Methadone dosing at New York State opioid treatment programs following initial revisions to federal regulations.

INTRODUCTION: In March 2020, a temporary federal regulatory exemption for opioid treatment programs (OTPs) was issued, allowing for a greater number of take-home methadone doses than was previously permitted. In the same month, to address financial sustainability, New York State (NYS) Medicaid also transitioned to a bundle reimbursement methodology for OTPs. We examined methadone dosing schedules in NYS before and after these regulatory and financing changes. METHODS: We conducted a retrospective cohort study using NYS OTP patient data from two sources: the client data system for a baseline period (February 2020) and survey data collected after regulatory and financing changes (May 2020 to August 2021, 64 weekly surveys). We compared methadone dosing schedules over time using chi-square tests and Poisson regression. RESULT: At baseline, data were available for 78% (n=77/99) of OTPs including 90.9% (n=26,225/28,839) of their enrolled patients. During the survey period, 99 OTPs completed 93.1% (n=5901/6336) of weekly surveys, with a mean statewide weekly patient census of 38,904 (SD=1214.5). Between February and May 2020, daily dosing significantly decreased from 55.4% to 16.3% of patients (-39.1 percentage points [95%CI: -39.8 to -38.4]), although it significantly increased subsequently (3.33%/4-weeks [95%CI: 3.28, 3.39]). In addition, weekly-to-monthly dosing significantly increased from 26.9% to 54.5% of patients (27.6 percentage points [95%CI: 26.9, 28.4]), although it significantly decreased subsequently (-1.19%/4-weeks [95%CI: -1.23, -1.15]). DISCUSSION: Despite large initial changes, we found a trend toward gradual return to more restrictive dosing schedules. OTPs need further support in leveraging new opportunities to improve methadone treatment and outcomes.

Public health detailing to increase naloxone access in NYC pharmacies.

BACKGROUND: Drug overdose is a public health crisis in the United States. Opioid overdose deaths are preventable using naloxone, an opioid antagonist that reverses the effect of an opioid and prevents fatal overdose. OBJECTIVES: This study aimed to evaluate changes in naloxone standing order status, attitudes, and practice behavior after an 8-week public health detailing campaign on increasing naloxone access conducted among pharmacists in independent pharmacies in New York City (NYC). METHODS: Campaign recommendations were to (1) enroll in the NYC pharmacy naloxone standing order program, (2) offer naloxone to at-risk patients, and (3) educate patients on how to use naloxone. Evaluation was performed using initial and follow-up surveys administered to pharmacists during detailing visits and Department of Health and Mental Hygiene data on pharmacies in the standing order program. RESULTS: Detailing visits were completed with 1153 pharmacists; follow-up visits were completed with 457 (40%). Self-reported attitudes and practice behavior related to the 3 campaign recommendations improved (P < 0.01). After the campaign, 519 new pharmacies enrolled in the standing order program. CONCLUSIONS: The detailing campaign substantially increased the number of pharmacies enrolled in the standing order program and was associated with improved attitudes and practice behavior related to naloxone provision to varying degrees. Other jurisdictions could consider detailing pharmacists as a strategy to increase naloxone access.

Multimorbidity and Inpatient Utilization Among Older Adults with Opioid Use Disorder in New York City.

BACKGROUND: Nationally, there is a sharp increase in older adults with opioid use disorder (OUD). However, we know little of the acute healthcare utilization patterns and medical comorbidities among this population. OBJECTIVE: This study describes the prevalence of chronic conditions, patterns of inpatient utilization, and correlates of high inpatient utilization among older adults with OUD in New York City (NYC). DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Patients aged ≥55 with OUD hospitalized in NYC in 2012 identified using data from New York State's Statewide Planning and Research Cooperative System (SPARCS). MAIN MEASURES: The prevalence of comorbid substance use diagnoses, chronic medical disease, and mental illness was measured using admission diagnoses from the index hospitalization. We calculated the ICD-Coded Multimorbidity-Weighted Index (MWI-ICD) for each patient to measure multimorbidity. We followed the cohort through September 30, 2015 and the outcome was the number of rehospitalizations for inpatient services in NYC. We compared patient-level factors between patients with the highest use of inpatient services (≥7 rehospitalizations) during the study period to low utilizers. We used multiple logistic regression to examine possible correlates of high inpatient utilization. KEY RESULTS: Of 3669 adults aged ≥55 with OUD with a hospitalization in 2012, 76.4% (n=2803) had a subsequent hospitalization and accounted for a total of 22,801 rehospitalizations during the study period. A total of 24.7% of the cohort (n=906) were considered high utilizers and had a higher prevalence of alcohol and cocaine-related diagnoses, congestive heart failure, diabetes, schizophrenia, and chronic obstructive pulmonary disease. Multivariable predictors of high utilization included being a Medicaid beneficiary (adjusted odds ratio [aOR]=1.70, 95% confidence interval [CI]=1.37-2.11), alcohol-related diagnoses (aOR=1.43, 95% CI: 1.21-1.69), and increasing comorbidity measured by MWI-ICD (highest MWI-ICD quartile: aOR=1.98, 95% CI=1.59-2.48). CONCLUSIONS: Among older adults with OUD admitted to the hospital, multimorbidity is strongly associated with high inpatient utilization.

