The impact of family engagement in opioid assisted treatment: Results from a randomised controlled trial.

BACKGROUND: Family interventions in substance use disorders (SUD) treatment is limited despite the evidence for benefits. Providing family interventions is hampered by patient resistance, social stigma, logistics and factors related to the capacity of the treatment programmes. AIMS: The purpose of the study was to examine the association between family engagement in treatment, and opioid use defined by percentage negative opioid screen and rate retention in treatment defined by completion of study period. METHODS: Data from a 16-week outpatient randomised controlled trial (RCT) of 141 adults with opioid use disorder (OUD) receiving Opioid Assisted Treatment (OAT) using buprenorphine/naloxone film (BUP/NX-F) was, used to examine the association between family engagement in and opioid use and rate of retention in treatment. Multiple logistic regression was, applied to examine the independent prediction of family engagement on opioid use and rate retention in treatment. RESULTS: Family engagement was significantly associated with retention in treatment (Spearman's rho 0.25, p < 0.01) and was subsequently found to increase the likelihood of retention in treatment by approximately 3-fold (adjusted odds ratio (OR) 2.95, 95% CI 1.31-6.65). CONCLUSION: Family engagement in treatment is an independent predictor of retention in treatment but not opioid use in adults receiving OAT. It is, recommended that SUD treatment programmes integrate family related interventions in mainstream treatment. Delivering a personalised multicomponent family programme using digitised virtual communications that has been increasingly utilised during the Covid-19 pandemic is highly suggested.

Exploratory Economic Evaluation of Buprenorphine Treatment in Opioid Use Disorder.

BACKGROUND: Burden of opioid use disorder (OUD) is expressed in economic values or health metrics like Disability Adjusted Life Years (DALYs). Disability Weight (DW), a component of DALYs is estimated using economic methods or psychometric tools. Estimating DW at patient level using psychometric tools is an alternative to non-population specific DW overestimated by economic methods. Providing Medication Assisted Treatment (MAT) using buprenorphine/naloxone film (BUP/NX-F) for OUD is limited by financial constraints. AIM: To estimate the burden of OUD at patient level and explore the cost-benefit of two buprenorphine treatment interventions. METHODS: The present study was conducted alongside a randomized controlled trial of 141 adults with OUD stabilized on BUP/NX-F and randomized to BUP/NX-F with Incentivized Abstinence and Adherence Monitoring (experimental, n=70) and BUP/NX-F in usual care (control, n=71). The cost of illness was estimated applying a societal perspective. The Impairment Weight (IW) was estimated over a '0' to '1' scale, where '0' represents no impairment and '1' full impairment using the Work and Social Adjustment Scale (WSAS). RESULTS: Median (interquartile range) annual cost of OUD per participant was AED 498,171.1 (413,499.0 -635,725.3) and AED 538,694.4 (4,211,398.0 - 659,949.0) in the experimental and control groups, respectively (p=0.33). Illicit drug purchase represented 60 % of the annual cost of illness. At baseline, the mean Impairment Weight (IW) was 0.55 (SD 0.26) and 0.62 (SD 0.24) in the experimental and control groups, respectively. At end of the study, the IW was 0.26 (SD 0.28) representing 51% reduction in the experimental group compared to 0.42 (SD 0.33) in the control group representing a 27% reduction. Excluding imprisonment, the cost-benefit of treatment was not realized. In contrast, accounting for imprisonment, cost benefit expressed as a return-on-investment was established at 1.55 and 1.29 in the experimental and control groups, respectively. IMPLICATIONS FOR MENTAL HEALTH POLICY: Cost benefit analysis can serve as a simple and practical tool to evaluate the cost benefit of treatment interventions. Demonstrating the cost benefit of buprenorphine treatment has the potential to facilitate public funding and accessibility to opioid assisted treatment.

Factor VIII Intron 22 Inversion in Severe Hemophilia A Patients in Palestine.

