Patient's and healthcare provider's experiences with Opioid Maintenance Treatment (OMT): a qualitative evidence synthesis.

BACKGROUND: Opioid Maintenance Treatment (OMT) is the gold standard for people with opioid dependence. However, drop-out rates are high, and many patients do not reach desired outcomes. Understanding patients' and healthcare providers' experiences with the treatment can provide valuable information to improve the quality of OMT and to increase acceptability and accessibility of services. The aim of this systematic review is to explore and synthesise the experiences of OMT among persons with opioid dependence and health care providers, to inform policy makers and practitioners on how to improve OMT outcomes. METHODS: We conducted a qualitative evidence synthesis. We systematically searched in electronic databases (CINAHL, Embase, MEDLINE, and nordic databases) and searched for grey literature. As we identified many studies that met our inclusion criteria, we purposively sampled a manageable number of studies to include in this review. Two researchers independently extracted and coded data from the included studies and used the Andersen's healthcare utilization model to organize and develop codes. We assessed the methodological limitations of the studies, and our confidence in the findings using GRADE CERQual. RESULTS: We retrieved 56 relevant studies and purposively sampled 24 qualitative studies of patients' and healthcare providers' experiences with OMT. Our analyses resulted in six main themes: (1) External stigma prevents engagement and retention in treatment, (2) Being identified as in OMT contributed to an increased experience of stigma (3) Inadequate knowledge and expertise among healthcare providers affected patients' treatment experiences, (4) Quality of communication between personnel and patients impacts patients' engagement with treatment and treatment outcomes, (5) Patients wanted help with many aspects of their lives not just medication, and (6) Balancing positive expectations of OMT with treatment stigma. We found that stigma was an overarching theme across these themes. CONCLUSION: Our findings suggest that OMT could be more beneficial for patients if treatment programs prioritize efforts to diminish societal and OMT provider stigma and find strategies to better address patient needs. Initiatives should focus on improving treatment knowledge among providers, encouraging the use of client perspectives, considering the context of family members, and establishing a more holistic and flexible treatment environment.

Metabolic and functional substrates of impulsive decision-making in individuals with heroin addiction after prolonged methadone maintenance treatment.

Elevated impulsivity has been frequently reported in individuals with opioid addiction receiving methadone maintenance therapy (MMT), but the underlying neural mechanisms and cognitive subprocesses are not fully understood. We acquired functional magnetic resonance imaging (fMRI) data from 37 subjects with heroin addiction receiving long-term MMT and 33 healthy controls who performed a probabilistic reversal learning task, and measured their resting-state brain glucose using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Subjects receiving MMT exhibited significantly elevated self-reported impulsivity, and computational modeling revealed a marked impulsive decision bias manifested as switching more frequently without available evidence. Moreover, this impulsive decision bias was associated with the dose and duration of methadone use, irrelevant to the duration of heroin use. During the task, the switch-related hypoactivation in the left rostral middle frontal gyrus was correlated with the impulsive decision bias while the function of reward sensitivity was intact in subjects receiving MMT. Using prior brain-wide receptor density data, we found that the highest variance of regional metabolic abnormalities was explained by the spatial distribution of µ-opioid receptors among 10 types of neurotransmitter receptors. Heightened impulsivity in individuals receiving prolonged MMT is manifested as atypical choice bias and noise in decision-making processes, which is further driven by deficits in top-down cognitive control, other than reward sensitivity. Our findings uncover multifaceted mechanisms underlying elevated impulsivity in subjects receiving MMT, which might provide insights for developing complementary therapies to improve retention during MMT.

Stigma and level of familiarity with opioid maintenance treatment (OMT) among specialist physicians in Israel.