Increasing Access to Buprenorphine in Safety-Net Primary Care Clinics: The New York City Buprenorphine Nurse Care Manager Initiative.

The Buprenorphine Nurse Care Manager Initiative (BNCMI) sought to increase access to opioid use disorder treatment in underserved New York City populations by expanding buprenorphine treatment capacity in safety-net primary care clinics.During 2016 to 2020, BNCMI added 116 new buprenorphine providers across 27 BNCMI clinics, and 1212 patients were enrolled; most patients identified as Latinx or Hispanic and were Medicaid beneficiaries.BNCMI increased access to buprenorphine, reached underserved populations, and is part of the New York City Health Department's multipronged approach to reducing opioid overdose deaths.

Using Urine Drug Testing to Estimate the Prevalence of Drug Use : Lessons Learned From the New York City Health and Nutrition Examination Survey, 2013-2014.

OBJECTIVES: Estimating the prevalence of drug use in the general population is important given its potential health consequences but is challenging. Self-reported surveys on drug use have inherent limitations that underestimate drug use. We evaluated the performance of linking urine drug testing with a local, representative health examination survey in estimating the prevalence of drug use in New York City (NYC). METHODS: We used urine drug testing from the NYC Health and Nutrition Examination Survey (NYC HANES) to estimate the prevalence of drug use (benzodiazepines, cocaine, heroin, and opioid analgesics) among the study sample and compare the findings with self-reported responses to questions about past-12-month drug use from the same survey. RESULTS: Of 1527 respondents to NYC HANES, urine drug testing was performed on 1297 (84.9%) participants who provided urine and consented to future studies. Self-reported responses gave past-12-month weighted estimates for heroin, cocaine, or any prescription drug misuse of 13.8% (95% CI, 11.6%-16.3%), for prescription drug misuse of 9.9% (95% CI, 8.1%-12.1%), and for heroin or cocaine use of 6.1% (95% CI, 4.7%-7.9%). Urine drug testing gave past-12-month weighted estimates for any drug use of 4.3% (95% CI, 3.0%-6.0%), for use of any prescription drug of 2.8% (95% CI, 1.9%-4.1%), and for heroin or cocaine use of 2.0% (95% CI, 1.2%-3.6%). CONCLUSION: Urine drug testing provided underestimates for the prevalence of drug use at a population level compared with self-report. Researchers should use other methods to estimate the prevalence of drug use on a population level.

Trends in inpatient discharges with drug or alcohol admission diagnoses to a skilled nursing facility among older adults, New York City 2008-2014.