BACKGROUND: Hemophilia A is an X-linked recessive bleeding disorder caused by mutations in FVIII gene with an incidence of 1 in 5,000 to 10,000 live born males. The Inv22 mutation is a major cause of the disease worldwide, accounting for up to 40%-50% of severe FVIII mutations. The aim of the present study was to screen Inv22 of the FVIII gene in Palestinian patients with severe HA and reveal its role as a predisposing factor for the development of inhibitors. MATERIALS AND METHODS: A cohort of 77 HA individuals including 5 carrier females from 52 unrelated families registered at governmental hemophilia centers in the West Bank area of Palestine was investigated. The demographic data and the clinical history were retrieved from medical files. Molecular analysis of Inv22 mutation in severe HA (30 cases) from Palestine was performed using the subcycling polymerase reaction (S-PCR). FVIII coagulant activities were carried out on an aPTT-based 1-stage clotting assay. FVIII inhibitors were quantified using the Nijmegen modification of the Bethesda assay. RESULT: Overall, 41.7% (30/72) of the studied cases were classified as having severe HA, 22.2% (16/72) had moderate HA, and 36.1% (26/72) had mild HA. Five randomly selected carrier mothers were screened for the Inv22 mutation to confirm its transmission to their sons. The Inv22 mutation was detected in 11 severe HA patients (36.6%). Among the severe HA patients with positive Inv22, 45.5% (5/11) had developed inhibitors. The current study showed that there was no association (p=0.53) between inhibitor development and the Inv22 mutation. CONCLUSION: Findings on Inv22 are in agreement with worldwide reports, being a major genetic mutation in severe HA. The S-PCR is a simple, rapid, and cost-effective method for the diagnosis of Inv22 in severe HA patients. Although the Inv22 mutation was associated with 36.6% of severe HA phenotype cases, it was not a major predisposing factor for inhibitor formation.

Anti-Inflammatory and Anticoagulant Activities of Synthesized NSAID Prodrug Esters.

Paracetamol with ibuprofen or with naproxen are frequently prescribed by doctors in combination. It was found that patients using a combination of NSAID like acetaminophen and ibuprofen experienced less pain. Patients are more compliant if these two drugs are combined in an ester form and given in one dosage form. The esterified prodrugs are hydrolyzed in humans to their active forms. In this study, two esters of paracetamol combined with ibuprofen and naproxen were synthesized as prodrugs. The physiochemical properties of these products were identified. Moreover, the bioactivities of these prodrugs were tested for its anti-inflammatory and anticoagulant activities. The results showed an improved COX inhibition and anticoagulant activity compared with their parent drugs. The synthesized drugs are expected to improve patient's compliance in terms of administration frequency and will have better pharmacokinetic properties with fewer side effects.

Therapeutic Drug Monitoring in Buprenorphine/Naloxone Treatment for Opioid Use Disorder: Clinical Feasibility and Optimizing Assay Precision.

INTRODUCTION: Compliance with sublingual buprenorphine/naloxone (SL-BUP/NX) is associated with higher abstinence from illicit opioid use. Therapeutic drug monitoring (TDM) has been recommended for adherence monitoring of buprenorphine (BUP) maintenance treatment for opioid use disorder (OUD), but to date there have been no reported clinical applications. In this TDM feasibility study, we investigated BUP assay precision in 15 adults with OUD who had been stabilized on buprenorphine/naloxone. METHODS: Using solid phase extraction, BUP recovery was contrasted at 100 mMol and 1 Molar of acetic acid wash solution. Precision was determined by applying the condition generating highest recovery using 0.2 ng/mL and 10 ng/mL standards. Four blood samples were drawn to examine the BUP peak and trough plasma concentrations, and BUP elimination rate was estimated. BUP recovery was examined again in a random sample and contrasted with the concentration predicted applying first-order kinetics. RESULTS: Higher BUP recovery was achieved with 1 Molar wash (94.3%; p=0.05). Precision ranged from 15-20%. The estimated limit of detection (LoD) and limit of quantitation (LoQ) were 0.02 and 0.069 ng/mL, respectively. BUP peak and trough concentrations were successfully examined, and BUP trough concentrations were replicated confirming steady state. BUP concentrations were predicted at a variance of -7.20% to 1.54 %. CONCLUSIONS: TDM for BUP maintenance treatment of OUD is feasible, and simple adjustment of the assay conditions enhances BUP recovery.

Suboxone Treatment and Recovery Trial (STAR-T): Study Protocol for a Randomised Controlled Trial of Opioid Medication Assisted Treatment with Adjunctive Medication Management Using Therapeutic Drug Monitoring and Contingency Management.

