Spatial proximity and access to buprenorphine or methadone treatment for opioid use disorder in a sample of people misusing opioids in Southern California.

BACKGROUND: In response to the opioid crisis, over the last 10 years substantial strides have been made to increase the availability of evidence-based treatments for opioid use disorder, in particular buprenorphine maintenance, in the United States. Despite these worthwhile efforts, uptake rates of evidence-based treatment remain relatively low. As part of a broader study of opioid misuse, we examined proximity to evidence-based treatment as a potential barrier to treatment access. METHODS: In 2017-2018, we surveyed 218 individuals misusing prescription opioids or using street opioids in three Southern Californian counties. The study calculated driving distance from place of residence to the closest treatment provider offering buprenorphine or methadone treatment for opioid use disorders. RESULTS: Median distance to providers was 3.8 km (2.4 miles). Seventy one (33%) participants had received some form of treatment in the last 3 months; however, only 26 (40%) of these had received buprenorphine or methadone maintenance treatment. Participants receiving treatment at the time of their interview were traveling an average 16.8 km (10.4 miles) to reach treatment, indicating that as a group this population was both willing and able to seek and engage with treatment. CONCLUSIONS: In the suburban and exurban communities in which our study was based, our findings suggest that simple physical proximity to providers of evidence-based treatment for opioid use disorder is no longer a critical barrier. Other barriers to uptake of buprenorphine or methadone maintenance treatment clearly remain and need to be addressed. DISCLAIMER: Findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Transitioning from pharmaceutical opioids: A discrete-time survival analysis of heroin initiation in suburban/exurban communities.

INTRODUCTION: Research identifying pathways to heroin use has typically been conducted among urban populations. This study examined heroin initiation following pharmaceutical opioid use in three suburban/exurban Southern California counties. METHODS: Interviewer-administered surveys collected data among 330 participants (65.9 % male; 63.9 % non-Hispanic white) whose initial use of any opioid was a pharmaceutical opioid. Retrospective discrete-time survival analysis identified predictors of heroin initiation, measured as self-reported age of first heroin use. RESULTS: Median age of first pharmaceutical opioid use was 17 years; 50.6 % initially acquired pharmaceutical opioids from an illicit source, 56.7 % first used pharmaceutical opioids for recreational purposes, and 86 % initiated heroin use. Average time from first pharmaceutical opioid use to first heroin use was 8.2 years. Drug/alcohol treatment (adjusted Hazard Ratio [aHR]: 0.67, 95 % CI: 0.50, 0.88) was associated with delayed time to heroin initiation. Obtaining opioids from non-medical sources (aHR: 2.21, 95 % CI: 1.55, 3.14) was associated with accelerated time to heroin initiation. Reporting supply problems with obtaining pharmaceutical opioids (e.g., unable to acquire pharmaceutical opioids) was associated with accelerated time to heroin initiation, but the magnitude of this effect was dependent on one's history of methamphetamine use (p < 0.05). CONCLUSIONS: Time to heroin initiation following pharmaceutical opioid use was accelerated among those reporting supply problems and delayed among those with exposure to substance use treatment. Interventions interrupting supply of opioids might benefit from coordination with evidence-based medication-assisted treatment to minimize the risk of transitioning to heroin use, particularly among those with a long history of non-prescribed pharmaceutical opioid use.

The law on the streets: Evaluating the impact of Mexico's drug decriminalization reform on drug possession arrests in Tijuana, Mexico.

BACKGROUND: In 2009, Mexican Federal Government enacted "narcomenudeo" reforms decriminalizing possession of small amounts of drugs, delegating prosecution of retail drug sales to the state courts, and mandating treatment diversion for habitual drug users. There has been insufficient effort to formally assess the decriminalization policy's population-level impact, despite mounting interest in analagous reforms across the globe. METHODS: Using a dataset of municipal police incident reports, we examined patterns of drug possession, and violent and non-violent crime arrests between January 2009 and December 2014. A hierarchical panel data analysis with random effects was conducted to assess the impact of narcomenudeo's drug decriminalization provision. RESULTS: The reforms had no significant impact on the number of drug possession or violent crime arrests, after controlling for other variables (e.g. time trends, electoral cycles, and precinct-level socioeconomic factors). Time periods directly preceding local elections were observed to be statistically associated with elevated arrest volume. CONCLUSIONS: Analysis of police statistics parallel prior findings that Mexico's reform decriminalizing small amounts of drugs does not appear to have significantly shifted drug law enforcement in Tijuana. More research is required to fully understand the policy transformation process for drug decriminalization and other structural interventions in Mexico and similar regional and international efforts. Observed relationship between policing and political cycles echo associations in other settings whereby law-and-order activities increase during mayoral electoral campaigns.