BACKGROUND: Recent research shows an increase in drug and alcohol-related hospitalizations in the USA, especially among older adults. However, no study examines trends in discharges to a skilled nursing facility (SNF) after a drug or alcohol-related hospitalization. Older adults are more likely to need post-hospital care in a SNF after a hospitalization due to an increased presence of chronic diseases and functional limitations. Therefore, the objective of this study was to estimate trends in drug or alcohol-related hospitalizations with discharge to a SNF among adults age 55 and older. METHODS: We analyzed data from New York State's Statewide Planning and Research Cooperative System to calculate the number of cannabis, cocaine, opioid, and alcohol-related hospitalizations in New York City that resulted in discharge to a SNF from 2008 to 2014 among adults age 55 and older. Using New York City population estimates modified from US Census Bureau, we calculated age-specific rates per 100,000 adults. Trend tests were estimated using joinpoint regressions to calculate annual percentage change (APC) with 95% confidence intervals (CI) and stratified by adults age 55-64 and adults age 65 and older. RESULTS: During the study period, among adults age 55-64, there were significant increases in cocaine, cannabis, and opioid-related hospitalizations that resulted in discharge to a SNF. For adults ≥ 65 years, there were sharp increases across all substances with larger increases in opioids (APC of 10.66%) compared to adults 55-64 (APC of 6.49%). For both age groups and among the four substances, alcohol-related hospitalizations were the leading cause of discharge to a SNF. CONCLUSIONS: We found an increase in hospital discharges to SNFs for patients age 55 and older admitted with alcohol or drug-related diagnoses. Post-acute and long-term care settings should prepare to care for an increase in older patients with substance use disorders by integrating a range of harm reduction interventions into their care settings.

Examining opioid-involved overdose mortality trends prior to fentanyl: New York City, 2000-2015.

BACKGROUND: Rates of overdose death in New York City (NYC) increased 26% from 2000 to 2015, with a notable decrease in rate from 2006 to 2010. Beginning in 2016, the synthetic opioid fentanyl entered the NYC illicit drug market and has been associated with large increases in overdose death. This study assessed NYC trends in opioid-involved overdose death prior to fentanyl to understand the contribution of specific opioids and inform overdose prevention strategies. METHODS: Data were derived from death certificates linked to postmortem toxicology testing. We stratified cases into three mutually exclusive groups: (1) heroin without opioid analgesics (OAs); (2) OAs without heroin; and (3) the combination of heroin and OAs. We calculated mortality rates by year, and compared rates by the demographic characteristics age, sex, and race/ethnicity. Joinpoint regression identified junctures in trends between 2000 and 2015. RESULTS: Rates of overdose death involving heroin without OAs decreased from 2006 to 2010, then increased from 2010 to 2015 among males, persons age 15 to 54, and Blacks and Whites. Rates of overdose death involving OAs with and without heroin increased from 2000 to 2015 across all demographic subgroups. CONCLUSIONS: The identified trends in overdose death are suggestive of demographic shifts in drug use. In particular, the tamper-resistant reformulation of oxycodone 80 mg may have increased the use of heroin among primary OA users. Notably, older adults may have had established heroin use practices prior to the proliferation of OAs and thus may have been less likely to modify drug use practices.

Alcohol-related emergency department visits and income inequality in New York City, USA: an ecological study.

OBJECTIVES: Previous research has found that greater income inequality is related to problematic alcohol use across a variety of geographical areas in the USA and New York City (NYC). Those studies used self-reported data to assess alcohol use. This study examined the relationship between within-neighborhood income inequality and alcohol-related emergency department (ED) visits. METHODS: The study outcome was the alcohol-related ED visit rate per 10,000 persons between 2010 and 2014, using data obtained from the New York Statewide Planning and Research Cooperative System. The main predictor of interest was income inequality, measured using the Gini coefficient from the American Community Survey (2010-2014) at the public use microdata area (PUMA) level (n=55) in NYC. Variables associated with alcohol-related ED visits in bivariate analyses were considered for inclusion in a multivariable model. RESULTS: There were 420,568 alcohol-related ED visits associated with a valid NYC address between 2010 and 2014. The overall annualized NYC alcohol-related ED visit rate was 100.7 visits per 10,000 persons. The median alcohol ED visit rate for NYC PUMAs was 88.0 visits per 10,000 persons (interquartile range [IQR], 64.5 to 133.5), and the median Gini coefficient was 0.48 (IQR, 0.45 to 0.51). In the multivariable model, a higher neighborhood Gini coefficient, a lower median age, and a lower percentage of male residents were independently associated with the alcohol-related ED visit rate. CONCLUSIONS: This study found that higher neighborhood income inequality was associated with higher neighborhood alcohol-related ED visit rates. The precise mechanism of this relationship is not understood, and further investigation is warranted to determine temporality and to assess whether the results are generalizable to other locales.

Estimated impact of supervised injection facilities on overdose fatalities and healthcare costs in New York City.