CONTEXT: Opioid use disorder (OUD) poses significant public health problems that have increased dramatically, resulting in high rates of morbidity and mortality. OBJECTIVES: To minimize the risk of an opioid epidemic in Israel and be prepared, we evaluated physicians' objective knowledge, level of stigma, and approach to prescribing opioids, risk factors, and identification of patients with substance use disorder (SUD), as well as their knowledge about opioid maintenance treatment (OMT) for OUD. METHODS: Anonymous computerized questionnaires were distributed nationally to physicians by the Israel Medical Association. Knowledge, stigma, and approach were scored. RESULTS: Of only 249 responders, 58.6% prescribe opioids, 32.1% prescribe cannabis, and 18.5% daily encounter patients with SUD. Logistic regression found the high knowledge group had daily encounters with SUD (Odds Ratio (OR) = 3.5, 95% CI 1.7-7.1) and were familiar with OMT (OR = 10.1, 95% CI 3.5-29.0). The high stigma group was characterized by physicians who prescribe opioids (OR = 1.7, 95% CI 1.0-2.9), but who self-reported having limited knowledge regarding OMT (OR = 2, 95% CI 1.1-3.7). The high approach group was characterized by those who prescribe opioids (OR = 11.7, 95% CI 4.9-28), prescribe cannabis (OR = 2.1, 95% CI 1.0-4.3), self-report having limited knowledge regarding OMT (OR = 11.2, 95% CI 1.4-89) and self-report identifying SUD (OR = 32.5, 95% CI 4.1-260). CONCLUSION: High stigma was most evident among physicians who prescribe opioids but, importantly, who had limited knowledge specifically regarding OMT. Gaps in knowledge and approach were observed. An educational intervention is highly recommended to reduce stigma and increase referrals of patients for OMT, the most effective treatment for opioid use disorder.

The effect of multivitamins on anxiety and depression in patients undergoing methadone maintenance treatment: A double-blind randomized controlled trial.

BACKGROUND: The prevalence of addiction is increasing in the world. Methadone Maintenance Treatment (MMT) can be associated with severe stress and mild to moderate depressive symptoms. Vitamins and minerals are commonly found in multivitamins seem to improve mood. Therefore, the aim of this study was to evaluate the effect of multivitamins on anxiety and depression in patients undergoing MMT in a double-blind randomized controlled trial. METHODS: The study was designed as a double-blind, randomized controlled trial and involved 70 male MMT patients over the age of 18. Participants were randomized to one of two groups, either those receiving multivitamins or those receiving a placebo for 12 weeks. The multivitamin capsule included vitamin E, B1, B2, B3, B5, B6, B12, C, biotin, folic acid, and zinc. Anxiety and depression were measured using standard questionnaires, before and after the intervention. RESULTS: The between-group comparison (i.e., intervention vs. placebo) indicated there was no significant difference in anxiety scores; however, there was a significant between-group difference in depression scores, favoring the intervention group. CONCLUSIONS: Multivitamin supplementation improved depression but did not have a significant impact on anxiety in patients undergoing MMT.

Investigating the effect of zinc supplementation on probability of relapse and mental health in patients with opioid use disorder undergoing methadone maintenance treatment.

BACKGROUND: Considering different factors, such as high withdrawal rates in methadone maintenance treatment (MMT) programs alongside mental health (MH) problems appearing in patients with opioid use disorder and the lack of prior research on the effect of zinc supplementation in this respect, the present study aimed to investigate the effect of zinc supplementation on the probability of relapse (PoR) and MH problems in patients with opioid use disorder undergoing MMT. METHODS: For this purpose, a randomized controlled trial with a clinical basis was fulfilled on a total of 68 patients with opioid use disorder receiving MMT, allocated to two groups, viz. intervention, and control (each one consisting of 34 individuals). Then, the participants in the intervention group were given zinc supplements combined with methadone for three months, and the controls only took methadone, according to the treatment plan. The data were collected using the Relapse Prediction Scale (RPS) and the Depression, Anxiety, and Stress Scale 21 (DASS-21) before, one month after, and at the end of the intervention program. FINDINGS: Compared to the control group, the likelihood of drug use (p = 0.01), drug craving (p = 0.002), and the RPS total score (p = 0.002) in the intervention group was significantly lower. Moreover, the results revealed a significant decreasing trend in depression (p = 0.01), anxiety (p < 0.001), stress (p = 0.001), and the DASS-21 total score (p = 0.001) in the intervention. Compared to the control group, the DASS-21 total score (p < 0.001) in the intervention group was significantly lower. CONCLUSION: Accordingly, it was concluded that zinc supplementation could reduce the PoR and improve MH problems in patients with opioid use disorder experiencing MMT. However, further research is recommended to fill the gaps. TRIAL REGISTRATION: The research protocol has also been listed on the Iranian Registry of Clinical Trials (IRCT) with code no. IRCT2020050904736N1.

Decision tree model based prediction of the efficacy of acupuncture in methadone maintenance treatment.

