The test-retest reliability of the Opiate Treatment Index in nyaope users in Johannesburg.

Background: Epidemiological studies suggest that nyaope, a heroin-based drug, is widely used in South Africa. Yet few reliable research tools are available to assess treatment outcomes of users. The Opiate Treatment Index (OTI), a tool developed in Australia, could potentially facilitate research on context-specific South African treatment outcomes. However, we know little of its test-retest reliability. Aim: This study aimed to assess the test-retest reliability of the OTI among a sample of nyaope users in Johannesburg. Setting: This study was conducted across three substance use treatment facilities in Johannesburg. Methods: The OTI was administered to 53 nyaope users at baseline and one week later. To determine the test-retest reliability of the OTI, the intra-class correlation coefficients (ICC) and the Brennan-Prediger coefficients of the two interviews were calculated. Results: The ICC of the Q-scores from the data sets along with the Brennan-Prediger coefficient for the substance use domain were calculated. The ICC for nyaope was 0.38. Brennan-Prediger coefficients were as follows: alcohol - 0.96, crack-cocaine - 0.89, cannabis - 0.92, methaqualone - 0.85 and crystal methamphetamine - 0.89. Conclusion: A significant positive finding was the excellent test-retest reliability of the injecting and sexual behaviour domains and moderate reliability of the criminality, general health and social functioning domains. Contribution: The results of this study provide insight into the reliability of this tool and for its use in future studies in the South African context.

The incidence of new mental health disorders after acute pancreatitis: A large, propensity-matched, observational study.

INTRODUCTION: The prevalence of acute pancreatitis (AP) and mental health disorders (MHDs) are rising. While the association between chronic pancreatitis (CP) and MHDs is established, it is unknown whether there is a risk of MHDs after an index episode of AP. The aim of this study was to evaluate the incidence of MHDs and pharmacotherapy use after an episode of AP. METHODS: This was a large observational study using the TriNetX research network, an electronic health record dataset containing inpatient and outpatient data from more than 50 healthcare organizations. Patients with AP from 2015-2020 were identified. Four cohorts were created: acute necrotizing pancreatitis (ANP), acute pancreatitis without necrosis (AP-WON), acute appendicitis, and healthy controls without pancreatitis. The cohorts were matched by age, sex, race, ethnicity, and nicotine and alcohol use. The primary outcome was new composite MHDs at one-year. Secondary outcomes included stratified MHDs, psychiatric medication use, opioid analgesic use, and all-cause mortality. RESULTS: The ANP, AP-WON, appendicitis, and healthy control cohorts contained 11,806, 177,266, 27,187, and 561,833 patients, respectively. Patients with AP-WON had significantly higher rates of composite MHDs compared with those hospitalized for appendicitis (9.7% vs 4.7%, HR 1.9, 95% CI 1.7-1.9). This association was augmented when comparing ANP to appendicitis (12.8% vs 5.2%, HR 2.4, 95% CI 2.1-2.7). All secondary outcomes were observed at significantly higher rates in the AP-WON cohort when compared to appendicitis. Again, these associations were augmented comparing ANP to appendicitis. CONCLUSION: Compared with controls, patients with AP had significantly higher rates of new MHDs and their associated pharmacotherapies at one-year, suggesting that a single episode of AP may independently place patients at risk for developing MHDs irrespective of whether they go on to develop CP.

Effect of single-shot intrathecal morphine versus continuous epidural analgesia on length of stay after gastrectomy for cancer: a retrospective cohort study.