BACKGROUND: The opioid epidemic in the United States has resulted in over 42,000 U.S. opioid overdose fatalities in 2016 alone. In New York City (NYC) opioid overdoses have reached a record high, increasing from 13.6 overdose deaths/100,000 to 19.9/100,000 from 2015 to 2016. Supervised injection facilities (SIFs) provide a hygienic, safe environment in which pre-obtained drugs can be consumed under clinical supervision to quickly reverse opioid overdoses. While SIFs have been implemented worldwide, none have been implemented to date in the United States. This study estimates the potential impact on opioid overdose fatalities and healthcare system costs of implementing SIFs in NYC. METHODS: A deterministic model was used to project the number of fatal opioid overdoses avoided by implementing SIFs in NYC. Model inputs were from 2015 to 2016 NYC provisional overdose data (N = 1852) and the literature. Healthcare utilization and costs were estimated for fatal overdoses that would have been avoided from implementing one or more SIFs. RESULTS: One optimally placed SIF is estimated to prevent 19-37 opioid overdose fatalities annually, representing a 6-12% decrease in opioid overdose mortality for that neighborhood; four optimally placed SIFs are estimated to prevent 68-131 opioid overdose fatalities. Opioid overdoses cost the NYC healthcare system an estimated $41 million per year for emergency medical services, emergency department visits, and hospitalizations. Implementing one SIF is estimated to save $0.8-$1.6 million, and four SIFs saves $2.9-$5.7 million in annual healthcare costs from opioid overdoses. CONCLUSIONS: Implementing SIFs in NYC would save lives and healthcare system costs, although their overall impact may be limited depending on the geographic characteristic of the local opioid epidemic. In cities with geographically dispersed opioid epidemics such as NYC, multiple SIFs will be required to have a sizeable impact on the total number of opioid overdose fatalities occurring each year.

Impact of a prescription drug monitoring program use mandate on potentially problematic patterns of opioid analgesic prescriptions in New York City.

PURPOSE: To evaluate New York State's mandate that prescribers query the prescription drug monitoring program (PDMP) prior to prescribing Schedule II-IV medications. METHODS: We conducted an interrupted time series analysis of opioid analgesic prescriptions dispensed to adult New York City (NYC) residents using data from New York State's PDMP. Our main outcomes were the rate of (a) greater than or equal to five prescriber episodes, (b) greater than or equal to five prescriber and greater than or equal to five pharmacy episodes, and (c) paying for prescriptions with both cash and insurance, per quarter, per 100 000 NYC residents. We defined three periods: (a) the baseline period (January 2011 to July 2012), (b) the anticipatory period (September 2012 to July 2013) after mandate law enactment but before mandate implementation, and (c) the postmandate period (September 2013 to December 2015). For each outcome, we used autoregressive linear regression models to account for correlation in outcomes over time. RESULTS: At the end of the postmandate period, the rate of greater than or equal to five prescriber episodes was 58% lower than expected (absolute difference: -17.2 per 100 000 NYC residents; 95% CI, -31.2 to -3.1), the rate of greater than or equal to five prescriber and greater than or equal to five pharmacy episodes was 88% lower than expected (absolute difference: -8.6; 95% CI, -11.0 to -6.3), and the rate of cash and insurance payment episodes was 50% lower than expected (absolute difference: -145.4; 95% CI, -279.4 to -11.6). CONCLUSIONS: While outcomes were relatively rare, New York State's PDMP mandate was associated with significant decreases in rates of potentially problematic patterns of opioid analgesic prescriptions.

Unintentional drug overdose deaths involving cocaine among middle-aged and older adults in New York City.