Background: Patients with MMT often face difficulties such as sleep disturbance, headaches, and difficulty in complete abstinence from drugs. Research has shown that acupuncture can mitigate side effects while attenuating methadone dependence. It also has a synergistic and attenuated effect on methadone maintenance treatment (MMT). Exploring the predictors of the efficacy of acupuncture intervention in MMT might help clinicians and patients promote acupuncture-assisted participation in MMT, and improve clinical treatment strategies for MMT. Objective: To describe the effect of potential predictors on MMT after acupuncture intervention by building a decision-tree model of data from A Clinical Study of Acupuncture-assisted MMT. Design setting and participants: In this randomized controlled trial, 135 patients with MMT underwent acupuncture at the Substance Dependence Department of Guangzhou Huiai Hospital in Guangzhou, Guangdong Province, China. Intervention: A total of 135 patients were 1:1 randomly assigned to either an acupuncture plus routine care group (acupuncture plus methadone) or a routine group (methadone only) for 6 weeks, and followed up for 10 weeks. Sex, age, education level, route of previous opioid use, years of opioid use, and MMT time were recorded before the trial. Outcome measurements and statistical analysis: All analyses were based on the intention-to-treat (ITT) population. The two decision tree models used the change of methadone dosage and the VAS score for opioid desire as response variables, respectively, and the evaluation criteria were positive effect (decreased by ≥20%) and no effect (decreased by <20%, or increased). We generated the respective feature weights for the decision tree and evaluated the model's accuracy and performance by Precision-Recall. Results: The overall accuracy of methadone reduction and psychological craving VAS scoring decision trees were 0.63 and 0.74, respectively. The Methadone Dosage Efficacy decision tree identified years of opioid use (weight = 0.348), acupuncture (weight = 0.346), and route of previous opioid use (weight = 0.162) as key features. For the VAS Score decision tree, acupuncture (weight = 0.618), MMT time (weight = 0.235), and age (weight = 0.043) were the important features. Conclusion: Exploratory decision tree analysis showed that acupuncture, years of opioid use, route of previous opioid use, MMT time, and age were key predictors of the MMT treatment. Thus, acupuncture-assisted MMT strategy should consider the relevant influencing factors mentioned above. Patient summary: Understanding patient characteristics and the impact of acupuncture regimens on methadone dosage reduction in MMT patients may help physicians determine the best treatment regimen for patients. An analysis of data from our clinical trial showed that acupuncture, years of opioid use, route of previous opioid use, age, and MMT time were key predictors of progressive recovery in patients with MMT. Eligible patients may benefit most from the MMT rehabilitation that reduces consumption and psychological cravings for methadone. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR1900026357.

[Long-term efficacy evaluation of coated metal stent implantation for ureteroscopic lithotripsy related refractory ureteral stricture].

OBJECTIVE: To comprehensively evaluate the long-term efficacy and safety of coated metal stent implantation for ureteroscopic lithotripsy related refractory ureteral stricture (URL-rUS). METHODS: Electronic medical records of 30 patients (31 affected renal units) receiving coated metal stent implantation for URL-rUS from Sept. 2018 to Aug. 2021 at Peking University People' s Hospital were reviewed for analysis. Coated metal stents were implanted in retrograde approach via ureteroscope. Last outpatient follow-up was set as endpoint. Baseline information, stricture characteristics and decompression strategy before coated metal stent implantation were retrospectively collected. Serum creatinine (Scr) concentration and renal pelvis width (RPW) were used as renal function indicators. Peri-operative and long-term complications and according outcomes were recorded. For the patients who had double J tubes implanted for drainage before operation, Ureteral Stent Symptom Questionnaire (USSQ) was applied to evaluate the stent-related discomforts and quality of life (QoL) before and after surgery. Data analysis was conducted with SPSS (version 25.0; SPSS, Chicago, IL, USA). RESULTS: Totally 30 patients with 31 affected renal units were included. All the patients previously underwent unsuccessful traditional endoscopic balloon dilation or endoureterotomy before receiving coated metal stent implantation. The mean age was (45.5±9.3) years old. The median follow-up time were 14 (6-36) months. All coated metal stents were successfully placed with a median duration of 60 (30-195) min. No severe peri-operative complications occurred. At endpoint, 28 (90.3%) sides of coated metal stents remained unobstructed with a longest indwelling time of 36 months. Causes of failures included stent migration (1 case, 3.2%), encrustation (1 case, 3.2%) and repeated stent related urinary tract infection (1 case, 3.2%). When compared with the baseline, significant reductions were observed in both Scr concentration and RPW at endpoint [(90.7±19.5) mmol/L vs. (83.1±18.5) µmol/L, P < 0.01, for Scr; (2.5±1.3) cm vs. (1.9±0.8) cm, P < 0.01, for RPW], indicating good preservation of renal function and remission of hydronephrosis. For 26 patients with double J stents before operation, significant reduction of USSQ average score (100.4±6.6 vs. 82.1±4.9, P < 0.01) evidenced better life quality preserving ability of coated metal stent versus double J stent. CONCLUSION: Coated metal stent implantation is a safe and minimally invasive management of ureteral stricture providing a satisfying long-term patency rate, after which the patients' quality of life and renal function could be both improved. This method could serve as a promising alternative long-term maintenance treatment option for patients with URL-US, especially when traditional endoscopic interventions failed.