BACKGROUND: Single-dose intrathecal opiates (ITO) could shorten the length of hospital stay compared to thoracic epidural analgesia (TEA). This study aimed to compare TEA with TIO in terms of length of hospital stay, pain control, and parenteral opioid consumption in patients undergoing gastrectomy for cancer. METHODS: The patients who underwent gastrectomy for cancer in 2007-2018 at the CHU de Québec-Université Laval were included. The patients were grouped as TEA and intrathecal morphine (ITM). The primary outcome was the length of hospital of stay (LOS). The secondary outcomes were numeric rating scales (NRS) for pain and parenteral opioid consumption. RESULTS: A total of 79 patients were included. There were no differences in preoperative characteristics between the two groups (all P > 0.05). The median LOS was shorter in the ITM group than in the TEA group (median, 7.5 vs. 10 days, P = 0.049). The opioids consumption at 12, 24, and 48 h postoperatively was significantly lower in the TEA group at all time points. The NRS score for pain was lower in the TEA group than in the ITM group at all time points (all P < 0.05). CONCLUSIONS: Patients with ITM analgesia undergoing gastrectomy presented shorter LOS than those with TEA. ITM had an inferior pain control that did not have a clinical impact on recovery in the cohort studied. Given the limitations of this retrospective study, further trials are warranted.

Eating disorders and substance use: Examining associations among US college students.

OBJECTIVE: To investigate associations between reported eating disorder (ED) diagnosis and substance use disorder (SUD) diagnosis, substance misuse, and illicit drug use among US college students. METHOD: Data consisting of n = 414,299 students' responses to the National College Health Assessment survey conducted by the American College Health Association between fall 2015 and spring 2019 were utilized for this study. Unadjusted and adjusted odds ratios were used to determine the association of reported ED diagnosis with reported SUD diagnosis, misuse of cigarettes, e-cigarettes, alcohol, marijuana, cocaine/methamphetamine, sedatives, hallucinogens, opiates, inhalants, MDMA, and other club drugs, as well as illicit use of prescription pain killers, prescription sedatives, and prescription stimulants. A sensitivity analysis investigating associations between reported anorexia nervosa (AN), bulimia nervosa (BN), and each substance use outcome was also conducted. RESULTS: Among all in our analytic cohort, 7.15% reported receiving an ED diagnosis or being treated for an ED in the last 12 months. Students with ED indications were significantly more likely to report each of the substance use outcomes investigated in this study, including SUD diagnosis (aOR: 7.43; 95% CI: 6.98, 7.92; p < .0001), opiate misuse (aOR: 8.35; 95% CI: 7.38, 9.45; p < .0001), and misuse of other club drugs (aOR: 10.37; 95% CI: 9.10, 11.81; p < .0001) than peers without reported EDs. Both AN and BN were associated with an increased likelihood of SUD diagnosis. DISCUSSION: These findings demonstrate strong associations between EDs and the most extensive list of substance use outcomes explored in the context of college setting ED research to date.

A national population-based study of cannabis use and correlates among U.S. veterans prescribed opioids in primary care.

BACKGROUND: Cannabis is marketed as a treatment for pain. There is limited data on the prevalence of cannabis use and its correlates among Veterans prescribed opioids. OBJECTIVE: To examine the prevalence and correlates of cannabis use among Veterans prescribed opioids. DESIGN: Cross-sectional study. PARTICIPANTS: Veterans with a urine drug test (UDT) from Primary Care 2014-2018, in 50 states, Washington, D.C., and Puerto Rico. A total of 1,182,779 patients were identified with an opioid prescription within 90 days prior to UDT. MAIN MEASURES: Annual prevalence of cannabis positive UDT by state. We used multivariable logistic regression to assess associations of demographic factors, mental health conditions, substance use disorders, and pain diagnoses with cannabis positive UDT. RESULTS: Annual prevalence of cannabis positive UDT ranged from 8.5% to 9.7% during the study period, and in 2018 was 18.15% in Washington, D.C. and 10 states with legalized medical and recreational cannabis, 6.1% in Puerto Rico and 25 states with legalized medical cannabis, and 4.5% in non-legal states. Younger age, male sex, being unmarried, and marginal housing were associated with use (p < 0.001). Post-traumatic stress disorder (adjusted odds ratio [AOR] 1.17; 95% confidence interval [CI] 1.13-1.22, p < 0.001), opioid use disorder (AOR 1.14; CI 1.07-1.22, p < 0.001), alcohol use disorder or positive AUDIT-C (AOR 1.34; 95% CI 1.28-1.39, p < 0.001), smoking (AOR 2.58; 95% CI 2.49-2.66, p < 0.001), and other drug use disorders (AOR 1.15; 95% CI 1.03-1.29, p = 0.02) were associated with cannabis use. Positive UDT for amphetamines AOR 1.41; 95% CI 1.26-1.58, p < 0.001), benzodiazepines (AOR 1.41; 95% CI 1.31-1.51, p < 0.001) and cocaine (AOR 2.04; 95% CI 1.75-2.36, p < 0.001) were associated with cannabis positive UDT. CONCLUSIONS: Cannabis use among Veterans prescribed opioids varied by state and by legalization status. Veterans with PTSD and substance use disorders were more likely to have cannabis positive UDT. Opioid-prescribed Veterans using cannabis may benefit from screening for these conditions, referral to treatment, and attention to opioid safety.

