METHODS: We developed a linear optimisation model to estimate efficiency gains that could be achieved based on current procurement of OAT. We also developed a dynamic, compartmental population model of HIV transmission that included both injection and sexual risk to estimate the effect of OAT scale-up on HIV infections and mortality over a 10-year horizon. The compartmental population model was calibrated to HIV prevalence and incidence among PWID for 23 administrative regions of Ukraine. Sources for regional data included the SyrEx database, the Integrated Biological and Behavioral Survey, the Ukrainian Center for Socially Dangerous Disease Control of the Ministry of Health of Ukraine, the Public Health Center of the Ministry of Health of Ukraine, and the Ukrainian Census.
FINDINGS: Under a status-quo scenario (OAT coverage of 2·7% among PWID), the number of new HIV infections among PWID in Ukraine over the next 10 years was projected to increase to 58 820 (95% CI 47 968-65 535), with striking regional differences. With optimum allocation of OAT without additional increases in procurement, OAT coverage could increase from 2·7% to 3·3% by increasing OAT doses to ensure higher retention levels. OAT scale-up to 10% and 20% over 10 years would, respectively, prevent 4368 (95% CI 3134-5243) and 10 864 (7787-13 038) new HIV infections and reduce deaths by 7096 (95% CI 5078-9160) and 17 863 (12 828-23 062), relative to the status quo. OAT expansion to 20% in five regions of Ukraine with the highest HIV burden would account for 56% of new HIV infections and 49% of deaths prevented over 10 years.
INTERPRETATION: To optimise HIV prevention and treatment goals in Ukraine, OAT must be substantially scaled up in all regions. Increased medication procurement is needed, combined with optimisation of OAT dosing. Restricting OAT scale-up to some regions of Ukraine could benefit many PWID, but the regions most affected are not necessarily those with the highest HIV burden.
FUNDING: National Institute on Drug Abuse.
METHODS: Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT). DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms, including c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), using the allelic discrimination real-time polymerase chain reaction.
RESULTS: A total of 152 participants were recruited in this observational study. Frequencies of mutated allele for c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms were 56.6%, 49.7%, and 43.4%, respectively. Our results revealed an association of the CGC/CGC diplotype (c.1236C>T, c.2677G>T/A, and c.3435C>T) with cold pain sensitivity. Participants with the CGC/CGC diplotype had 90% and 72% higher cold pain thresholds (87.62 seconds vs. 46.19 seconds, P = 0.010) and cold pain tolerances (97.24 seconds vs. 56.54 seconds, P = 0.021), respectively, when compared with those without the diplotype.
CONCLUSION: The CGC/CGC diplotype of ABCB1 polymorphisms was associated with variability in cold pain threshold and pain tolerance in healthy males.
OBJECTIVE: The objective of this study was to determine whether combined total intravenous anesthesia (TIVA) technique with propofol/remifentanil is associated with less SSEP suppression when compared to combined volatile agent desflurane/remifentanil anesthesia during corrective scoliosis surgery at a comparable depth of anesthesia.
DESIGN: It is a randomized controlled trial.
SETTING: The study was conducted at the Single tertiary University Hospital during October 2014 to June 2015.
PATIENTS: Patients who required SSEP and had no neurological deficits, and were of American Society of Anesthesiologist I and II physical status, were included. Patients who had sensory or motor deficits preoperatively and significant cardiovascular and respiratory disease were excluded. A total of 72 patients were screened, and 67 patients were randomized and allocated to two groups: 34 in desflurane/remifentanil group and 33 in TIVA group. Four patients from desflurane/remifentanil group and three from TIVA group were withdrawn due to decrease in SSEP amplitude to <0.3 µV after induction of anesthesia. Thirty patients from each group were analyzed.
INTERVENTIONS: Sixty-seven patients were randomized to receive TIVA or desflurane/remifentanil anesthesia.
MAIN OUTCOME MEASURES: The measurements taken were the amplitude and latency of SSEP monitoring at five different time points during surgery: before and after the induction of anesthesia, at skin incision, at pedicle screw insertion, and at rod insertion.
RESULTS: Both anesthesia techniques, TIVA and desflurane/remifentanil, resulted in decreased amplitude and increased latencies of both cervical and cortical peaks. The desflurane/remifentanil group had a significantly greater reduction in the amplitude ( p = 0.004) and an increase in latency ( p = 0.002) of P40 compared with the TIVA group. However, there were no differences in both amplitude ( p = 0.214) and latency ( p = 0.16) in cervical SSEP between the two groups.
CONCLUSIONS: Compared with TIVA technique, desflurane/remifentanil anesthesia caused more suppression in cortical SSEP, but not in cervical SSEP, at a comparable depth of anesthesia.
