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.

"I wanted to close the chapter completely and I feel like that [carrying naloxone] would keep it open a little bit": Refusal to carry naloxone among newly-abstinent opioid users and 12-step identity.

BACKGROUND: 12-step programs aim to address drug-related harms, like opioid overdose, via abstinence. However, abstaining from opioids can diminish tolerance, which increases risk for overdose death upon resumption. A recent study found that desire to abstain from drugs inhibited willingness to participate in take-home naloxone programming, which was linked to perceptions of harm reduction strategies being tied to drug use. In the present study, we uncovered a similar phenomenon occurring among newly-abstinent participants who were refusing to carry naloxone. METHODS: This study is an analysis of broader qualitative data collected throughout Southern California among persons who use opioids, including those recently abstinent. Preliminary analysis revealed that those newly abstinent refused to accept naloxone at the end of interviews, and so we began probing about this (N=44). We used thematic analysis and author positionality to explicate the emergent phenomenon and applied social identity theory to conceptualize findings. RESULTS: Mechanisms underlying naloxone refusal included its tie to a drug-using identity that newly-abstinent participants were attempting to retire. Carrying naloxone was also viewed as pointless due to doubt of witnessing an overdose again. Furthermore, the thought of being equipped with naloxone was not believed to be congruent with an abstinent identity, e.g. "me carrying it [naloxone] is making me feel like I'm going to be hanging out with people that are doing it [using drugs]." CONCLUSION: Recent detoxification heightens vulnerability to overdose, which other newly-abstinent peers might be positioned to respond to as bonds are formed through 12-step identity formation. However, naloxone is often refused by this group due to perceived 12-step identity clash. While some treatment spaces distribute naloxone, 12-step identity associated behavioral expectations appear to conflict with this strategy. Reframing these disconnects is essential for expanding the lifesaving naloxone community safety net.

"Generally, you get 86'ed because you're a liability": An application of Integrated Threat Theory to frequently witnessed overdoses and social distancing responses.

While rates of opioid overdose deaths in North American have increased exponentially in recent years, most overdoses are not fatal, especially when witnesses are present and can intervene. Previous research has found that some people who use drugs [PWUDs] trained in overdose response might cut social ties with frequent overdosers, leading to more solitary opioid use and risk of death if someone overdoses alone. To examine the phenomenon of social distancing of people who overdose frequently, we used data from fifty-two in-depth qualitative interviews collected in Southern California with PWUDs who had recently witnessed an opioid overdose. Transcripts were reviewed and coded thematically, using the Integrated Threat Theory (ITT) to conceptualize the observed phenomenon. ITT outlines how realistic and symbolic threats are experienced by a group. We found that while some participants acknowledged the role of adulterated street drugs in overdoses, individualized blame was nonetheless imposed. Accusations of careless drug use practices fostered negative stereotyping towards frequent overdosers. This was attributed to the need to summon 911 for rescue, which often resulted in police dispatch. The intergroup relationship between police and PWUDs is precarious as police pose realistic threats onto PWUDs - such as incarceration, eviction, and manslaughter charges - leading to intragroup anxiety among PWUDs about future overdose events, and labelled frequent overdosers as liabilities. These threats, and inter/intra-group conflict, explained one reason how and why non-fatal overdoses led to social distancing events. People who overdose frequently were also accused of breaking the norm of drug user surreptitiousness; a symbolic threat that endangered the group due to police exposure. Social distancing might dampen exposure to the protective effect of peer-led interventions such as take-home naloxone programs, increasing risk of overdose death. This phenomenon highlights how intergroup dynamics are driving intragroup processes. Suggestions for tailoring public health interventions are discussed.

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.

Hepatitis B virus infection and immunization status in a new generation of injection drug users in San Francisco.

Hepatitis B virus (HBV) infection is common among injection drug users (IDU). Younger IDU, however, may be less susceptible to infection due to the implementation of public health interventions, such as universal immunization programs and syringe exchange programs. To investigate the current epidemiology of HBV infection and control among a new generation of drug users in the United States, we conducted interviews and examined HBV serologic markers in a cross-section of street-recruited IDU under age 30 in San Francisco, CA. Of the 831 persons studied, 21% showed serologic evidence of current or past infection; 22% had isolated antibodies to hepatitis B surface antigen consistent with vaccine-mediated immunity; and 56% had no HBV markers. In multivariate analyses, HBV infection was associated with drug use behaviour in heterosexual males; sexual behaviour in males who have sex with males; and both drug use and sexual behaviour in females. Vaccine-mediated immunity was independently associated with female sex and younger age. In conclusion, HBV transmission persists among young IDU in San Francisco. Few young injectors show evidence of successful immunization and the majority remains susceptible to disease. Until the broad effects of universal vaccination are seen, targeted and innovative approaches to immunizing young IDU in the US are needed to prevent a substantial number of new HBV infections.