Constipation After Elective Laparoscopy for Benign Gynecological Indications-A Prospective Observational Study.

STUDY OBJECTIVE: Discover the rate of post-operative constipation in participants undergoing elective laparoscopy for benign gynecological indications DESIGN: Prospective observational study SETTING: Single site, tertiary level gynecology unit with a focus on pelvic pain and endometriosis. PATIENTS: Recruited participants were patients of the institution over the age of 18 who had planned to undergo an elective laparoscopy for benign gynecological indications prior to enrolment in the study. Participants were excluded if they were not English speaking, had a chronic bowel condition (with the exception of irritable bowel syndrome), were planned to have bowel surgery, hysterectomy, or converted to laparotomy. INTERVENTION: In this prospective study, participants completed 3 consecutive surveys. One prior to surgery, one a week post-surgery, and a third 3 months post-surgery. The surveys collected data regarding the participant's bowel habits, pain relief used, laxatives used, and the distress or bother caused by their bowels. MEASUREMENT AND MAIN RESULTS: Constipation was defined by a modified ROME IV criteria. Opiate use and laxative use were defined by patient-reported tablet counts. The level of distress was measured as a continuously variable scale from 0 to 100. Variables adjusted for included subject's demographics, pre-operative constipation, indication for surgery, duration of surgery, estimated blood loss, opiate use (preoperative, peri-operative, and post-operative), laxative use, and length of stay. A total of 153 participants were recruited, of which 103 completed both the pre-operative and post-operative survey. Post-operative constipation was present in 70% of participants. The mean length of time to first bowel motion was 3 days, with 32% of participants having their first bowel motion after the third post-operative day. The level of bother caused by their bowel habit was higher in the constipation group compared to those without constipation. Post-operatively opiates were used in 84.9% of participants, and laxatives were used in 47.1%. Visits to the general practitioner for constipation occurred in 5.8% of participants. CONCLUSION: Post-operative constipation is common and bothersome in participants who undergo elective laparoscopy for benign gynecological indications. Analysis of individual variables failed to identify any factors that influenced the rate of constipation.

Development of an intervention to manage benzodiazepine dependence and high-risk use in the context of escalating drug related deaths in Scotland: an application of the MRC framework.

BACKGROUND: Scotland has the highest rate of drug related deaths (DRD) in Europe. These are deaths in people who use drugs such as heroin, cocaine, benzodiazepines and gabapentinoids. It is a feature of deaths in Scotland that people use combinations of drugs which increases the chance of a DRD. Many deaths involve 'street' benzodiazepines, especially a drug called etizolam. Many of the 'street' benzodiazepines are not licensed in the UK so come from illegal sources. People who use opiates can be prescribed a safer replacement medication (e.g., methadone). While guidance on management of benzodiazepines use highlights that there is little evidence to support replacement prescribing, practice and evidence are emerging. AIM: To develop an intervention to address 'street' benzodiazepines use in people who also use opiates. METHODS: The MRC Framework for Complex Interventions was used to inform research design. Co-production of the intervention was achieved through three online workshops with clinicians, academics working in the area of substance use, and people with lived experience (PWLE). Each workshop was followed by a PWLE group meeting. Outputs from workshops were discussed and refined by the PWLE group and then further explored at the next workshop. RESULTS: After these six sessions, a finalised logic model for the intervention was successfully achieved that was acceptable to clinicians and PWLE. Key components of the intervention were: prescribing of diazepam; anxiety management, sleep, and pain; and harm reduction resources (locked box and a range of tips), personal safety conversations, as well as a virtual learning environment. CONCLUSION: A co-produced intervention was developed for next stage clinical feasibility testing.