INTRODUCTION: Opioid assisted treatment (OAT) with buprenorphine (BUP) is front-line medical maintenance intervention for illicit and prescription opioid use disorder (OUD). In many clinics, opioid medication is dispensed for several days for self-administration. This provides flexibility to the patient but may compromise the effectiveness of OAT because of nonadherence or medication diversion. OAT can be delivered as an entirely supervised intervention, but many patients discontinue treatment under this arrangement and dispensing costs may be prohibitive. An alternative is to enable patients to receive take-home doses contingent on OAT adherence guided by a medication management framework using Therapeutic Drug Monitoring (TDM) alongside negative urine drug screens (UDS) to provide evidence of abstinence. TDM is recommended to monitor adherence with BUP but it has not been applied in OAT programs and evaluation research to date. METHODS: The Suboxone Treatment and Recovery Trial (STAR-T) is a single site, 16-week, parallel-group, randomised controlled trial. The aim of the study is to determine the effectiveness of a medication management framework including TDM and UDS to enable patients enrolled on outpatient OAT (with buprenorphine/naloxone [sublingual film formulation; BUP/NX-F; Suboxone™]) to receive stepped take-home doses. Following stabilisation during inpatient care, adult participants with illicit or prescription OUD were allocated (1:1) to receive (1) BUP/NX-F plus medication management for take-home doses based on TDM, UDS, and contingency management protocol (the experimental group) or (2) BUP/NX-F plus UDS only (treatment-as-usual, the control group). The primary outcome is the mean percentage of negative UDS over 16 weeks. The secondary outcome is treatment retention defined as completion of 16 weeks of OAT without interruption. There will be an exploratory analysis of the association between participant characteristics, clinical data, and outcomes. CONCLUSIONS: Providing BUP/NX-F take-home doses contingent on adherence and opioid abstinence may enable OAT to be delivered flexibly and effectively. TRIAL REGISTRATION: ISRCTN41645723 is retrospectively registered on 15/11/2015.

Macrolide and lincosamide resistance in staphylococcal clinical isolates in Nablus, Palestine.

BACKGROUND/AIM: Macrolide and lincosamide antibiotics are used for the treatment of staphylococcal infections, especially for penicillin-allergic patients. In the present study, we evaluate the prevalence of resistance to macrolide and lincosamide antibiotics among staphylococci isolates. MATERIALS AND METHODS: A total of 200 staphylococcal clinical isolates were collected from January 2012 to April 2013. Minimal inhibitory concentrations of erythromycin and clindamycin were determined by agar dilution method. An erythromycin-clindamycin induction test was performed for isolates that were only resistant to erythromycin. Representative erythromycin-resistant isolates were examined for erythromycin resistance genes using PCR. RESULTS: Among staphylococci isolates, resistance frequencies of erythromycin and clindamycin were 65.5% and 20.5%, respectively. Erythromycin resistance was found to be mediated by putative efflux (50.4%) and target site modification (49.6%). Inducible target site modification resistance was detected in 19.1% of erythromycin-resistant isolates. Among the examined 36 staphylococci isolates, msr(A), erm(C), erm(A), and mef(A/E) genes were detected in 55.6%, 30.6%, 25%, and 0%, respectively. CONCLUSION: Results of the current study indicate the presence of high rates of macrolide resistance and inducible phenotypes among staphylococcal isolates. It is also essential to keep in mind variations of resistance rates among various age groups and specimen types.

Levodopa-Carbidopa Intestinal Gel Infusion Therapy in Advanced Parkinson's Disease: Single Middle Eastern Center Experience.