The effect of hCG administration five days after insemination on the first service conception rate of anestrous dairy cows.

The aim of this study was to investigate the effect of treating anovulatory anestrous (AA) dairy cows with 1500 IU of hCG IM, 5 d after insemination, on their first service conception rate. A clinical trial was conducted during the 2003/2004 breeding season involving 442 AA dairy cows in six herds. On Day -8, all cows were treated with a progesterone-containing intravaginal device (Cue-Mate). The devices were removed on Day -2, and on Day -1 all cows received an IM injection of 1mg of estradiol benzoate. Cows in the control group (n=220) received no further treatments. Cows in the treatment group (n=222) which had been inseminated on Days 0 or 1 were treated with 1500 IU of hCG IM 5 d after insemination. Blood was collected from 30 cows (15 in each group) on Days 5 and 12 after AI for analysis of plasma P4 concentration. There was no difference in first service conception rates between the control and treatment groups (46.3% versus 43.6%, respectively; P=0.68), despite the fact that plasma P4 concentrations were higher in the treatment group on Day 12 (4.9+/-1.3 ng/mL versus 6.2+/-2.7 ng/mL for control and treatment groups, respectively; P<0.01). In conclusion, 1500 IU of hCG 5 d after insemination did not improve first service conception rate in AA dairy cows.

Reproductive performance in anestrous dairy cows following treatment with two protocols and two doses of progesterone.

The objectives of this study were to evaluate the effect using two doses of progesterone (P4) releasing devices in two different programs on reproductive performance of anestrous dairy cows. Cows (n = 1555) not detected in estrus by 10 d before the planned start of the seasonal breeding program and in which no CL was palpable were treated with an intravaginal P4-releasing device ('Single'; approximately 1.56 g of P4) or a modified device with triple the normal P4 dose ('Triple'; approximately 4.7 g of P4). The devices were in place for either 6 d ('Short') or 8 d ('Long'), with 1mg estradiol benzoate (EB) given 24 h after device removal. The 'Long' program also included treatment with 2 mg EB at device insertion. The Long program resulted in a higher first service conception rate (RR = 1.18 (95% CI = 1.03-1.33); P = 0.02), but had no effect on the 28-d, 56-d or final pregnancy rate compared to the Short program. There were no effects of dose of P4 on any outcome. In conclusion, the Long compared to the Short program, but not the dose of P4, improved first service conception rates in anestrous cows.

Supplementing previously treated anestrous dairy cows with progesterone does not increase first-service conception rate.

The objective of this study was to investigate the effect of supplementing previously treated anovulatory anestrous (AA) dairy cows with progesterone delivered intra-vaginally for 7 days, commencing 4 or 5 days after insemination, on first-service conception rate. A clinical trial, involving 990 AA dairy cows in 14 dairy herds, was conducted during the 2002/2003 breeding season. On Day -8, all cows were treated with a progesterone-containing intravaginal device (Cue-Mate). The devices were removed on Day -2; on Day -1, all cows were given 1mg of estradiol benzoate im. Cows in the control group (n = 499) received no further treatments. Cows in the treatment group (n = 491) that had been inseminated on Day 0 or 1 had a new device inserted (on Day 4 or 5), with removal of the device after 7 days. First-service conception rates for the control and treatment groups were not different (35.0% versus 36.7% respectively; P = 0.41). Furthermore, there was no difference in conception rates between cows that had devices inserted on Day 4 or 5 (31.3% versus 37.2% respectively; P = 0.45). In conclusion, supplementation of previously treated AA dairy cows with an intravaginal progesterone-releasing device for 7 days (commencing 4 or 5 days after insemination) did not significantly improve first-service conception rate.

Prostate specific antigen inhibits immune responses in vitro: a potential role in prostate cancer.

