Physician Prescribing of Opioids to Patients at Increased Risk of Overdose From Benzodiazepine Use in the United States.

Importance: Recent increases in US opioid-related deaths underscore the need to understand drivers of fatal overdose. The initial prescription of opioids represents a critical juncture because it increases the risk of future opioid use disorder and is preventable. Objective: To examine new opioid prescribing patterns in US patients at increased risk of overdose from benzodiazepine use. Design, Setting, and Participants: This study used publicly available data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from January 1, 2005, through December 31, 2015, to identify adults 20 years or older receiving new opioid prescriptions and concurrently using a benzodiazepine. Main Outcomes and Measures: Population-based rates of new opioid prescriptions stratified by use of benzodiazepines. Results: This study analyzed 13 146 visits, representing 214 million visits nationally, with a new opioid prescription. Rates of new opioid prescriptions among adults using a benzodiazepine increased from 189 to 351 per 1000 persons between 2005 and 2010 (rate difference, 162; 95% CI, 29-295; P = .02) and decreased to 172 per 1000 persons by 2015 (rate difference, -179; 95% CI, -310 to -48; P = .008). New opioid prescriptions in the general population not using benzodiazepines increased nonsignificantly from 78 to 93 per 1000 US persons between 2005 and 2010 (rate difference, 15; 95% CI, -3 to 33; P = .10) and decreased nonsignificantly to 79 per 1000 persons by 2015 (rate difference, -14; 95% CI, -38 to 11; P = .28). The likelihood of receiving a new opioid prescription during an ambulatory visit remained higher for patients concurrently using benzodiazepines compared with the general population after adjusting for demographic characteristics, comorbidities, and diagnoses associated with pain (adjusted relative risk, 1.83; 95% CI, 1.56-2.15; P < .001). Naloxone was coprescribed in less than 1% of visits when a patient concurrently used a benzodiazepine. Conclusions and Relevance: In 2010, new opioid prescriptions for US adults stopped increasing and began to decrease among higher-risk patients who used benzodiazepines. These patterns suggest that the recent increase in opioid-related deaths may be associated with factors other than physicians writing new opioid prescriptions. Nevertheless, prescribing among higher-risk patients still occurred at rates higher than rates in the general population, representing an important opportunity to improve quality of care for patients experiencing pain.

Feasibility Study on Applying Radiophotoluminescent Glass Dosimeters for CyberKnife SRS Dose Verification.

CyberKnife is one of multiple modalities for stereotactic radiosurgery (SRS). Due to the nature of CyberKnife and the characteristics of SRS, dose evaluation of the CyberKnife procedure is critical. A radiophotoluminescent glass dosimeter was used to verify the dose accuracy for the CyberKnife procedure and validate a viable dose verification system for CyberKnife treatment. A radiophotoluminescent glass dosimeter, thermoluminescent dosimeter, and Kodak EDR2 film were used to measure the lateral dose profile and percent depth dose of CyberKnife. A Monte Carlo simulation for dose verification was performed using BEAMnrc to verify the measured results. This study also used a radiophotoluminescent glass dosimeter coupled with an anthropomorphic phantom to evaluate the accuracy of the dose given by CyberKnife. Measurements from the radiophotoluminescent glass dosimeter were compared with the results of a thermoluminescent dosimeter and EDR2 film, and the differences found were less than 5%. The radiophotoluminescent glass dosimeter has some advantages in terms of dose measurements over CyberKnife, such as repeatability, stability, and small effective size. These advantages make radiophotoluminescent glass dosimeters a potential candidate dosimeter for the CyberKnife procedure. This study concludes that radiophotoluminescent glass dosimeters are a promising and reliable dosimeter for CyberKnife dose verification with clinically acceptable accuracy within 5%.

Is Obesity Associated With School Dropout? Key Developmental and Ethnic Differences.