Deletion of UCP1 enhances ex vivo aortic vasomotor function in female but not male mice despite similar susceptibility to metabolic dysfunction.

Females are typically more insulin sensitive than males, which may be partly attributed to greater brown adipose tissue (BAT) activity and uncoupling protein 1 (UCP1) content. Accordingly, we tested the hypothesis that UCP1 deletion would abolish sex differences in insulin sensitivity and that whitening of thoracic periaortic BAT caused by UCP1 loss would be accompanied with impaired thoracic aortic function. Furthermore, because UCP1 exerts antioxidant effects, we examined whether UCP1 deficiency-induced metabolic dysfunction was mediated by oxidative stress. Compared with males, female mice had lower HOMA- and AT-insulin resistance (IR) despite no significant differences in BAT UCP1 content. UCP1 ablation increased HOMA-IR, AT-IR, and whitening of BAT in both sexes. Expression of UCP1 in thoracic aorta was greater in wild-type females compared with males. Importantly, deletion of UCP1 enhanced aortic vasomotor function in females only. UCP1 ablation did not promote oxidative stress in interscapular BAT. Furthermore, daily administration of the free radical scavenger tempol for 8 wk did not abrogate UCP1 deficiency-induced increases in adiposity, hyperinsulinemia, or liver steatosis. Collectively, we report that 1) in normal chow-fed mice housed at 25°C, aortic UCP1 content was greater in females than males and its deletion improved ex vivo aortic vasomotor function in females only; 2) constitutive UCP1 content in BAT was similar between females and males and loss of UCP1 did not abolish sex differences in insulin sensitivity; and 3) the metabolic disruptions caused by UCP1 ablation did not appear to be contingent upon increased oxidative stress in mice under normal dietary conditions.

Loss of UCP1 exacerbates Western diet-induced glycemic dysregulation independent of changes in body weight in female mice.

We tested the hypothesis that female mice null for uncoupling protein 1 (UCP1) would have increased susceptibility to Western diet-induced "whitening" of brown adipose tissue (AT) and glucose intolerance. Six-week-old C57BL/6J wild-type (WT) and UCP1 knockout (UCP1-/-) mice, housed at 25°C, were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 28 wk. Loss of UCP1 had no effect on energy intake, energy expenditure, spontaneous physical activity, weight gain, or visceral white AT mass. Despite similar susceptibility to weight gain compared with WT, UCP1-/- exhibited whitening of brown AT evidenced by a striking ~500% increase in mass and appearance of large unilocular adipocytes, increased expression of genes related to inflammation, immune cell infiltration, and endoplasmic reticulum/oxidative stress (P < 0.05), and decreased mitochondrial subunit protein (COX I, II, III, and IV, P < 0.05), all of which were exacerbated by Western diet (P < 0.05). UCP1-/- mice also developed liver steatosis and glucose intolerance, which was worsened by Western diet. Collectively, these findings demonstrate that loss of UCP1 exacerbates Western diet-induced whitening of brown AT, glucose intolerance, and induces liver steatosis. Notably, the adverse metabolic manifestations of UCP1-/- were independent of changes in body weight, visceral adiposity, and energy expenditure. These novel findings uncover a previously unrecognized metabolic protective role of UCP1 that is independent of its already established role in energy homeostasis.

Retention of sedentary obese visceral white adipose tissue phenotype with intermittent physical activity despite reduced adiposity.

