected no significant difference in arrests between CJS participants with OUD randomized to XR-NTX or TAU. Despite its efficacy in reducing opioid use, XR-NTX alone may be insufficient to reduce criminal recidivism.

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer aetiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5,183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [OR_log2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [OR_SD ]= 1.08, 95%CI= 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.