BACKGROUND: We aimed to expand the literature on child obesity and school outcomes by examining associations between obesity and high school dropout, including the role of obesity onset and duration as well as ethnicity. METHODS: Data on 5066 children obtained between 1986 and 2010 from the child cohort of the 1979 National Longitudinal Study of Youth (NLSY79) were analyzed. Group-based trajectory analysis identified obesity trajectories from 6 to 18 years. School completion information from age 14 into young adulthood was used to calculate school dropout. Chi-square and pairwise comparison tests were used to identify significant associations between obesity trajectories and school dropout. RESULTS: Adolescents belonging to an increasing trajectory (adolescent-onset obesity) had a higher likelihood of dropping out of high school compared with those belonging to chronic, decreasing (childhood-only obesity), and nonobese trajectories. This association was particularly salient among white adolescents. CONCLUSIONS: Obesity onset during early adolescence increased risk of high school dropout. White adolescents were particularly vulnerable. Given that early adolescence is marked by significant biological and social changes, future research should seek to identify the underlying processes linking adolescent obesity and school dropout to decrease school dropout risk among this vulnerable population.

Trajectory of Adolescent Obesity: Exploring the Impact of Prenatal to Childhood Experiences.

This study examined longitudinal associations of prenatal exposures as well as childhood familial experiences with obesity status from ages 10 to 18. Hierarchical generalized linear modeling (HGLM) was applied to examine 5,156 adolescents from the child sample of the 1979 National Longitudinal Survey of Youth (NLSY79). Higher maternal weight, maternal smoking during pregnancy, lower maternal education, and lack of infant breastfeeding were contributors to elevated adolescent obesity risk in early adolescence. However, maternal age, high birth weight of child, and maternal annual income exhibited long-lasting impact on obesity risk over time throughout adolescence. Additionally, childhood familial experiences were significantly related to risk of adolescent obesity. Appropriate use of family rules in the home and parental engagement in children's daily activities lowered adolescent obesity risk, but excessive television viewing heightened adolescent obesity risk. Implementation of consistent family rules and parental engagement may benefit adolescents at risk for obesity.

Association between adolescent substance use and obesity in young adulthood: a group-based dual trajectory analysis.

PURPOSE: This study investigated whether and how trajectories of substance use in adolescence were associated with obesity trajectories in young adulthood. We hypothesized that: (1) exposure to persistent substance use throughout adolescence may heighten obesity risk in young adulthood; and (2) such associations may differ once gender, ethnicity, socioeconomic status, and obesity status in adolescence, are considered. METHODS: The study included 5141 adolescents from the child sample of the 1979 National Longitudinal Survey of Youth and utilized biennial data across the 12 assessments (1986-2008) to examine trajectories of substance use behaviors (i.e., cigarette smoking, alcohol use, and marijuana use) from ages 12 to 18 and obesity trajectories from ages 20 to 24. Group-based dual trajectory modeling was applied to examine sequential associations of trajectories of each type of substance use behavior with obesity trajectories. RESULTS: Three distinctive trajectory patterns were respectively identified for cigarette smoking, alcohol use, and marijuana use from ages 12 to 18, as well as for obesity status (BMI ≥ 30) from ages 20 to 24. Taking into account gender, ethnicity, socioeconomic status, and obesity status in adolescence, adolescents with the most problematic smoking trajectory (High-decreasing) were more likely to exhibit a High-obesity trajectory from ages 20 to 24. Also, adolescents with an Increasing marijuana use trajectory were more likely to exhibit an Increased obesity trajectory in young adulthood. CONCLUSIONS: The current study demonstrates that adolescent substance use is associated with subsequent obesity in young adulthood. The associations appear to differ based on the type of substance use and patterns of use.

A Latent Class Analysis of Maternal Responsiveness and Autonomy-Granting in Early Adolescence: Prediction to Later Adolescent Sexual Risk-Taking.

The present study sought to extend empirical inquiry related to the role of parenting on adolescent sexual risk-taking by using latent class analysis (LCA) to identify patterns of adolescent-reported mother responsiveness and autonomy-granting in early adolescence and examine associations with sexual risk-taking in mid- and late-adolescence. Utilizing a sample of 12- to 14-year-old adolescents (N = 4,743) from the 1997 National Longitudinal Survey of Youth (NLSY97), results identified a four-class model of maternal responsiveness and autonomy-granting: low responsiveness/high autonomy-granting, moderate responsiveness/moderate autonomy-granting, high responsiveness/low autonomy-granting, high responsiveness/moderate autonomy-granting. Membership in the low responsiveness/high autonomy-granting class predicted greater sexual risk-taking in mid- and late-adolescence compared to all other classes, and membership in the high responsiveness/ moderate autonomy-granting class predicted lower sexual risk-taking. Gender and ethnic differences in responsiveness and autonomy-granting class membership were also found, potentially informing gender and ethnic disparities of adolescent sexual risk-taking.

