METHODS: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models.
RESULTS: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95.
CONCLUSIONS: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade.
OBJECTIVE: The objective of this study was to compare the clinical efficacy of s.c. tramadol vs. i.v. tramadol in patients with moderate pain due to extremity injury in the ED.
DESIGN, SETTINGS, AND PARTICIPANTS: This non-inferiority randomized controlled trial included adult patients presented to an academic, tertiary hospital ED with moderate pain (pain score of 4-6 on the visual analog scale) due to extremity injury. Intervention patients stratified to pain score were randomized to receive 50 mg of i.v. or s.c. tramadol.
OUTCOMES MEASURE AND ANALYSIS: Primary outcome measure was the difference in the pain score reduction at 30 min after tramadol administration between the two groups. The noninferiority null hypothesis was that the therapeutic difference in terms of pain score reduction of more than 0.8 exists between the two treatment groups at the endpoint.
MAIN RESULTS: In total 232 patients were randomized to i.v. ( n = 115) or s.c. ( n = 117). Although 225 were analyzed in the per-protocol population (i.v. = 113; s.c. = 112). The baseline median pain score was 6 (IQR, 5-6). Median pain score reduction at 30 min after administration was 2 (IQR, 1-3) in the IV group vs. 2 (IQR, 1-2) in the s.c. group with a median difference of 0 (IQR, 0-0), which was below the prespecified noninferiority margin of 0.8. Adverse events in the i.v. group were higher compared to the s.c. group (33.6% vs. 8.9%, P ≤ 0.001).
CONCLUSIONS: The s.c. tramadol is noninferior to i.v. tramadol in the treatment of moderate pain from extremity injuries.
METHODS: Sociometric data on networks on people who inject drugs from Hartford, CT, which were collected in 2012-2013, provided assessment of risk behaviors among 1574 injection network members, including participation in OAT and SSP. Subject's network characteristics were examined in relation to retention in OAT, as well as secondary syringe exchange using exponential random graph model (ERGM) and regression.
RESULTS: Based on the analysis, we found that probability of individuals being retained in OAT was positively associated with the OAT retention status of their peers within the network. Using simulations, we found that higher levels of positive correlation of OAT retention among network members can result in reduced risk of transmission of HIV to network partners on OAT. In addition, we found that secondary syringe exchange engagement was associated with higher probability of sharing of paraphernalia and unsterile needles at the network level.
CONCLUSIONS: Understanding how networks mediate risk behaviors is crucial for making progress toward ending the HIV epidemic.
STUDY DESIGN: A cross-sectional study, conducted across Punjab, Pakistan.
METHOD: The study deployed a validated survey to evaluate the competencies and practices of the community and hospital pharmacists.
RESULTS: 504 community pharmacists and 279 hospital pharmacists participated in the survey with an overall response rate of 85.5%. Almost half of the respondents 'never' or 'sometimes' made clinical notes in a journal or dispensing software to monitor ongoing opioid use. Generally, pharmacists were reluctant to collaborate with physicians or notify police regarding the abuse/misuse of opioids. Hospital pharmacists achieved significantly higher mean competency scores than chain and independent community pharmacists (p<0.05). In competency evaluation, three priority areas emerged that require additional training, that is, 'opioid overdose management', 'opioid use monitoring' and 'therapeutic uses of opioids'.
CONCLUSION: Both community and hospital pharmacists hold significant positions and potential to contribute meaningfully to the mitigation of harms and risks associated with opioids. Nevertheless, this study underscores notable deficiencies in the competence of pharmacists, whether in hospital or community settings in Punjab, concerning various aspects related to the dispensing and utilisation of opioids. It also highlights the pressing need for the development of strategies aimed at improving several practice areas including the documentation, the quality of patient counselling, the effectiveness of reporting mechanisms for opioid abuse and the stringent enforcement of regulatory policies to curtail opioid misuse. Thus, to mitigate the opioid epidemic in Pakistan, it is imperative to institute opioid stewardship initiatives aimed at rectifying the competency and procedural deficiencies within the pharmacist workforce.