PURPOSE: Prostate specific antigen (PSA) is found in high concentration in prostate tissue and in semen, in which its physiological function appears to be liquefaction. In prostate cancer the peripheral PSA concentration is elevated, which may be used as a disease marker. Systemic and local immune defects have been demonstrated in prostate cancer and we postulated a role for PSA in this immunosuppression. We explored the effects of PSA on human T-lymphocyte proliferation in vitro. MATERIALS AND METHODS: PSA was purified from normal seminal plasma using a modified chromatographic technique. The effect of PSA or control protein on lymphocyte responses to mitogens, tetanus toxoid and alloantigens was tested. The inhibitory effect observed was further explored by varying the time of PSA addition, denaturing PSA and including interleukin-2 and anti-PSA antibodies. RESULTS: PSA suppressed in vitro phytohemagglutinin and alloantigen stimulated lymphocyte proliferation in a dose dependent manner. This effect was reversed by adding anti-PSA antibodies but not by interleukin-2. CONCLUSIONS: These in vitro PSA effects suggest another T-lymphocyte mediated immunosuppressive mechanism. In vivo high levels of PSA may compromise natural immune responses to cancer and current attempts at immunotherapy for prostate cancer.

CD1a dendritic cells predominate in transitional cell carcinoma of bladder and kidney but are minimally activated.

PURPOSE: In this study, we employed similar techniques to detail dendritic cell subsets within bladder transitional cell carcinoma and kidney transitional cell carcinoma. MATERIALS AND METHODS: To identify both the CD1a+ and CD1a- antigen-expressing dendritic cell populations we employed a double labeling technique to identify non-lineage-expressing leukocytes similar to that employed to isolate blood dendritic cells. RESULTS: Dendritic cells were found in significant numbers within both bladder and kidney derived transitional cell carcinoma. Almost all the dendritic cells among the tumor cells belonged to the CD1a+ subset of epithelial dendritic cells. Similar numbers of dendritic cells were observed in the lamina propria adjacent to the tumor. These dendritic cells belonged predominantly to the CD1a- subset. These differences appear to reflect the different dendritic cell phenotypes reported for the epidermis and dermis. CONCLUSIONS: The number of dendritic cells increased as the grade of the tumor increased, reflecting an overall higher leukocyte density in higher grade tumors. However, a possible trend for less dendritic cell activation in higher grade cancers was noted, raising the intriguing possibility that this might be a relevant prognostic factor, to be confirmed in a larger study.

Microvessel density as a prognostic marker for transitional cell carcinoma of the bladder.

OBJECTIVE: To investigate the prognostic significance of mean vascular density (MVD) in a variety of transitional cell carcinomas (TCC) obtained by biopsy and cystectomy, and thus determine the importance of vascular density as a prognostic indicator for vesical TCC. PATIENTS AND METHODS: Tumour vasculature was visualized using factor VIII immunohistochemistry. The MVDs of tumours from 42 cystectomy specimens were correlated with patient survival over a maximum follow-up of 156 months. The results were also compared with those obtained from initial bladder biopsy in a subset of 29 patients. RESULTS: Twenty-five patients had died over a mean follow-up of 32 months. The MVDs from cystectomy specimens ranged from 29 to 229 vessels per medium-power field (0.94 mm2) while that for biopsies before cystectomy ranged from 51 to 155 vessels. The MVD for both cystectomy and biopsy specimens showed a significant association with survival, but this was absent in a multivariate analysis that included tumour stage and grade, and there was a poor correlation between the MVD of cystectomy- and biopsy-derived tumours. CONCLUSION: The assessment of tumour vascularity appears to be of little clinical importance for vesical TCC.

Minimal recruitment and activation of dendritic cells within renal cell carcinoma.