Concurrent life-course trajectories of employment and marijuana-use: exploring interdependence of longitudinal outcomes.

This study analyzes data on 7661 individuals who participated in the 1979 National Longitudinal Survey of Youth (NLSY79) to estimate trajectories of employment and marijuana-use over a 17-year period. Bivariate random intercept and slope modeling is applied to examine concurrently the cross-correlation between the two concurrent longitudinal trajectories from age 23 to 39. Parameter estimates indicate baseline level (at age 23) of employment to be negatively correlated with marijuana, suggesting marijuana-use is associated with lower workforce productivity at age 23. The longitudinal employment slope is positively correlated with employment intercept for both males and females, indicating that survey participants with higher levels of employment at age 23 are more likely to have a positive impact on employment trajectory over time. For males, however, the employment slope is also significantly correlated with marijuana intercept (r=-0.07), indicating marijuana-use in early adulthood may uniquely lower workforce productivity over age.

Developmental trajectories of childhood obesity and risk behaviors in adolescence.

Using group-based trajectory modeling, this study examined 5156 adolescents from the child sample of the 1979 National Longitudinal Survey of Youth to identify developmental trajectories of obesity from ages 6-18 and evaluate associations of such trajectories with risk behaviors and psychosocial health in adolescence. Four distinctive obesity trajectories were identified: "Chronically Obese," "Decreasing," "Increasing," and "Non-obese." Males were overrepresented in the Chronically Obese and Increasing groups; females were overrepresented in the Decreasing group. African-Americans were overrepresented in the Chronically Obese, Increasing, and Decreasing groups; in contrast, Whites were overrepresented in the Non-obese group. Obesity trajectories were not associated with greater trends in alcohol use, marijuana use, or delinquency, but Chronically Obese adolescents showed a greater increase in cigarette smoking over time compared to other trajectories. The Increasing trajectory, representing a transition into obesity status from childhood to adolescence, was associated with poorer psychosocial health compared to other trajectories.

A study on the dose distributions in various materials from an Ir-192 HDR brachytherapy source.

Dose distributions of (192)Ir HDR brachytherapy in phantoms simulating water, bone, lung tissue, water-lung and bone-lung interfaces using the Monte Carlo codes EGS4, FLUKA and MCNP4C are reported. Experiments were designed to gather point dose measurements to verify the Monte Carlo results using Gafchromic film, radiophotoluminescent glass dosimeter, solid water, bone, and lung phantom. The results for radial dose functions and anisotropy functions in solid water phantom were consistent with previously reported data (Williamson and Li). The radial dose functions in bone were affected more by depth than those in water. Dose differences between homogeneous solid water phantoms and solid water-lung interfaces ranged from 0.6% to 14.4%. The range between homogeneous bone phantoms and bone-lung interfaces was 4.1% to 15.7%. These results support the understanding in dose distribution differences in water, bone, lung, and their interfaces. Our conclusion is that clinical parameters did not provide dose calculation accuracy for different materials, thus suggesting that dose calculation of HDR treatment planning systems should take into account material density to improve overall treatment quality.

Parallel Development of Risk Behaviors in Adolescence: Potential Pathways to Co-occurrence.

This study used data from 5,382 adolescents from the 1997 U.S. National Longitudinal Survey of Youth (NLSY97) to investigate developmental pathways of alcohol use, marijuana use, sexual risk behaviors, and delinquency across ages 14 to 20, examine interrelationships among these risk behaviors across adolescence, and evaluate association between risk behavior trajectories and depressive symptoms in adolescence. Group-based dual trajectory modeling, examining trajectories of two outcomes over time, revealed strong interrelationships among developmental trajectories of the four risk behaviors, and indicated potential pathways to co-occurring risk behaviors. Adolescents with higher levels of alcohol use or marijuana use were more likely to engage in higher levels of early sexual risk-taking and delinquency. Moreover, adolescents involved in higher levels of delinquency were at higher risk for engaging in early sexual risk-taking. Also belonging to the highest risk trajectory of any of the four risk behaviors was positively associated with depressive symptoms in adolescence.