METHODS: Clinical records of active opioid dependents who underwent MMT between 1 January 2007 and 31 March 2021 in Hospital Tuanku Fauziah, Perlis, Malaysia were retrospectively reviewed. Data collected included baseline demographics, history of illicit drug use, temporal trend in methadone dosage modulation, and co-use of illicit drugs during the MMT.
RESULTS: A total of 87 patients (mean age, 43.9 ± 8.33 years) were included. Their mean duration of involvement in MMT was 7.8 ± 3.69 years. The most commonly used drug was heroin (88.5%), followed by kratom (51.7%). Between 2019 and 2021, 61 (70.1%) patients had ceased abusing opioid, but 51 (58.6%) patients continued using any of the illicit drugs. Methamphetamine and amphetamine co-use was most common (n = 12, 37.5%). Hepatitis C status was not associated with the current methadone dose (U = 539.5, p = 0.186) or the highest dose required (t = -0.291, df = 74, p = 0.772). No predictor for illicit drug abstinence during MMT was identified. Methadone dose positively correlated with frequency of defaulting treatments (r = 0.22, p = 0.042).
CONCLUSION: Among our patients, MMT for opioid dependents cannot sufficiently curb illicit drug use, and there is a shift toward stimulants abuse.
MATERIALS AND METHODS: An online survey coupled with manual follow up was conducted throughout all MOH hospitals in Malaysia. Data collected described elements of the palliative care service(PCS) based on the WHO public health model. Data was computed using a novel matrix to determine three key indices which were the 1) palliative care development score (PCDS), 2)essential medications availability score (EMAS) and 3) opioid availability score (OAS). These scores then allowed mapping of PCS according to scores of 1-4 (1=least developed, 4=most developed).
FINDINGS: Out of all 140 MOH hospitals 88.6% (124) completed the PCDS survey, 120(85.7%) for the EMAS survey and 140 (100%) for the OAS survey. A total of 32(25.8%) hospitals had formal PCS with 8(25%) having resident palliative physicians (RPP), 8(25%) visiting palliative physicians(VPP) and 16(50%) no palliative physician (NPP). Out of these services, 17 (53%) had dedicated palliative care beds. In the PCDS survey, hospitals with PCS had significantly higher mean PCDS of 2.59 compared to 1.02 for non-PCS hospitals (P<0.001). The EMAS survey showed 109(90.8%) hospitals had EMAS of four and the OAS survey showed that 135(96.4%) hospitals had oral morphine available.
CONCLUSION: This study shows that palliative care service development in MOH hospitals is still very limited however, majority of MOH hospitals in Malaysia have all the essential medications and oral morphine available.
METHODS: This study prospectively evaluated mortality after prison release and whether methadone initiated before release increased survival after release in a sample of men with HIV and OUD (n = 291). We linked national death records to data from a controlled trial of prerelease methadone initiation conducted from 2010 to 2014 with men with HIV and OUD imprisoned in Malaysia. Vital statistics were collected through 2015. Allocation to prerelease methadone was by randomization (n = 64) and participant choice (n = 246). Cox proportional hazards models were used to estimate treatment effects of prerelease methadone on postrelease survival.
RESULTS: Overall, 62 deaths occurred over 872.5 person-years (PY) of postrelease follow-up, a crude mortality rate of 71.1 deaths per 1000 PY (95% confidence interval [CI] 54.5-89.4). Most deaths were of infectious etiology, mostly related to HIV. In a modified intention-to-treat analysis, the impact of prerelease methadone on postrelease mortality was consistent with a null effect in unadjusted (hazard ratio [HR] 1.3, 95% CI 0.6-3.1) and covariate-adjusted (HR 1.2, 95% CI 0.5-2.8) models. Predictors of mortality were educational level (HR 1.4, 95% CI 1.0-1.8), pre-incarceration alcohol use (HR 2.0, 95% CI 1.1-3.9), and lower CD4+ T-lymphocyte count (HR 0.8 per 100-cell/mL increase, 95% CI 0.7-1.0).