METHODS: We did a parallel, two-arm, prospective observational study of opioid-dependent individuals aged 18 years and older who were treated in Malaysia in the Klang Valley in two settings: CDDCs and VTCs. We used sequential sampling to recruit individuals. Assessed individuals in CDDCs were required to participate in services such as counselling sessions and manual labour. Assessed individuals in VTCs could voluntarily access many of the components available in CDDCs, in addition to methadone therapy. We undertook urinary drug tests and behavioural interviews to assess individuals at baseline and at 1, 3, 6, 9, and 12 months post-release. The primary outcome was time to opioid relapse post-release in the community confirmed by urinary drug testing in individuals who had undergone baseline interviewing and at least one urine drug test (our analytic sample). Relapse rates between the groups were compared using time-to-event methods. This study is registered at ClinicalTrials.gov (NCT02698098).
FINDINGS: Between July 17, 2012, and August 21, 2014, we screened 168 CDDC attendees and 113 VTC inpatients; of these, 89 from CDDCs and 95 from VTCs were included in our analytic sample. The baseline characteristics of the two groups were similar. In unadjusted analyses, CDDC participants had significantly more rapid relapse to opioid use post-release compared with VTC participants (median time to relapse 31 days [IQR 26-32] vs 352 days [256-unestimable], log rank test, p<0·0001). VTC participants had an 84% (95% CI 75-90) decreased risk of opioid relapse after adjustment for control variables and inverse propensity of treatment weights. Time-varying effect modelling revealed the largest hazard ratio reduction, at 91% (95% CI 83-96), occurs during the first 50 days in the community.
INTERPRETATION: Opioid-dependent individuals in CDDCs are significantly more likely to relapse to opioid use after release, and sooner, than those treated with evidence-based treatments such as methadone, suggesting that CDDCs have no role in the treatment of opioid-use disorders.
FUNDING: The World Bank Group, Doris Duke Charitable Foundation, National Institute on Drug Abuse, Australian National Health & Medical Research Council, National Institute of Mental Health, and the University of Malaya-Malaysian Ministry of Higher Education High Impact Research Grant.
METHODS: After institutional approval and written informed consent, patients received a brief remifentanil infusion during continuous monitoring of ventilation. We compared minute ventilation in 30 patients with moderate-to-severe obstructive sleep apnea diagnosed by polysomnography and 20 controls with no to mild obstructive sleep apnea per polysomnography. Effect site concentrations were estimated by a published pharmacologic model. We modeled minute ventilation as a function of effect site concentration and the estimated carbon dioxide. Obstructive sleep apnea status, body mass index, sex, age, use of continuous positive airway pressure, apnea/hypopnea events per hour of sleep, and minimum nocturnal oxygen saturation measured by pulse oximetry in polysomnography were tested as covariates for remifentanil effect site concentration at half-maximal depression of minute ventilation (Ce50) and included in the model if a threshold of 6.63 (P < 0.01) in the reduction of objective function was reached and improved model fit.
RESULTS: Our model described the observed minute ventilation with reasonable accuracy (22% median absolute error). We estimated a remifentanil Ce50 of 2.20 ng · ml (95% CI, 2.09 to 2.33). The estimated value for Ce50 was 2.1 ng · ml (95% CI, 1.9 to 2.3) in patients without obstructive sleep apnea and 2.3 ng · ml (95% CI, 2.2 to 2.5) in patients with obstructive sleep apnea, a statistically nonsignificant difference (P = 0.081). None of the tested covariates demonstrated a significant effect on Ce50. Likelihood profiling with the model including obstructive sleep apnea suggested that the effect of obstructive sleep apnea on remifentanil Ce50 was less than 5%.
CONCLUSIONS: Obstructive sleep apnea status, apnea/hypopnea events per hour of sleep, or minimum nocturnal oxygen saturation measured by pulse oximetry did not influence the sensitivity to remifentanil-induced ventilatory depression in awake patients receiving a remifentanil infusion of 0.2 μg · kg of ideal body weight per minute.
DESIGN: This study was designed as a retrospective cohort study.
SETTING AND PARTICIPANTS: In this study, we analysed the prescription databases of tertiary hospitals in Malaysia. This study included patients aged ≥18 years with at least one opioid prescription (buprenorphine, morphine, oxycodone, fentanyl, dihydrocodeine or tramadol) between 1 January 2011 and 31 December 2016. These patients had no opioid prescriptions in the 365 days prior, and were followed up for 365 days after the initial opioid prescription.
MAIN OUTCOME MEASURES: The main outcome measures were the number of short-term (<90 days) and long-term opioid users (≥90 days), initial opioid prescription period and daily dose.
RESULTS: There were 33 752 opioid-naïve patients who received opioid prescriptions (n=43 432 prescriptions) during the study period. Of these, 29 824 (88.36%) were short-term opioid users and 3928 (11.64%) were long-term opioid users. The majority of these short-term (99.09%) and long-term users (96.18%) received an initial daily opioid dose of <50 mg/day with a short-acting opioid formulation. Short-term opioid users were predominantly prescribed opioids for 3-7 days (59.06%) by the emergency department (ED, 60.56%), while long-term opioid users were primarily prescribed opioids for ≥7 days (91.85%) by non-ED hospital departments (91.8%). The adjusted model showed that the following were associated with long-term opioid use: increasing opioid daily doses, prescription period ≥7 days and long-acting opioids initiated by non-EDs.