Laser meridian massage decreased craving in men with opioid use disorder on methadone maintenance treatment.

BACKGROUND: The incidence of opioid use disorder (OUD) is increasing worldwide, and the opioid-related overdose crisis is currently a major global challenge. This study investigated the effects of adjuvant laser meridian massage (LMM) in men with OUD undergoing methadone maintenance treatment (MMT). METHODS: A case-controlled study was conducted from February 2019 to April 2020. Fourteen men with OUD on MMT were enrolled from an addiction treatment center as an experimental group. An age-matched control group comprising 13 men was also enrolled. The experimental group received LMM on the back, including over the Bladder meridian and Governor Vessel, three times weekly for 4 weeks. The control group received only MMT. Urinary morphine levels, patients' self-reports of the number of episodes or days of heroin use, and visual analog scale scores for heroin craving/refusal to use heroin during the previous week were evaluated. Quality of life was reported using the Short Form (SF)-12v2. RESULTS: The experimental group showed a significant decrease in heroin use (p < 0.05), whereas the control group showed a significant increase in heroin craving (p < 0.05). The SF-12v2 Health Survey revealed a significant improvement in physical health in the experimental group (P < 0.05). CONCLUSION: The results of this study suggest that laser meridian massage can be considered a safe, well-tolerated, and potentially useful adjuvant intervention for opioid use disorder.

Cannabis use is associated with lower retention in methadone maintenance treatment, but not among schizophrenic- and other chronically psychotic patients.

The findings of studies on cannabis use and retention in methadone maintenance treatment (MMT) are inconsistent.To study cannabis use and its relationship to patients' outcomes in MMT with/without lifetime DSM-IV-TR schizophrenia/chronic-psychosis diagnosis.Since June 1993, 877 patients with available lifetime DSM-IV-TR psychiatric diagnosis were followed-up until December 2017. Urine drug screens on admission and after one year were analyzed.Lifetime schizophrenia/psychosis was diagnosed in 50 (5.7%) patients. They did not differ from the other 827 by admission cannabis use (18.0% vs. 12.3%) and had similar 1-year retention rates (76.0% vs.77.0%, respectively). Cumulative retention of the cohort excluding schizophrenia/chronic-psychosis was longer for the 667 patients who did not use cannabis after 1-year (9.1 years, 95%CI 8.4-9.9) compared with the 118 cannabis-users after 1-year (6.0 years, 95% CI 4.8-7.2, p<.001). Among the schizophrenia/chronic-psychosis group, cannabis was not related to retention (38 non-users, 7.9 years 95%CI 5.2-10.5 vs. 9 cannabis-users, 9.9 years, 95% CI 3.8-16.0, p=.5). Survival was shorter for the 41 schizophrenia/chronic-psychosis non-users (15.2 years, 95% CI 12.8-17.7) than for the 719 non-schizophrenia/chronic-psychosis non-users (18.5, 95%CI 17.9-19.2, p = 0.009). However, survival was comparable among the 9 cannabis-users with schizophrenia/chronic-psychosis (20.1, 95% CI 16.2-24.1) and 101 other cohort users (18.6, 95% CI 16.9-20.4).Cannabis use is associated with decreased retention among MMT patients, however the effects of cannabis on schizophrenia/psychosis patients on retention and survival cannot be verified due to the small sample size and the limited data regarding chronicity of cannabis use. Future larger, prospective studies are needed.

Different Approach to Manage Demodex Blepharitis - Initial and Maintenance Treatment.