Dendritic cells (DCs) are predicted to participate in natural tumor immunity by migrating into tumors, where they acquire antigen, undergo activation, and migrate to lymph nodes to initiate a T-lymphocyte response against tumor-associated antigens. The presence of DCs using defined lineage markers and their function in human tumors has not been assessed previously. The monoclonal antibodies against CMRF-44 and CD83, which are differentiation/activation antigens on DCs, were used in immunohistological and flow cytometry studies to analyze the DC subtypes infiltrating 14 cases of human renal cell carcinoma (RCC). The functional immunocompetence of the DCs isolated from RCC was assessed by testing their ability to stimulate an allogeneic mixed leukocyte reaction. The majority of leukocytes present within the RCC were macrophages (62% +/- 14.7) or T lymphocytes (19% +/- 9.5), with CD45+ HLA-DR+ lineage-negative putative DCs accounting for less than 10% of the leukocytes present. Of these, a subset, comprising less than 1% of total leukocytes, had an activated CMRF-44+ or CD83+ DC phenotype. Activated CMRF-44+ and CD83+ DCs were more evident outside the tumor in association with T-lymphocyte clusters. The number of CMRF-44+ DCs correlated closely with the number of S-100-positive DCs. Isolation of DCs from eight RCCs was achieved, and flow cytometry studies confirmed the small proportion of activated CMRF-44+ DCs. The CMRF-44+ DCs stimulated an allogeneic mixed leukocyte reaction, but the CMRF-44- DCs (normal tissue DC precursors and other cells) failed to do so. These results suggest that RCCs recruit few DCs into the tumor substance, and the tumor environment fails to initiate the expected protective activation of DCs. These two mechanisms, amongst others, may contribute to tumor escape from immunosurveillance. In vitro loading of DCs with tumor-associated antigens may be a useful therapeutic maneuver.

Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone.

Hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) was formulated in a metered-dose inhaler (MDI) to deliver a particle size of 1.1 microm compared with 35 microns for currently marketed chlorofluorocarbon (CFC)-BDP products. Two phase I single-dose human deposition studies were conducted using technetium 99m-radiolabelled BDP in a press-and-breathe actuator without an add-on spacer. A healthy volunteer study (n=6) showed that 55-60% of the HFA-BDP ex-actuator dose was deposited in the lungs, with 29-30% deposited in the oropharynx. CFC-BDP deposition was 4-7% in the lungs and 90-94% in the oropharynx. The pattern of deposition within the lung showed that HFA-BDP was spread diffusely throughout the lung airways, whereas CFC-BDP was confined to the central airways with little, if any, peripheral airway deposition. A second study with asthmatics (n=16) confirmed that 56% of the HFA-BDP dose was deposited in the airways, with 33% in the oropharynx. In conclusion, hydrofluoroalkane-134a-beclomethasone dipropionate deposition was much greater in the airways than chlorofluorocarbon-beclomethasone dipropionate, with a concomitant reduction in oropharyngeal deposition. The increased lung deposition efficiency of the hydrofluoroalkane propellant has led to a reduction in the amount of beclomethasone dipropionate needed to achieve a similar efficacy. The penetration of the hydrofluoroalkane to the small airways may provide asthma treatment not afforded by conventional chlorofluorocarbons.

Is intravenous lidocaine an effective adjuvant for endotracheal intubation in children undergoing induction of anesthesia with halothane-nitrous oxide?

STUDY OBJECTIVE: To evaluate the efficacy of intravenous (i.v.) lidocaine in suppressing the cough reflex and increases in intraocular pressure (IOP), heart rate (HR), and mean arterial pressure (MAP) elicited by endotracheal intubation. DESIGN: Prospective, randomized, placebo-controlled, blinded study. PATIENTS: 60 ASA physical status 1 premedicated children aged 2 to 6 years undergoing induction of anesthesia with halothane-nitrous oxide (N2O) for surgery to correct strabismus. INTERVENTIONS: Patients were randomly divided into two groups of 30 each. The control group (C) received saline and the treatment group (L) received 2 mg/kg i.v. lidocaine 90 seconds prior to endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: Awake HR and MAP; IOP, HR, and MAP 45 seconds prior to endotracheal intubation, immediately after endotracheal intubation, and 1 minute later, were recorded. Coughing was noted at endotracheal intubation. Lidocaine prevented coughing and a significant increase in IOP. Although significant increases in HR and MAP were observed in both groups (comparing preintubation and postintubation values), these increases were significantly less in the L group compared with the C group. CONCLUSIONS: In healthy premedicated children, aged 2 to 6 years, who are undergoing induction of anesthesia with halothane-N2O, 2 mg/kg of lidocaine given 90 seconds prior to laryngoscopy effectively suppresses the cough reflex and increase in IOP secondary to endotracheal intubation and attenuates increases in HR and MAP.

The role of laparoscopy in evaluation of the impalpable undescended testis.