A comparison of risk factors for relapse in opiate-related and stimulant-related substance use disorders: A cross-sectional multicenter study.

INTRODUCTION: Recognizing the specific factors in relapse disorders related to each substance can help improve treatment methods and adopt more effective preventive strategies. This study aimed to compare the situational factors associated with relapse in opiate-related disorders with stimulant-related disorders (SRDs) of those referred to substance misuse treatment centers. DESIGN: This study was a cross-section type. METHODS: The study participants were 150 clients with SRDs and 150 with opiate-related disorders. Samples were selected using two stages random sampling method. Data were collected through a demographic questionnaire and the Inventory of Drug-Taking Situations (IDTS). RESULTS: The mean score of IDTS in the two groups was significantly different (X̄1  = 45.93 ± 11.12 vs. X̄2  = 48.34 ± 15.07; t = 3.32, p < 0.01). The mean scores of 'unpleasant emotions,' 'physical discomfort,' 'conflict with others,' and 'social pressure to use and urge/temptations' subscales were significantly higher in the stimulant group than in the opiate group (p < 0.05). However, the mean of the testing' personal control' subscale was higher in the opiate group than in the stimulant group (p < 0.05). CONCLUSION: This study reveals that despite some similarities, relapse-related situational factors in opiates and stimulants differ. Some situational factors, such as social pressure and coping with unpleasant emotions, play a more critical role in relapse to both stimulant and opiate groups.

Preemptive multimodal analgesia and post-operative pain outcomes in total hip and total knee arthroplasty.

BACKGROUND: Use of multimodal analgesia (MMA) prior to orthopedic surgery has been adopted by many practitioners as a strategy to minimize use of opioid medications. The purpose of this investigation was to quantify the effect of a preemptive three-drug regimen (acetaminophen, celecoxib, and gabapentin) in terms of post-operative opioid consumption and pain control in the field of total joint arthroplasty. METHODS: A retrospective chart review was conducted on 1691 patients who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA) and stratified by whether they received a preemptive three medication analgesic therapy (acetaminophen, celecoxib, and gabapentin) within 30 to 60 min prior to entering the operating room. Post-operative opioid consumption as well as subjectively reported patient pain scores were assessed throughout their hospital stay. RESULTS: A total of 1416 eligible patients were identified with 485 undergoing THA and 931 undergoing TKA. Statistically significant reductions in oral morphine equivalents were shown on post-operative day zero and two within the TKA cohort, and non-significant reductions were demonstrated in other intervals for both procedure types. Statistically significant reductions in patient reported pain scores were shown in nearly every time interval in both procedure types. CONCLUSION: The receipt of preemptive acetaminophen, celecoxib, and gabapentin 30-60 min prior to total joint arthroplasty demonstrated modest reductions in opioid requirements post-operatively. Patients receiving preemptive MMA reported lower pain scores throughout nearly every time interval during their admission after surgery. Further investigations are warranted regarding optimal preoperative medication therapies to promote adequate post-operative pain control-and ultimately diminished opioid consumption-in the setting of total joint arthroplasty.

Biogenesis, physiological functions and potential applications of extracellular vesicles in substance use disorders.