Regular physical activity is effective in reducing visceral white adipose tissue (AT) inflammation and oxidative stress, and these changes are commonly associated with reduced adiposity. However, the impact of multiple periods of physical activity, intercalated by periods of inactivity, i.e., intermittent physical activity, on markers of AT inflammation and oxidative stress is unknown. In the present study, 5-wk-old male C57BL/6 mice were randomized into three groups (n = 10/group): sedentary, regular physical activity, and intermittent physical activity, for 24 wk. All animals were singly housed and fed a diet containing 45% kcal from fat. Regularly active mice had access to voluntary running wheels throughout the study period, whereas intermittently active mice had access to running wheels for 3-wk intervals (i.e., 3 wk on/3 wk off) throughout the study. At death, regular and intermittent physical activity was associated with similar reductions in visceral AT mass (approximately -24%, P < 0.05) relative to sedentary. However, regularly, but not intermittently, active mice exhibited decreased expression of visceral AT genes related to inflammation (e.g., monocyte chemoattractant protein 1), immune cell infiltration (e.g., CD68, CD11c, F4/80, CD11b/CD18), oxidative stress (e.g., p47 phagocyte oxidase), and endoplasmic reticulum stress (e.g., CCAAT enhancer-binding protein homologous protein; all P < 0.05). Furthermore, regular, but not intermittent, physical activity was associated with a trend toward improvement in glucose tolerance (P = 0.059). Collectively, these findings suggest that intermittent physical activity over a prolonged period of time may lead to a reduction in adiposity but with retention of a sedentary obese white AT and metabolic phenotype.

The longitudinal association of venue stability with consistent condom use among female sex workers in two Mexico-USA border cities.

We examined the relationship between venue stability and consistent condom use (CCU) among female sex workers who inject drugs (FSW-IDUs; n = 584) and were enrolled in a behavioural intervention in two Mexico-USA border cities. Using a generalized estimating equation approach stratified by client type and city, we found venue stability affected CCU. In Tijuana, operating primarily indoors was significantly associated with a four-fold increase in the odds of CCU among regular clients (odds ratio [OR]: 3.77, 95% confidence interval [CI]: 1.44, 9.89), and a seven-fold increase among casual clients (OR: 7.18, 95% CI: 2.32, 22.21), relative to FSW-IDUs spending equal time between indoor and outdoor sex work venues. In Ciudad Juarez, the trajectory of CCU increased over time and was highest among those operating primarily indoors. Results from this analysis highlight the importance of considering local mobility, including venue type and venue stability, as these characteristics jointly influence HIV risk behaviours.

Angiosarcoma of the right atrium presenting as syncope and hemorrhagic pericardial tamponade.

Angiosarcoma of the heart is a rare malignancy that can present in many ways. It is an important diagnosis to consider in patients presenting with otherwise unexplained tamponade-type symptoms. Here we present a case of a young male who presented with hemorrhagic tamponade and underwent resection of a large angiosarcoma of the right atrium. In this case, we describe the rare presentation of angiosarcoma with its diagnostic approaches, hospital course, clinical management, and discussion.

Necrotizing pneumococcal pneumonia in childhood.

We describe the rare complication of necrotizing pneumonia and invasive pneumococcal infection in 3 previously healthy pediatric patients. Lobar consolidation and pleural effusions appeared initially, followed within several days by the appearance of multiple small lucencies in the area of consolidation. In one case, necrosis progressed to a large abscess cavity. Surgical intervention was limited to treatment of pleural space complications. There were no deaths. Pulmonary parenchymal residual was limited to a thin-walled cavity in one case.

Spontaneous resolution of a plasma cell granuloma in a 9-year-old.

A previously healthy 9-year-old white boy presented with a 13-lb weight loss over a period of 4 weeks and a 4.5-cm mass in the right lung. Histology was compatible with a plasma cell granuloma, which is the most common benign childhood lung tumor. Surgical management with segmental or wedge resection is the usual standard of care in this situation. However, it has been suggested that with a confirmed histologic diagnosis surgical resection is not warranted. This patient was managed conservatively. Repeat computed tomography scan 6 weeks later revealed significant resolution of the lesion, and at 7 months the lesion had totally resolved. Spontaneous resolution of this lesion has been rarely described in pediatric populations.

Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). I. Multireplicated dose-response studies in four inbred strains and one outbred stock of mice.

A large-scaled multireplicated developmental toxicity study was conducted in various strains/stocks of mice with the herbicide, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), by gavage on Gestational Days 6 through 14. The most important attributes of the study design were replicated test groups, a minimum of four dose levels per replicate, use of multiple stocks/strains of animals to obtain an estimate of the range in sensitivities due to genotype, complete pathological evaluation of maternal animals, and histopathological as well as teratological evaluation of the fetuses. Developmental toxicity was observed at doses below those producing discernible or measurable maternal toxicity. Regression and/or probit analyses were conducted to determine whether a dose-response relationship existed. Reduced fetal weight and increased incidence of cleft palate and embryolethality were the most significant prenatal effects of 2,4,5-T exposure observed in this study. Each strain/stock exhibited a dose-related decrease in fetal weight with the CD-1 mice having the steepest slope and the A/J mice having the shallowest slope. There was a striking similarity among the slopes of the dose-response curves for the various strains/stocks. The mean incidence of embryolethality in the A/J strain was significantly greater than that of the other strains or stocks. There was substantial variation among replicates within strains. The use of the replicated study design was logistically necessary due to the magnitude of the study and it also served to increase the statistical power of the study.

Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). II. Multireplicated dose-response studies with technical and analytical grades of 2,4,5-T in four-way outcross mice.

A series of multireplicated developmental toxicity studies were conducted in four-way outcross mice and CD-1 outbred mice administered either analytical or technical grades of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) by gavage on Gestational Days 6 through 14. The formulations of 2,4,5-T differed by a factor of 10-fold in 2,3,7,8-tetrachlorodibenzo-p-dioxin levels. Reduced fetal weight and increased incidences of cleft palate and embryolethality were the most significant prenatal effects of both formulations of 2,4,5-T observed in all strains/stocks of mice. Both the outcross and outbred mice exhibited a dose-response relationship with each of the above endpoints and the dose-response curves were parallel. There were no embryotoxic or fetotoxic differences between the technical and analytical grades of 2,4,5-T with regard to extent of fetal weight reduction, resorption rate, or cleft palate incidence. There was little difference in the results between the four-way outcross mouse and the CD-1 outbred mouse.

Achievement in an alternative high school for emotionally/behaviorally disturbed students.

Some 1,300 alternative high schools have been established in the United States for dealing with the special education needs of emotionally and behaviorally disturbed youth. The present study investigated cognitive, academic, and psychosocial variables associated with success in an alternative high school for such youth. Results indicated that psychosocial variables (Family Pathology, Duration of Disturbance, and Age of Admission) were associated with success, whereas cognitive and academic variables were not. These results are interpreted in light of their implications for assessment and placement decisions, management by mental health and school professionals, and curriculum modifications necessary for success.

Third-trimester colectomy for severe ulcerative colitis. A case report.

Despite steroid therapy and total parenteral nutrition, a patient with severe ulcerative colitis developed a colon perforation with peritonitis that necessitated colectomy at 28 weeks' gestation. The pregnancy was left intact; the postoperative vaginal delivery was uneventful.

Acute toxicity of pesticides in adult and weanling rats.

LD50 values were determined for 57 pesticides administered by the oral or dermal route to adult male and female Sherman rats. Thirty-six of the chemicals were also tested by the oral route in one sex of weanlings. Nine pesticides tested by the oral route (bufencarb, cacodylic acid, dialifor, deltamethrin, dicamba, diquat, quintozene, phoxim, pyrazon) and four tested by the dermal route (bufencarb, chlordimeform, dichlofenthion, leptophos) were more toxic to females than to males whereas famphur and 2,4,5-T (oral route) were less toxic to females. Eighteen of the test chemicals were more toxic to the adult than to the weanling and four compounds (leptophos, methidathion, pyrazon, and sulfoxide) were more toxic to the weanling. In additional studies the variability of the LD50 value over a 1-year period was examined for two typical insecticides. Six consecutive bimonthly oral LD50 determinations for parathion and DDT in adults of both sexes indicated that the LD50 values were little affected by the time of year that the tests were done.