Developmental trajectory of sexual risk behaviors from adolescence to young adulthood.

This study examined the trajectories of sexual risk behaviors among adolescents from ages 15 to 23, and factors associated with those trajectories. The sample was 5,419 adolescents from the 1997 National Longitudinal Survey of Youth. Using group-based trajectory modeling, five distinctive trajectory groups were identified. The High group had a high and increased risk trajectory over the observed ages. The Decreased group had a risk trajectory that accelerated before age 19, but decreased afterwards. The risk trajectories of the Increased-Early and Increased-Late groups were low at age 15, but increased significantly starting at ages 16 and 18 for the groups, respectively. Participants in the Low group remained at low risk over time. Sexual risk behaviors were also positively associated with alcohol use, marijuana use, and delinquency. Results highlight the need for intervention efforts to consider developmental timing of sexual risk behaviors and their associations with other problem behaviors.

Parental Monitoring During Early Adolescence Deters Adolescent Sexual Initiation: Discrete-Time Survival Mixture Analysis.

We used discrete-time survival mixture modeling to examine 5,305 adolescents from the 1997 National Longitudinal Survey of Youth regarding the impact of parental monitoring during early adolescence (ages 14-16) on initiation of sexual intercourse and problem behavior engagement (ages 14-23). Four distinctive parental-monitoring groups were identified and labeled as "High," "Increasing," "Decreasing," and "Low". About 68% of adolescents received a high level of parental monitoring from ages 14 to 16 (High), 6 and 9% respectively exhibited an accelerated (Increasing) and a decelerated trajectory (Decreasing), and 17% had consistently low parental monitoring (Low). Relative to participants in the Low group, adolescents in the High group delayed sexual initiation by 1.5 years. Males, relative to females, were more likely to have had a low trajectory of parental monitoring, and were more likely to initiate sexual intercourse before age 14. In contrast to White Adolescents, Hispanics and Blacks were less likely to receive High parental monitoring, and had a higher rate of early sexual initiation before age 14. The study demonstrates the temporal relationship of parental monitoring with adolescent sexual initiation from a longitudinal perspective. An increase of parental monitoring across ages is accompanied with a decrease of sexual risk. The continual high level of parental monitoring from ages 14 to 16 also mitigated the risk of engagement in substance use and delinquent behaviors from ages 14 to 23.

Employment Trajectories: Exploring Gender Differences and Impacts of Drug Use.

This study investigated the impact of drug use on employment over 20 years among men and women, utilizing data on 7,661 participants in the National Longitudinal Survey of Youth. Growth mixture modeling was applied, and five distinct employment trajectory groups were identified for both men and women. The identified patterns were largely similar for men and women except that a U-shape employment trajectory was uniquely identified for women. Early-initiation drug users, users of "hard" drugs, and frequent drug users were more likely to demonstrate consistently low levels of employment, and the negative relationship between drug use and employment was more apparent among men than women. Also, positive associations between employment and marriage became more salient for men over time, as did negative associations between employment and childrearing among women. Processes are dynamic and complex, suggesting that throughout the life course, protective factors that reduce the risk of employment problems emerge and change, as do critical periods for maximizing the impact of drug prevention and intervention efforts.

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma.

BACKGROUND: To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). METHODS: Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46-54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30<30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram. RESULTS: HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively. CONCLUSION: Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.

Clinical application of radiophotoluminescent glass dosimeter for dose verification of prostate HDR procedure.

High dose rate brachytherapy (HDR-BT) is one of the many modalities for prostate cancer treatment. Due to the nature of HDR-BT, in vivo dosimetry is feasible and can be used to verify consistent dose delivery. In order to validate a dose verification system for HDR-BT prostate cancer treatment, a radiophotoluminescent glass dosimeter (RPLGD) was used and the measurements were compared with those from a thermoluminescent dosimeter. The RPLGD shows many advantages in HDR-BT dose measurement, such as repeatability, stability, and small effective size. These advantages make the RPLGD a superior option for use as a dosimeter in HDR-BT. The results described here show that the difference between the measured dose and the treatment planned dose is less than 5%. A Monte Carlo simulation for the dose was performed using Monte Carlo N -particle to investigate position error. This study concludes that the RPLGD is a promising and reliable dosimeter for HDR-BT in vivo dosimetry with clinically acceptable accuracy.