Substance use disorder (SUD) is a growing health problem that affects several millions of people worldwide, resulting in negative socioeconomic impacts and increased health care costs. Emerging evidence suggests that extracellular vesicles (EVs) play a crucial role in SUD pathogenesis. EVs, including exosomes and microvesicles, are membrane-encapsulated particles that are released into the extracellular space by most types of cells. EVs are important players in mediating cell-to-cell communication through transfer of cargo such as proteins, lipids and nucleic acids. The EV cargo can alter the status of recipient cells, thereby contributing to both physiological and pathological processes; some of these play critical roles in SUD. Although the functions of EVs under several pathological conditions have been extensively reviewed, EV functions and potential applications in SUD remain less studied. In this review, we provide an overview of the current knowledge of the role of EVs in SUD, including alcohol, cocaine, heroin, marijuana, nicotine and opiate abuse. The review will focus on the biogenesis and cargo composition of EVs as well as the potential use of EVs as biomarkers of SUD or therapeutic targets in SUD.

Fos-expressing neuronal ensembles in rat infralimbic cortex encode initial and maintained oxycodone seeking in rats.

Neuronal ensembles within the infralimbic cortex (IL) and their projections to the nucleus accumbens (NAc) mediate opiate seeking in well-trained rats. However, it is unclear how early this circuitry is recruited during oxycodone self-administration. Here, we used retrograde labelling (CTb) and immunohistochemistry to identify NAc-projecting neurons in the IL that were activated during initial oxycodone seeking. Next, we sought to determine the role of IL neuronal ensembles in initial oxycodone self-administration. We used the Daun02 procedure in male and female Fos-LacZ rats to chemogenetically inactivate IL Fos-expressing neurons at different time points in oxycodone self-administration training: immediately after meeting criteria for acquisition of behaviour and following nine daily sessions with increasing schedules of reinforcement (FR1, FR2 and FR3) in which rats demonstrated stable oxycodone intake under increasing effort to self-administer. We found that Daun02 infusions attenuated oxycodone seeking at both the initial learning and well-trained time points. These results suggest that IL neuronal ensembles are formed during initial learning of oxycodone self-administration and required for the maintenance and expression of oxycodone seeking.

Combined effects of quetiapine and opioids: A study of autopsy cases, drug users and sedation in rats.

Fatal opioid poisonings often involve methadone or morphine. This study aimed to elucidate if quetiapine, a widely used sedative antipsychotic medication, may increase the risk of fatal opioid poisoning by additive inhibitory effects on the central nervous system. We used data from 323 cases of fatal methadone or/and morphine poisonings autopsied from 2013 to 2020, a survey of 34 drug users, and performed blinded placebo-controlled studies in 75 Flinders Resistant Line rats receiving three cumulative intraperitoneal doses of vehicle, methadone (2.5, 10 and 15 mg/kg), morphine (3.75, 15 and 22.5 mg/kg), quetiapine (3, 10 and 30 mg/kg) or quetiapine combined with methadone or morphine. Quetiapine was detected in 20.4% of fatal opioid poisonings with a significantly increased frequency over time, primarily in low or therapeutic concentrations, and was not associated with methadone or morphine concentrations. Use of quetiapine, most commonly in low-to-moderate doses to obtain a sleep-inducing or tranquillizing effect, was reported by 67.6% of survey respondents. In the animal studies, a significant impairment of sedation score, performance on the rotarod and open field mobility was observed in all treatment groups compared with vehicle. However, the effect of quetiapine plus the opioid was not significantly different from that of the opioid alone. Thus, no additive sedative effects were observed in rats. Our results suggest that quetiapine is more often an innocent bystander than a contributor to fatal opioid poisoning. However, the combined effects on other parameters, including blood pressure, cardiac rhythm and respiratory rate, need investigation.

A Theoretical Endogenous Opioid Neurobiological Framework for Co-occurring Pain, Trauma, and Non-suicidal Self-injury.

PURPOSE OF REVIEW: Individuals with chronic pain are significantly more likely to have experienced overwhelming trauma early and often in key developmental years. There is increasing acknowledgment that childhood trauma disrupts how individuals process and cope with both physical and emotional pain. Emerging studies acknowledge elevated rates of non-suicidal self-injury (NSSI) in chronic pain populations. This review provides a theoretical framework to understand the relationship between NSSI behavior and pain experience in persons with chronic pain and childhood trauma histories. We discuss how NSSI may act to regulate neurobiological (e.g., endogenous opioid systems) and psychological (e.g., heightened negative affect and emotion dysregulation) systems affected by childhood trauma, leading to temporary pain relief and a cycle of negative reinforcement perpetuating NSSI. As these concepts are greatly understudied in pain populations, this review focuses on key areas relevant to chronic pain that may provide a testable, conceptual framework to support hypothesis generation, future empirical investigation, and intervention efforts. RECENT FINDINGS: See Fig. 1. See Fig. 1.