PURPOSE/AIM OF THE STUDY: To evaluate the improvement of ocular signs and symptoms in patients suffering from Demodex blepharitis using a combined treatment approach: use of eyelid wipes impregnated with 2.5% terpinen-4-ol (T4O) and 0.2% hyaluronic acid (HA) in the initial treatment period and investigation of maintenance of the treatment effect with the use of eyelid cleansing wipes. MATERIALS AND METHODS: Fifty patients with Demodex blepharitis were treated in the initial treatment period with sterile eyelid T4O impregnated wipes for 28 days. In the following four-week maintenance period, 82% patients received sterile eyelid maintenance wipes, while 16% continued treatment with T4O impregnated wipes. Global ocular discomfort, adapted TOSS, SANDE score, and individual blepharitis symptoms were assessed by patients at day 28 and day 56. Ocular signs were evaluated by the investigator at the study visits. Investigator's assessment of the overall treatment performance, patient's assessment of treatment satisfaction, and tolerability were evaluated with questionnaires. RESULTS: All global ocular discomfort symptoms and disease specific symptoms assessed by patients as well as all parameters evaluated by the investigators significantly improved in the initial treatment period with the application of eyelid wipes impregnated with 2.5% terpinen-4-ol until day 28. The therapeutic effect was maintained or even improved during the maintenance period under administration of mainly eyelid maintenance wipes until day 56. Both products were well tolerated. No adverse events and no clinically relevant changes in visual acuity were observed during both periods. CONCLUSIONS: Once daily treatment with T4O impregnated eyelid wipes in the initial treatment period significantly improved the ocular symptoms and signs and reduced the mite count in patients with Demodex blepharitis within four-weeks administration. Subsequent maintenance treatment with maintenance wipes for another 4 weeks preserved or further intensified the treatment success. The products were well tolerated and were convenient to use.

Acupuncture for Opioid Dependence Patients Receiving Methadone Maintenance Treatment: A Network Meta-Analysis.

Objectives: Opioid dependence has been a threat to public health for hundreds of years. With the increasing number of studies on acupuncture-related therapies for opioid dependence patients receiving methadone maintenance treatment (MMT), its effect of acupuncture therapy in treating MMT patients remains controversial. Therefore, we conducted a multiple-treatments meta-analysis, and incorporated both direct and indirect comparisons, in order to discover the most effective treatment for opioid dependence patients receiving MMT. Methods: Five English databases and three Chinese databases were searched from its inception to August 20, 2020, in order to compare the effects of acupuncture-related therapies and MMT, which was summarized as Western medicine (WM) in the following texts. The quality of studies was assessed according to Cochrane's risk of bias tool 5.1.0, and a pair-wise meta-analysis, cumulative meta-analysis, and the network meta-analysis was performed using the R software (Version 3.6.1) and STATA (Version 14.0). The primary outcome was the effective rate, which was calculated by the ratio of detoxifying patients to the total. The secondary outcome was the Modified Himmelsbach Opiate Withdrawal Scale (MHOWS). Results: A total of 20 trials were included, which consisted of comparisons among WM, traditional Chinese medicine (TCM), and the four types of acupuncture, namely, manual acupuncture (MA), electro-acupuncture (EA), auricular acupuncture (AA), and transcutaneous electrical acupoint stimulation (TEAS). Though none of the trials were at low risk of bias. In the pair-wise meta-analysis, no statistically significant differences were observed in terms of the effective rate. Furthermore, MA was more efficacious than WM, EA, and TEAS in MHOWS, with mean differences (MDs) of (-8.59, 95% CI: -15.96 to -1.23, P < 0.01), (-6.15, 95% CI: -9.45 to -2.85, P < 0.05), and (-10.44, 95% CI: -16.11 to -4.77, P < 0.05), respectively. In the network meta-analysis, MA was more effective than WM (RR: 1.40, 95% CI: 1.05 to 1.99) on the effective rate, and (MD: -5.74, 95% CI: -11.60 to -0.10) on MHOWS. TEAS was more effective than WM (MD: -15.34, 95% CI: -27.34 to -3.46) on MHOWS. Synthetically, MA had the highest probability to rank first in treating opioid dependence. Conclusions: The existing evidence shows that acupuncture related-therapies may effectively be used for treating patients receiving MMT, and that manual acupuncture may be the best choice for opioid dependence among all kinds of acupuncture-related therapies. Nevertheless, reducing the relapse and promoting the recovery of opioid dependence need more efforts from not only the medical industry but also government support, security system, and educational popularization. To strengthen the assurance of acupuncture-related therapies in the treatment of opioid dependence, we expected that clinical trials with high quality would be conducted, to provide more confident evidence.

"Highly Exposed Chinese Herbal Medicine" Combined With Apatinib as Maintenance Treatment Following First-Line or Second-Line Chemotherapy for Extensive-Stage Small-Cell Lung Cancer: A Single-Arm, Prospective Study.