BACKGROUND: Cocaine is commonly involved in unintentional drug poisoning (overdose) deaths, accounting for 46% of overdose deaths in New York City (NYC) in 2016. However, little research exists regarding cocaine use by middle-aged and older adults, who are more likely than younger individuals to have underlying cardiovascular disease (CVD) and therefore, may be at increased risk for the adverse health consequences of cocaine. METHODS: We conducted a retrospective analysis of unintentional drug overdose deaths of middle-aged and older NYC residents age 45-84 from 2000 to 2016 using two linked sources, NYC death certificates and toxicology results from the Office of the Chief Medical Examiner. RESULTS: From 2000 to 2016, there were 6061 unintentional drug overdose deaths among New Yorkers age 45-84. Of those, cocaine was involved in 53% (n = 3183). Co-occurring opioid involvement (fentanyl, heroin, methadone, or opioid analgesics) among deaths involving cocaine was common (58%). Compared to decedents of non-cocaine involved overdose, decedents of cocaine-involved overdose were more likely to be male and non-Latino Black. Multivariable analysis showed that adults age 45-54 (adjusted odds ratio [AOR] = 1.34, 95% 1.05, 1.70), males (AOR = 1.30, 95% CI 1.15, 1.46), Bronx residence (AOR = 1.29, 95% CI 1.08, 1.54), and non-Latino black race/ethnicity (AOR = 2.37, 95% CI 2.07, 2.72) were independently associated with cocaine-involved overdose. CONCLUSION: Characteristics of decedents of cocaine-involved overdose overlap with populations with high CVD burden in NYC. Studies are needed to better understand the risks of cocaine among adults with underlying CVD.

Witnessed overdoses and naloxone use among visitors to Rikers Island jails trained in overdose rescue.

With the opioid overdose mortality rates rising nationally, The New York City Department of Health and Mental Hygiene (NYC DOHMH) has worked to expand overdose rescue training (ORT) and naloxone distribution. This study sought to determine rates of overdose witnessing and naloxone use among overdose rescue-trained visitors to the NYC jails on Rikers Island. We conducted a six-month prospective study of visitors to NYC jails on Rikers Island who received ORT. We collected baseline characteristics of study participants, characteristics of overdose events, and responses to witnessed overdose events, including whether the victim was the incarcerated individual the participant was visiting on the day of training. Bivariate analyses compared baseline characteristics of participants who witnessed overdoses to those who did not, and of participants who used naloxone to those who did not. Overall, we enrolled 283 participants visiting NYC's Rikers Island jails into the study. Six months after enrollment, we reached 226 participants for follow-up by phone. 40 participants witnessed 70 overdose events, and 28 participants reported using naloxone. Of the 70 overdose events, three victims were the incarcerated individuals visited on the day of training; nine additional victims were recently released from jail and/or prison. Visitors to persons incarcerated at Rikers Island witness overdose events and are able to perform overdose rescues with naloxone. This intervention reaches a population that includes not only those recently released, but also other people who experienced overdose.

Public Health Detailing-A Successful Strategy to Promote Judicious Opioid Analgesic Prescribing.

OBJECTIVES: To evaluate knowledge and prescribing changes following a 2-month public health detailing campaign (one-to-one educational visits) about judicious opioid analgesic prescribing conducted among health care providers in Staten Island, New York City, in 2013. METHODS: Three detailing campaign recommendations were (1) a 3-day supply of opioids is usually sufficient for acute pain, (2) avoid prescribing opioids for chronic noncancer pain, and (3) avoid high-dose opioid prescriptions. Evaluation consisted of a knowledge survey, and assessing prescribing rates and median day supply per prescription. Prescribing data from the 3-month period before the campaign were compared with 2 sequential 3-month periods after the campaign. RESULTS: Among 866 health care providers visited, knowledge increased for all 3 recommendations (P < .01). After the campaign, the overall prescribing rate decreased similarly in Staten Island and other New York City counties (boroughs), but the high-dose prescribing rate decreased more in Staten Island than in other boroughs (P < .01). Median day supply remained stable in Staten Island and increased in other boroughs. CONCLUSIONS: The public health detailing campaign improved knowledge and likely prescribing practices and could be considered by other jurisdictions to promote judicious opioid prescribing.

Buprenorphine infrequently found in fatal overdose in New York City.

BACKGROUND: Buprenorphine is an opioid agonist medication that is both safe and effective in the treatment of opioid use disorders and the prevention of opioid overdoses. Despite this, media coverage has highlighted public concerns about the potential safety consequences of buprenorphine misuse and diversion. To address the possible contribution of buprenorphine to overdose mortality, we systematically tested post mortem blood specimens from decedents who had died of an unintentional drug overdoses in 2013. METHODS: We retrospectively tested consecutive drug overdose cases that occurred from June through October 2013. Cases with available blood specimens were tested for buprenorphine and norbuprenorphine using liquid chromatography-tandem mass spectrometry. Toxicology results were linked to death certificates and case files from New York City Vital Statistics and New York City Office of the Chief Medical Examiner. RESULTS: Of the 98 unintentional drug overdose fatalities tested, only 2 (2.0%) tested positive for buprenorphine metabolites. All 98 unintentional fatalities involved multiple substances. CONCLUSIONS: Buprenorphine was infrequently found in drug overdose deaths in New York City. Since the safety and efficacy of buprenorphine are well documented, and overdoses resulting from buprenorphine treatment or diversion are very rare, facilitating access to buprenorphine treatment is strongly recommended.