BACKGROUND: The evaluation and management of the impalpable testis remains controversial. The authors' experience with laparoscopy for the treatment of this condition is reported here. METHODS: All children with impalpable testes underwent an examination under anaesthetic and if negative, a laparoscopy was performed to locate the testis. A prospective evaluation was undertaken to determine the success and morbidity of this approach. RESULTS: Thirty-six children (median age 2.5 years) underwent laparoscopy to localize 40 impalpable testes. In 32 patients with unilateral impalpable testis, 10 were intra-abdominal, nine were absent. In 13 patients, the vas and vessels entered the groin, and in 12 of these a small testis remnant was excised and in the other a normal-looking testis was brought down. In four patients with bilateral impalpable testes, one testis was absent, three testes were intra-abdominal and four were small testis remnants in the groin. The average laparoscopy time was 15 min, and 34 of 36 children were operated on as day-stay cases. One child had an omental hernia via a port site. CONCLUSION: Laparoscopy is safe and effective at localizing impalpable testes in children and can be performed as day-stay procedures in the majority of cases.

Radical prostatectomy: prospective assessment of mortality and morbidity.

OBJECTIVE: To prospectively analyse the morbidity of radical prostatectomy. METHODS: Morbidity data from 188 consecutive radical prostatectomy patients were collected prospectively. Mortality, intraoperative, early postoperative and late postoperative complications were analysed. RESULTS: 1.5% mortality. 3.7% suffered an intraoperative complication. Early postoperative problems were common (43%). Of those with greater than 1 year follow-up, 5.9% remained with some incontinence, and a further 11 patients had artificial sphincters implanted; 32% had narrowing of the anastomosis, requiring at least 1 dilation; 43% of patients retained their potency. CONCLUSIONS: It is concluded that radical prostatectomy can be performed with minimal mortality and acceptable morbidity.

Progression in untreated carcinoma of the prostate metastatic to regional lymph nodes (stage t0 to 4,N1 to 3.M0,D1). European Organization for Research and Treatment of Cancer Genitourinary Group.

PURPOSE: We attempt to contribute to the understanding of the natural history of prostate cancer metastatic to lymph nodes. MATERIALS AND METHODS: A total of 61 patients with node-positive prostate cancer was prospectively followed without adjuvant treatment for an average of 41 months. The impact of T and P categories, grade, tumor volume and prostate specific antigen change on interval to progression was studied in a univariate and multivariate analysis. RESULTS: Median interval to progression was 18 months, and correlated with grade and prostate specific antigen doubling time. Changes in prostatic volume with time were not predictive. CONCLUSIONS: Our study provides insight into the natural history of node-positive disease and identifies relevant prognostic factors that may be used for treatment decisions.

Radical prostatectomy as a monotherapy for locally advanced (stage T3) prostate cancer.

Within a prospective protocol initiated in 1977, 100 patients with locally extensive prostate cancer (stage T3, 1982 tumor, nodes and metastasis classification) were treated by pelvic node dissection and radical prostatectomy as monotherapy. Adjuvant treatment was not given until disease progression. Radical prostatectomy, except for 3 young patients with a single micrometastasis, was not done if positive lymph nodes were found at frozen section. Six patients had positive lymph nodes at permanent sections but not at frozen section. Average followup was 43.9 months (range 1 to 155 months). Histological grade was determined according to the Mostofi system. Progression was determined biochemically (prostate specific antigen elevation) and clinically by evidence of metastatic disease, either histologically proved or evidenced as new hot spots on bone scan or chest x-rays. Of the 100 patients 41 did not undergo radical prostatectomy: 39 because of positive lymph nodes and 2 because of evidence of a stage pT4 tumor at surgical exploration. Of those 59 patients who underwent radical prostatectomy 9 had positive lymph nodes, while 2 had stage pT4, 39 stage pT3 and 9 stage pT2 tumors. Only 1 of the 9 patients with lymph node metastases is free of biochemical or clinical progression. Disease also progressed in both stage pT4, 27 of 39 stage pT3 and none of the 9 stage pT2 cases. A total of 22 patients was free of clinical or biochemical progression. Clinical progression was evidenced in approximately half of the cases as distant and local progression. Data on stage T3 disease were compared to those of 129 patients with stages T0 to T2 disease. There was a significant difference in interval to clinical progression for these 2 groups (p = 0.001). However, if grade 3 cases were excluded from the stage T3 group, this difference disappeared. Prognostic factors analyzed were pretreatment and posttreatment grade, pretreatment prostate specific antigen and prostatic acid phosphatase levels, positive margins, seminal vesicle invasion and nodal status. The analysis allows one to identify groups of patients who may benefit and others who certainly do not benefit from radical prostatectomy in this disease category. In the latter group effective adjuvant treatment is urgently indicated.