Take-Home Naloxone Kits: Attitudes and Likelihood-Of-Use Outcomes from a European Survey of Potential Overdose Witnesses.

BACKGROUND: Injectable naloxone is already provided as take-home naloxone (THN), and new concentrated intranasal naloxone is now being introduced in Europe. Despite evidence of the effectiveness and cost-effectiveness of THN, little is known about the attitudes of key target populations: people who use opioids (PWUO), family/friends, and staff. We examined the acceptability of different naloxone devices (ampoule, prefilled syringe, and concentrated nasal spray) across 5 European countries. OBJECTIVES: The aim of this study was to compare THN target groups (PWUO vs. family/friends vs. staff) in their past rates of witnessed overdose and THN administration (as indicators of future use), current THN device preference, and THN carriage on the day of survey. METHOD: Cross-sectional survey of respondents (age ≥18) in addiction treatment, harm reduction, and recovery services in Denmark, England, Estonia, Norway, and Scotland. A purpose-developed questionnaire (59 items) was administered in the local language electronically or in a pen-and-paper format. RESULTS: Among n = 725 participants, 458 were PWUO (63.2%), 214 staff (29.5%), and 53 (7.3%) family members. The groups differed significantly in their likelihood-of-future THN use (p < 0.001): PWUO had the highest rate of previously witnessing overdoses (352; 77.7%), and staff members reported the highest past naloxone use (62; 30.1%). Across all groups, most respondents (503; 72.4%) perceived the nasal spray device to be the easiest to use. Most reported willingness to use the spray in an overdose emergency (508; 73.5%), followed by the prefilled syringe (457; 66.2%) and ampoules (64; 38.2%). Average THN carriage was 18.6%, ranging from 17.4% (PWUO) to 29.6% (family members). CONCLUSION: Respondents considered the concentrated naloxone nasal spray the easiest device to use. Still, most expressed willingness to use the nasal spray as well as the prefilled syringe in an overdose emergency. Carriage rates were generally low, with fewer than 1 in 5 respondents carrying their THN kit on the day of the survey.

Historical Trends in Veteran Community Substance Use Treatment: 2000-2019.

Background: Substance use is a significant health crisis for the Veteran population. Prior research has thoroughly examined Veteran substance use within Veterans Health Administration (VHA) settings. However, such data tends to be outdated, and there is minimal research on substance use services delivered outside of VHA systems. This study examines historical patterns of Veteran substance use using a large sample of community-based substance-use treatment admissions. Methods: Data were drawn from the Substance Abuse and Mental Health Data Archive Treatment Episode Data Set-Admissions. Of the 39,425,886 total admissions between 2000 and 2019, 1,361,339 were of Veterans. Analyses compared Veteran versus non-Veteran admissions on demographics and historical trends in nature of substance-use admissions. Results: Relative to non-Veterans, Veteran admissions were more likely to be prompted by alcohol use. Over time, heterogeneity in substances prompting admissions has increased dramatically for both Veterans and non-Veterans, with particularly notable increases in opiate and stimulant use. Conclusion: Results suggest Veterans admitted to community substance-use treatment are unique relative to their non-Veteran peers. Development and implementation of treatments to target a range of substances while also considering the environmental challenges (e.g., homelessness) commonly faced by this population appear essential to best servicing community-based Veterans.

Implementation of enhanced recovery protocols reduces opioid use in pediatric laparoscopic cholecystectomy surgery.