BACKGROUND: Levodopa therapy in Parkinson's disease (PD) is often associated with disabling motor and non-motor complications in patients with advanced disease due to the variable absorption of levodopa because of an irregular or erratic emptying of the gastric content. METHODS: Prospective single movement disorder center study using pre-set selection criteria, unified PD scale (UPDRS III), non-motor symptoms scale (NMSS), and PD questionnaire-8 (PDQ-8) to evaluate the efficacy, safety, and long-term treatment outcomes using levodopa-carbidopa intestinal gel (LCIG) infusion in patients with advanced PD, who were followed up every 6 months. RESULTS: Twenty patients were recruited over a period of 6 years. Disease duration prior to LCIG infusion ranged from 5 to 18 years (mean 11.4 ± 4.2). The mean follow-up time on LCIG therapy was 48.5 ± 23.2 months (range 11-83 months). Mean 'off' time, UPDRS III, NMSS, and PDQ-8 improvement were statistically significant. Two patients dropped out and 66.7% of patients required tube replacement. CONCLUSION: LCIG infusion monotherapy demonstrated significant improvement in reducing the 'off' time, reducing levodopa-induced dyskinesia, and improving non-motor symptoms and quality of life. This therapy is recommended for patients in whom motor fluctuations are inadequately treated with traditional oral PD therapy.

Sudanese refugees: sufferings and suggested management.

Egypt and the Sudan have historically provided a continuum of social and cultural exchange. With the Nile valley providing the only route between the Mediterranean and sub-Saharan Africa, Egypt became the natural host for Sudanese refugees.

The effect of soft-tissue ultrasound on the management of cellulitis in the emergency department.

OBJECTIVES: To evaluate the effect of diagnostic soft-tissue ultrasound (US) on management of emergency department (ED) patients with clinical cellulitis. METHODS: This was a prospective observational study in an urban ED of adult patients with clinical soft-tissue infection without obvious abscess. The treating physician's pretest opinions regarding the need for further drainage procedures and the probability of subcutaneous fluid collection were determined. Emergency sonologists then performed US of the infected area, and the effect on management plan was recorded. RESULTS: Ultrasound changed the management of patients with cellulitis in 71/126 (56%) of cases. In the pretest group that was believed not to need further drainage, US changed the management in 39/82 (48%), with 33 receiving drainage and 6 receiving further diagnostics or consultation. In the pretest group in which further drainage was believed to be needed, US changed the management in 32/44 (73%), including 16 in whom drainage was eliminated and 16 who had further diagnostic interventions. US had a management effect in all pretest probabilities for fluid from 10% to 90%. CONCLUSIONS: Soft-tissue US changes physician management in approximately half of patients in the ED with clinical cellulitis. US may guide management of cellulitis by detection of occult abscess, prevention of invasive procedures, and guidance for further imaging or consultation.

Nontraumatic out-of-hospital hypotension predicts inhospital mortality.

STUDY OBJECTIVE: Out-of-hospital hypotension may signify need for intensive resuscitation and rapid diagnosis on emergency department (ED) arrival. We hypothesized that nontraumatic out-of-hospital hypotension confers risk of inhospital mortality. METHODS: This was a multicenter study of ambulance-transported, nontrauma, non-cardiopulmonary resuscitation patients conducted at 2 venues: (1) a cross-sectional risk assessment study of high-priority medical transports at a US metropolitan county; and (2) a Canadian prospective multicenter cohort study of patients with respiratory distress. Data at both venues were extracted from prospectively recorded, standardized run sheets by either a physician or a paramedic. Data extraction and analysis at each venue were conducted independently. Exposures to hypotension were defined as age older than 17 years old, systolic blood pressure less than 100 mm Hg during transport, and 1 or more of 10 predefined symptoms of circulatory insufficiency. Nonexposures to hypotension had the same definition as exposures, except the systolic blood pressure had to be more than 100 mm Hg during the entire out-of-hospital transport. The main outcome variable was inhospital mortality. RESULTS: At venue 1, of 3,128 transports, 395 (13%) exposures and 395 nonexposures were identified. Inhospital mortality of exposures was 26% versus 8% for nonexposures (adjusted odds ratio [OR] 4.6; 95% confidence interval [CI] 2.0 to 5.9). At venue 2, of 7,679 transports, 532 exposures (7%) and 7,147 nonexposures were identified. Out-of-hospital exposure to hypotension conferred a mortality rate of 32% versus 11% for nonexposures (OR 3.0; 95% CI 2.4 to 3.7), representing a sensitivity of 18% and a specificity of 95%. CONCLUSION: The inhospital mortality rate after out-of-hospital, nontraumatic hypotension is high and reproducible. Future research should focus on ED clinical protocols to ensure appropriate resuscitation and investigation of etiology of out-of-hospital hypotension.