CONCLUSIONS: Postrelease mortality in this sample of men with HIV and OUD was extraordinarily high, and most deaths were likely of infectious etiology. No effect of prerelease methadone on postrelease mortality was observed, which may be due to study limitations or an epidemiological context in which inadequately treated HIV, and not inadequately treated OUD, is the main cause of death after prison release.
TRIAL REGISTRATION: NCT02396979. Retrospectively registered 24/03/2015.
METHOD: α-tocopherol monoester of MFA (TMMA) and α-tocopherol di-ester of MFA (TDMA) were synthesized by esterification reaction and were subjected to various in vivo characterizations.
RESULTS: Masking of the carboxylate group of MFA with the proposed pro-moieties significantly (p<0.05) delayed the onset of tonic-clonic seizure in mice. Besides, the intraperitoneal administration of TMMA and TDMA in mice produced significantly (p<0.05) stronger anti-inflammatory effects in the carrageenan-induced paw edema test and greater anti-nociceptive effect in the acetic acid-induced writhing test than MFA at an equimolar dose of 20 mg/kg. Treatment with TMMA and TDMA caused a significant (p<0.05) inhibition of pain at 1st and 2nd phases of formalin-induced licking test in mice, whereas treatment with MFA inhibited the 2nd phase only. Pretreatment with naloxone and flumazenil significantly (p<0.05) reversed the anti-nociceptive effect of MFA, TMMA and TDMA in the acetic acid-induced writhing test. In addition, treatment with TMMA and TDMA caused significantly (p<0.05) a higher inhibition of pain in the glutamate-induced licking response in mice than MFA.
CONCLUSION: Masking the carboxylate moiety of MFA by α-tocopherol and α-tocopherol acetate has a great potential for reducing CNS toxicity, enhancing the therapeutic efficacy and altering the mode of anti-nociceptive action.
AIM OF THE STUDY: To explore the antinociceptive (acute pain) and anti-neuropathic (chronic pain) activities of Lotus corniculatus leaves essential oil (LCEO) in addition to uncovering the possible mechanisms of antinociception.
MATERIALS AND METHODS: LCEO as well as the pure oleanolic acid (OA) compound, were assayed for their effects on acute (formalin induced paw licking test or FIPT) and chronic (cervical contusion injury models on the fifth cervical vertebra or CCS; 14-day intervals) pain. The possible involvements of NO-cGMP-K+ channel, TRPV, dopamine, cannabinoid, PPAR, adrenergic, and opioid mechanisms in the antinociceptive activity of LCEO have studied by formalin test. The levels of p53 and inflammatory markers were measured using a streptavidin biotin immune peroxidase complex and ELISA methods, respectively.
RESULTS: The LCEO and OA exerted antinociceptive activity in the first-phase of FIPT. Pretreatment with antagonists of TRPV1, dopamine D2, cannabinoid type1 and 2, and NO-cGMP-K+ channel blockers (glibenclamide, L-NAME and methylene blue) attenuated the antinociceptive effect of LCEO in FIPT. In addition, LCEO and OA meaningfully reduced hyperalgesia (days 6-14) and mechanical allodynia (days 2-14) in the CCS model. LCEO suppressed the apoptotic marker (p53) in CCS model and also ameliorated IL-2, TNF-α, and IL-1 in the spinal cord.
CONCLUSION: Finally, LCEO inhibited acute (possibly via the modulation of opioid, TRPV, dopamine, cannabinoid mechanisms as well as NO-cGMP-K+ channel) and chronic pain (via suppressing apoptotic and inflammatory markers) in male rats. The results also suggest that OA has analgesic activity against acute and chronic pain conditions.
OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023.
SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety.
AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.