CONCLUSIONS: The majority of opioid-naïve patients in tertiary hospital settings in Malaysia were prescribed opioids for short-term use. The progression to long-term use among opioid-naïve patients was attributed to the prescription of higher opioid doses for a longer duration as well as long-acting opioids initiated by non-ED hospital departments.
SETTING: Hospital surgical ward.
SUBJECTS: Women (107 Indian, 184 Malay, and 750 Han Chinese) undergoing total hysterectomy surgery.
METHODS: Morphine consumption, preoperative pain, and postoperative pain were evaluated in relation to genetic variability comprising 19 single-nucleotide polymorphisms (SNPs) in 14 genes involved in glial activation, inflammatory signaling, and neuronal regulation, plus OPRM1 (1 SNP) and COMT (3 SNPs).
RESULTS: Pre- and postoperative pain and age were associated with increased and decreased morphine consumption, respectively. In Chinese patients, only 8% of the variability in consumption could be explained by these nongenetic and genetic (BDNF, IL1B, IL6R, CRP, OPRM1, COMT, MYD88) factors. However, in Indian patients, 41% of morphine consumption variability could be explained by age (explaining <3%) and variants in OPRM1 rs1799971, CRP rs2794521, TLR4 rs4986790, IL2 rs2069762, COMT rs4818, TGFB1 rs1800469, and IL6R rs8192284 without controlling for postoperative pain.
CONCLUSIONS: This is the highest known value reported for genetic contributions (38%) to morphine use in the acute postoperative pain setting. Our findings highlight the need to incorporate both genetic and nongenetic factors and consider ethnicity-dependent and nonadditive genotypic models in the assessment of factors that contribute to variability in opioid use.
AIM: To assess plasma testosterone and sexual function in Southeast Asian men on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT).
METHODS: 76 sexually active men on MMT (mean age = 43.30 ± 10.32 years) and 31 men on BMT (mean age = 41.87 ± 9.76 years) from a Southeast Asian community were evaluated using plasma total testosterone (TT) and prolactin levels, body mass index, social demographics, substance use measures, and depression severity scale.
OUTCOMES: Prevalence and associated factors of TT level lower than the reference range in men on MMT or BMT.
RESULTS: More than 1 third of men (40.8%, n = 31) on MMT had TT levels lower than the reference range, whereas 1 fourth of men (22.6%, n = 7) on BMT did. At univariate analysis, MMT vs BMT (β = 0.298, adjusted R2 = 0.08, P = .02) and body mass index (β = -0.23, adjusted R2 = 0.12, P = .02) were associated with changes in TT after stepwise regression. There were no significant associations with age; Opiate Treatment Index Q scores for alcohol, heroin, stimulant, tobacco, or cannabis use and social functioning domain; education levels; hepatitis C status; and severity of depression. Prolactin level did not differ between the MMT and BMT groups.
CLINICAL IMPLICATIONS: The sex hormonal assay should be used regularly to check men on MMT.
STRENGTHS AND LIMITATIONS: This is the first study conducted in the Southeast Asian community. Our study was limited by the lack of a healthy group as the reference for serum levels of testosterone and prolactin.
CONCLUSIONS: The findings showed that plasma testosterone levels are lower in MMT than in BMT users. Hence, men who are receiving MMT should be screened for hypogonadism routinely in the clinical setting. Yee A, Loh HS, Danaee M, et al. Plasma Testosterone and Sexual Function in Southeast Asian Men Receiving Methadone and Buprenorphine Maintenance Treatment. J Sex Med 2018;15:159-166.
DESIGN, SETTING AND PARTICIPANTS: Ten-year horizon (2016-25) modeling study of opioid addiction epidemic and treatment that accommodated potential peer effects in opioid use initiation and supply-induced treatment demand in three Ukrainian cities: Kyiv, Mykolaiv and Lviv, comprising a simulated population of people at risk of and with OUD.
MEASUREMENTS: Incremental cost per quality-adjusted life-year gained in the simulated population.
FINDINGS: An estimated 12.2-, 2.4- and 13.4-fold OAT capacity increase over 2016 baseline capacity in Kyiv, Mykolaiv and Lviv, respectively, would be cost-effective at a willingness-to-pay of one per-capita gross domestic product (GDP) per quality-adjusted life-year gained. This result is robust to parametric and structural uncertainty. Even under the most ambitious capacity increase, OAT coverage (i.e. the proportion of people with OUD receiving OAT) over a 10-year modeling horizon would be 20, 11 and 17% in Kyiv, Mykolaiv and Lviv, respectively, owing to limited demand.
CONCLUSIONS: It is estimated that a substantial increase in opioid agonist treatment (OAT) capacity in three Ukrainian cities would be cost-effective for a wide range of willingness-to-pay thresholds. Even a very ambitious capacity increase, however, is unlikely to reach internationally recommended coverage levels. Further increases in coverage may be limited by demand and would require addressing existing structural barriers to OAT access.