PURPOSE: Enhanced recovery protocols [ERPs] standardize care and have been demonstrated to improve surgical quality in adults. We retrospectively compared outcomes before and after implementation of ERPs in children undergoing elective laparoscopic cholecystectomy [ELC] surgery. METHODS: A pediatric-specific ERP was implemented for children undergoing ELC at one [C1] of the two Pediatric Surgical Centers in July 2016. We retrospectively reviewed 606 patients undergoing ELC between July 2014 and December 2019. Of these, 206 patients underwent ELC prior to ERP implementation [Pre-ERP] were compared to 400 patients undergoing ELC managed in the post-ERP implementation period (between January 2017 and December 2019), 21 of which were managed by enhanced recovery protocol. Primary Outcomes included immediate peri-operative and post-operative narcotic use in mean morphine equivalents [MME], narcotics at discharge, complications, nurse calls and returns to system [RTS]. RESULTS: There was a significant decrease in opioid use both post-operatively and at time of discharge in the ERP managed cohort. The MME use during the post-operative period was 0.85 in the in ERP-compliant patients compared to 6.40 in the non-compliant group (p < 0.027). Eighty-six percent of ERP-compliant patients in the study required no narcotics at discharge, which was statistically significant when compared to ERP non-compliant cohort (p < 0.0001). There was also no change in RTS, nurse calls or complications. In addition, in the post-ERP period (2017-2019), a dominant proportion of patients at C1 partially complied with the ERP, resulting in a statistically significantly decrease of opioid use between sites in the post-op period (6.54 vs 10.57 MME) post-ERP (p < 0.001). Similar effects were noted in discharge narcotics. CONCLUSION: The use of pediatric-specific ERP in children undergoing ELC is safe, effective, and provides compassionate pain control while leading to a reduction in opioid use peri-operatively and at discharge. This improvement occurred without changes in RTS, nursing calls or complications. LEVEL OF EVIDENCE: Level III; Retrospective study.

Stability of Cocaine, Opiates, and Metabolites in Dried Saliva Spots.

Drug abuse still represents a global problem, and it is associated with an increased risk of diseases, injuries, and deaths. Cocaine (COC) and opiates are the most abused drugs and account for a significant number of fatalities. Therefore, it is important to develop methods capable of effectively identifying and quantifying these substances. The present study aims to evaluate the long-term stability of COC, ecgonine methylester (EME), benzoylecgonine (BEG), cocaethylene (COET), norcocaine (NCOC), morphine (MOR), codeine (COD) and 6-monoacetylmorphine (6-MAM) in oral fluid samples. The analytes of interest were isolated from the matrix (50 µL) using the dried saliva spots (DSS) sampling approach and were subsequently analyzed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The parameters that could influence the stability of the target compounds were studied, and these were storage temperature, light, use of preservatives (and respective concentrations), and time. The effects of each parameter were evaluated using the design of experiments (DOE) approach. The stability of the target analytes was improved when the DSS were stored at room temperature, in the presence of light and using 1% sodium fluoride. The best conditions were then adopted for the DSS storage and long-term stability was assessed. COD was only stable for 1 day, EME was stable for 3 days, COC, COET, NCOC and 6-MAM were stable for 7 days, MOR for 14 days and BEG remained stable throughout the study (136 days). This is the first study that evaluates the stability of these compounds in oral fluid samples after application in DSS cards, and optimizes the conditions in order to improve their stability.

Gabapentin Premedication to Reduce Postoperative Pain for Pediatric Tonsillectomy/Adenoidectomy: A Pilot Study.