Decrease in rate of opioid analgesic overdose deaths - Staten Island, New York City, 2011-2013.

From 2000 to 2011, the rate of unintentional drug poisoning (overdose) deaths involving opioid analgesics increased 435% in Staten Island, from 2.0 to 10.7 per 100,000 residents. During 2005-2011, disparities widened between Staten Island and the other four New York City (NYC) boroughs (Bronx, Brooklyn, Manhattan, and Queens); in 2011, the rate in Staten Island was 3.0-4.5 times higher than in the other boroughs. In response, the NYC Department of Health and Mental Hygiene (DOHMH) implemented a comprehensive five-part public health strategy, with both citywide and Staten Island-targeted efforts: 1) citywide opioid prescribing guidelines, 2) a data brief for local media highlighting Staten Island mortality and prescribing data, 3) Staten Island town hall meetings convened by the NYC commissioner of health and meetings with Staten Island stakeholders, 4) a Staten Island campaign to promote prescribing guidelines, and 5) citywide airing of public service announcements with additional airing in Staten Island. Concurrently, the New York state legislature enacted the Internet System for Tracking Over-Prescribing (I-STOP), a law requiring prescribers to review the state prescription monitoring system before prescribing controlled substances. This report describes a 29% decline in the opioid analgesic-involved overdose death rate in Staten Island from 2011 to 2013, while the rate did not change in the other four NYC boroughs, and compares opioid analgesic prescribing data for Staten Island with data for the other boroughs. Targeted public health interventions might be effective in lowering opioid analgesic-involved overdose mortality rates.

Unintentional opioid overdose deaths in New York City, 2005-2010: a place-based approach to reduce risk.

BACKGROUND: Drug poisoning is the leading cause of death from injuries in the United States. In New York City (NYC), unintentional drug poisoning death is the third leading cause of premature death, and opioids are the most commonly occurring class of drugs. Opioid overdose prevention efforts aim to decrease the number of people at risk for overdose and to decrease fatality rates among those using opioids by improving overdose response. These strategies can be enhanced with a comprehensive understanding of the settings in which overdoses occur. METHODS: A cross-sectional analysis of unintentional opioid poisoning deaths in NYC from 2005 to 2010 (n=2649). Bivariate and multivariate analyses were performed to identify factors associated with settings of fatal opioid overdose. RESULTS: Three-quarters of the sample overdosed in a home; one-tenth in an institution, and the remaining in a public indoor setting, the outdoors or another non-home setting. Factors associated with overdosing at home include female gender, college degree, residence in the borough of Staten Island, and combined use of opioid analgesics and benzodiazepines. Factors associated with overdosing outside of the home include ages 35-64, residence in Manhattan, and use of heroin. CONCLUSION: The sample represents a near census of unintentional opioid overdose deaths in NYC during the study period, and allows for the identification of demographic and drug-using patterns by setting of overdose. Because most opioid overdoses occur inside the home, opioid overdose response programs can most efficiently address the epidemic by both reducing the risk of overdose in the home and targeting those who may be in the home at the time of an overdose for overdose response training. Approaches include minimizing risk of misuse and diversion through safe storage and safe disposal programs, physician education on prescribing of opioid analgesics and benzodiazepines, prescription of take-home naloxone, and Good Samaritan laws.

Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk.