Unique role of proximal rectal dose in late rectal complications for patients with cervical cancer undergoing high-dose-rate intracavitary brachytherapy.

PURPOSE: To investigate the correlation of the radiation dose to the upper rectum, proximal to the International Commission of Radiation Units and Measurements (ICRU) rectal point, with late rectal complications in patients treated with external beam radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary brachytherapy (ICRT) for carcinoma of the uterine cervix. METHODS AND MATERIALS: Between June 1997 and February 2001, 75 patients with cervical carcinoma completed definitive or preoperative RT and were retrospectively reviewed. Of the 75 patients, 62 with complete dosimetric data and a minimal follow-up of at least 1 year were included in this analysis. Of the 62 patients, 36 (58%) also received concurrent chemotherapy, mainly with cisplatin during EBRT. EBRT consisted of a mean of 50.1 +/- 1.3 Gy of 18-MV photons to the pelvis. A parametrial boost was given to 55 patients. Central shielding was used after 40-45 Gy of pelvic RT. HDR ICRT followed EBRT, with a median dose of 5 Gy/fraction given twice weekly for a median of four fractions. The mean dose to point A from HDR ICRT was 23.9 +/- 3.0 Gy. In addition to the placement of a rectal tube with a lead wire during ICRT, 30-40 mL of contrast medium was instilled into the rectum to demonstrate the anterior rectal wall up to the rectosigmoid junction. Late rectal complications were recorded according to the Radiation Therapy Oncology Group grading system. The maximal rectal dose taken along the rectum from the anal verge to the rectosigmoid junction and the ICRU rectal dose were calculated. Statistical tests were used for the correlation of Grade 2 or greater rectal complications with patient-related variables and dosimetric factors. Correlations among the point A dose, ICRU rectal dose, and maximal proximal rectal dose were analyzed. RESULTS: Fourteen patients (23%) developed Grade 2 or greater rectal complications. Patient-related factors, definitive or preoperative RT, and the use of concurrent chemotherapy were not associated with the occurrence of rectal complications. The maximal rectal dose during ICRT was at the proximal rectum rather than at the ICRU rectal point in 55 (89%) of 62 patients. Patients with Grade 2 or greater rectal complications had received a significantly greater total maximal proximal rectal dose from ICRT (25.6 Gy vs. 19.2 Gy, p = 0.019) and had a greater maximal proximal rectal dose/point A dose ratio (1.025 vs. 0.813, p = 0.024). In contrast, patients with and without rectal complications had a similar dose at point A (25.0 Gy vs.23.6 Gy, p = 0.107). The differences in the ICRU rectal dose (17.8 Gy vs.15.4 Gy, p = 0.065) and the ICRU rectal dose/point A dose ratio (0.71 vs. 0.66, p = 0.210) did not reach statistical significance. Patients with >62 Gy of a direct dose sum from EBRT and ICRT to the proximal rectum (12 of 29 vs. 2 of 33, p = 0.001) and >110 Gy of a total maximal proximal rectal biologic effective dose (13 of 40 vs. 1 of 22, p = 0.012) presented with a significantly increased frequency of Grade 2 or greater rectal complications. The correlations between the maximal proximal rectal dose and the ICRU rectal dose were less satisfactory (Pearson coefficient 0.375). Moreover, 11 of the 14 patients with rectal complications had colonoscopic findings of radiation colitis at the proximal rectum, the area with the maximal rectal dose. CONCLUSION: Eighty-nine percent of our patients had a maximal rectal dose from ICRT at the proximal rectum instead of the ICRU rectal point. The difference between patients with and without late rectal complications was more prominent for the proximal rectal dose than for the ICRU rectal dose. It is important and useful to contrast the whole rectal wall up to the rectosigmoid junction and to calculate the dose at the proximal rectum for patients undergoing HDR ICRT.