PURPOSE: To examine the effects of preoperative gabapentin administration on postoperative pain in pediatric patients undergoing tonsillectomy/adenoidectomy (T/A) in a single ambulatory surgery location within a pediatric healthcare organization. DESIGN: This randomized, controlled pilot study enrolled patients age 3-18 years with American Society of Anesthesiologists (ASA) scores of I-II undergoing T/A. METHODS: Both gabapentin and placebo groups were given study medication preoperatively and received standard opiate regimens intraoperatively and postoperative pain instructions. Outcome measurements included: time to first analgesic medication in the postanesthesia care unit (PACU), mean acetaminophen, ibuprofen, and opiate doses in mg/kg. Additionally, we examined pain scores, medication use, and side effects reported by daily pain diaries completed by patients/families for 3 days postoperatively. FINDINGS: Forty-nine patients were included in final analysis (gabapentin n = 26, placebo n = 23). Demographic and clinical characteristics of both groups were similar; the majority (46 of 49) were under the age of 13. Both groups received opiates in PACU. Some patients in both groups received hydrocodone/acetaminophen postoperatively. There were no reported differences in side effects between groups. Gabapentin group reported less use of opiates, acetaminophen, and ibuprofen post-discharge. We identified small effect sizes for opiates and acetaminophen, and medium effect size for ibuprofen (80.1% gabapentin versus 100% placebo, RR 0.81 [95% CI 0.67-0.97]). Median pain scores were 4 on a scale of 10 for both groups for all 3 days of follow-up. Overall median satisfaction score was 9, with a mean difference of 0.35 (95% CI -0.78 - 1.37). Analysis of variance revealed no difference in pain scores or satisfaction per pain diaries between the groups in general and no difference in score trajectory. CONCLUSIONS: We were able to establish a rigorous process and feasibility to launch a larger, multi-center trial to examine this important issue. There remain few evidence-based options for acute pain relief in pediatric surgical populations besides opiates. Identifying opiate alternatives that are effective, cost efficient and safe are needed for pediatric tonsillectomy patients.

Expeditious Access to Morphinans by Chemical Synthesis.

Morphinans are essential medicines derived entirely from poppy supply chains rendered increasingly volatile by climate change. Here, we report a seven-step, asymmetric chemical synthesis of (-)-codeine from simple materials that requires a total combined reaction time of fewer than 24 hours. The efficiency of our approach arises from a double-Heck cyclization reaction that generates two rings and two contiguous stereogenic carbon centres in the one pot. A subsequent photo-redox hydroamination protocol provides a novel, atom-economical means for assembling the piperidine D-ring of codeine. Simple modifications to the closing stages of our sequence offer effective access to pharmacologically valuable derivatives of N-demethyl codeine. Our work highlights the capacity for contemporary, stand-alone chemical synthesis regimes to diversify access to essential opiate medicines.

Opioid Use Among Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Despite reported adverse effects of opioids in patients with inflammatory bowel disease (IBD), the burden of opioid use in this population appears to be high. We performed a systematic review and meta-analysis of prior studies to determine the prevalence of opioid use among patients with IBD as well as risk factors and outcomes associated with opioid use in this population. METHODS: We conducted a systematic search of MEDLINE, Embase, Web of Science, and the Cochrane Library through November of 2019. Primary outcomes included the prevalence of opioid use and demographic and clinical variables associated with opioid use in patients with IBD. Quality was assessed using the Newcastle-Ottawa scale. We used random-effect meta-analysis to estimate pooled relative risks (RRs) and 95% CIs. RESULTS: Of 780 citations identified, 31 were included in our study. The prevalence of opioid use was 21% (95% CI, 13%-30%) in the outpatient setting. Likewise, 62% (95% CI, 25%-92%) of patients received opioids while hospitalized for IBD. Opioid use was associated with female sex (RR 1.20; 95% CI 1.03-1.40), depression (1.99; 95% CI 1.80-2.19), substance abuse (4.67; 95% CI 2.87-7.60), prior gastrointestinal surgery (2.33; 95% CI 1.66-3.26), biologic use (1.36; 95% CI 1.06-1.74), and steroid use (1.41; 95% CI 1.04-1.91). Based on the systematic review, opioid use also appeared to be associated with increased IBD activity, healthcare use, infection, and mortality. CONCLUSION: In a systematic review and meta-analysis, we found that 21% of outpatients with IBD (and 62% of hospitalized patients) are opioid users; use is associated with more severe IBD and increased healthcare use. Further studies are required to determine whether opioids are the cause or an effect of these associations. Nonetheless, urgent interventions are needed to reduce opioid use, improve disease-related outcomes and reduce healthcare costs.