BACKGROUND: Testicular germ cell tumor (TGCT) incidence increased steadily in recent decades, but causes remain elusive. Germ cell function may be influenced by cannabinoids, and 2 prior epidemiologic studies reported that the use of marijuana may be associated with nonseminomatous TGCT. Here, the authors evaluate the relation between TGCTs and exposure to marijuana and other recreational drugs using a population-based case-control study. METHODS: In total, 163 patients who were diagnosed with TGCT in Los Angeles County from December 1986 to April 1991 were enrolled, and 292 controls were matched on age, race/ethnicity, and neighborhood. Participants were asked about drug use by a structured, in-person interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression analysis adjusted for history of cryptorchidism; education; religiosity; and reported use of marijuana, cocaine, and amyl nitrite. RESULTS: Compared with never use, ever use of marijuana had a 2-fold increased risk (OR, 1.94; 95% CI, 1.02-3.68), whereas ever use of cocaine had a negative association with TGCT (OR, 0.54; 95% CI, 0.32-0.91). Stratification on tumor histology revealed a specific association of marijuana use with nonseminoma and mixed histology tumors (OR, 2.42; 95% CI, 1.08-5.42). CONCLUSIONS: A specific association was observed between marijuana use and the risk of nonseminoma and mixed tumors. To the authors' knowledge, this is the first report of a negative association between cocaine use and TGCT risk. The current results warrant mechanistic studies of marijuana's effect on the endocannabinoid system and TGCT risk and caution that recreational and therapeutic use of cannabinoids by young men may confer malignant potential to testicular germ cells.

Cryptorchidism and testicular germ cell tumors: comprehensive meta-analysis reveals that association between these conditions diminished over time and is modified by clinical characteristics.

INTRODUCTION: Risk of testicular germ cell tumors (TGCT) is consistently associated with a history of cryptorchidism (CO) in epidemiologic studies. Factors modifying the association may provide insights regarding etiology of TGCT and suggest a basis for individualized care of CO. To identify modifiers of the CO-TGCT association, we conducted a comprehensive, quantitative evaluation of epidemiologic data. MATERIALS AND METHODS: Human studies cited in PubMed or ISI Web of Science indices through December 2011 and selected unpublished epidemiologic data were reviewed to identify 35 articles and one unpublished dataset with high-quality data on the CO-TGCT association. Association data were extracted as point and 95% confidence interval estimates of odds ratio (OR) or standardized incidence ratio (SIR), or as tabulated data. Values were recorded for each study population, and for subgroups defined by features of study design, CO and TGCT. Extracted data were used to estimate summary risk ratios (sRR) and evaluate heterogeneity of the CO-TGCT association between subgroups. RESULTS: The overall meta-analysis showed that history of CO is associated with four-fold increased TGCT risk [RR = 4.1(95% CI = 3.6-4.7)]. Subgroup analyses identified five determinants of stronger association: bilateral CO, unilateral CO ipsilateral to TGCT, delayed CO treatment, TGCT diagnosed before 1970, and seminoma histology. CONCLUSIONS: Modifying factors may provide insight into TGCT etiology and suggest improved approaches to managing CO. Based on available data, CO patients and their parents or caregivers should be made aware of elevated TGCT risk following orchidopexy, regardless of age at repair, unilateral vs. bilateral non-descent, or position of undescended testes.

Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis.

CONTEXT: Many studies have investigated the association between male infertility and trinucleotide repeat polymorphisms in the androgen receptor (AR) gene, but no comprehensive meta-analysis of all published studies has been conducted. OBJECTIVE: Our goals were to summarize published data on associations between AR CAG and GGC repeat lengths and male infertility and investigate sources of variation between study results. DATA SOURCES: We searched for reports published before October 2006 using Medline, PubMed, and Web of Science. STUDY SELECTION: All selected studies included the following: a case group with infertility as measured by semen parameters, a control group of known or presumed fertile men, and measurement of CAG and/or GGC repeat lengths among cases and controls. Thirty-nine reports were selected based on these criteria, and 33 were ultimately included in the meta-analysis. DATA EXTRACTION: One investigator extracted data on sample size, mean and sd of trinucleotide repeat length, and study characteristics. DATA SYNTHESIS: Estimates of the standardized mean difference (95% confidence interval) were 0.19 (0.09-0.29) for the 33 studies and 0.31 (0.14-0.47) for a subset of 13 studies that used more stringent case and control selection criteria. Thus, in both groups, cases had statistically significantly longer CAG repeat length than controls. Publication date appeared to be a significant source of variation between studies. CONCLUSIONS: This meta-analysis provides support for an association between increased androgen receptor CAG length and idiopathic male infertility, suggesting that even subtle disruptions in the androgen axis may compromise male fertility.