This study aimed to evaluate the efficacy and safety of "highly exposed Chinese herbal medicine" combined with apatinib as maintenance treatment following first-line or second-line chemotherapy in patients with ES-SCLC. A total of 23 patients with ES-SCLC were included in this single-arm prospective study (ChiCTR2100045255). "Highly exposed Chinese herbal medicine" combined with apatinib was administered each day after the chemotherapy for maintenance treatment. The primary endpoint of the study was median PFS, while the secondary endpoints included median OS, DCR, ORR, AE, and the association of "highly exposed Chinese herbal medicine" with PFS and OS. Three and 16 patients achieved partial response (PR) and stable disease (SD), respectively, and four patients were with disease progression (PD). The ORR of the patients was 13.0%, DCR was 83.0%, median PFS was 5.0 months, and median OS was 18.0 months. The major AE included secondary hypertension and hand-foot syndrome. Oral intake of Chinese herbal medicine for ≥ 6 months was associated with longer PFS. Hand-foot syndrome was an independent predictive factor for PFS. The statistical analysis suggested no independent influencing factors for OS. "Highly exposed Chinese herbal medicine" combined with apatinib is effective and relatively safe as the maintenance treatment for ES-SCLC patients who undergo first-line or second-line chemotherapy.

Aclidinium bromide/formoterol fumarate as a treatment for COPD: an update.

Introduction: Aclidinium/formoterol is a long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) dual bronchodilator used as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The efficacy of aclidinium/formoterol has been demonstrated consistently in patients with moderate-to-severe COPD versus placebo and monocomponents, with a comparable safety profile.Areas covered: This review examines recent research findings that expand our understanding of the impact of aclidinium/formoterol on the burden of COPD. Reviewed outcomes include improvements in lung function, respiratory symptoms, health-related quality of life, exercise tolerance, exacerbation rates, and clinically important deteriorations. In addition, the reported cardiovascular safety of aclidinium and current LAMA/LABA treatment recommendations are discussed.Expert opinion: Aclidinium/formoterol reduces disease burden in patients with COPD, including those that are treatment-naïve, without a significant increase in safety risk compared with monotherapies. Furthermore, evidence supports an improvement in lung function over a 24-hour period with aclidinium/formoterol treatment versus monotherapy and placebo, which may offer an advantage over some once-daily LAMA/LABA combinations. In summary, the recent evidence discussed in this review adds weight to the use of LAMA/LABA combinations as an initial therapy for certain patients newly diagnosed with COPD.

Subjective symptoms and serum methadone concentrations: what should guide dose adjustments in methadone maintenance treatment? A naturalistic cohort study from Norway.

BACKGROUND: There is little evidence-based guidance on how to optimize methadone dosages among patients with opioid addiction undergoing methadone maintenance treatment (MMT). This study aims to investigate whether self-perceived opioid withdrawal symptoms, adverse effects, and self-reported substance use in patients on MMT are related to serum methadone concentrations and the role that these variables could play in clinical decisions on dose adjustments. METHODS: This naturalistic prospective cohort study included clinical and laboratory measurements from 83 patients undergoing MMT in outpatient clinics in Bergen, Norway, from May 2017 to January 2020. Information on age, gender, methadone daily doses and serum concentrations, subjective opioid withdrawal symptoms using 16 items Subjective Opioid Withdrawal Scale (SOWS) questionnaire, self-reported adverse effects, and substance use was obtained. Linear mixed modelling was used for analyzing the data. RESULTS: The mean age of the participants was 45 years, and 33% were women. Almost half reported mild to moderate subjective opioid withdrawal symptoms, and all had experienced at least one subjective adverse effect. The use of at least one substance was reported by 88% of the participants. Serum concentration-to-dose ratios were lower among those who had reported subjective opioid withdrawal symptoms (p) = 0.039). The total SOWS score (p < 0.001); the specific subjective withdrawal symptoms of anxiety (p = 0.004), bone and muscle aches (p = 0.003), restlessness (p = 0.017), and (slightly) shaking (p = 0.046), also use of heroin (p = 0.015) and alcohol (p = 0.011) were associated with lower methadone concentrations. Cannabis use was slightly related to higher methadone concentrations (p = 0.049). CONCLUSIONS: The findings suggest that the patient's self-perceived symptoms and current clinical condition are related to the serum concentrations of methadone. This interpretation supports dose adjustments based on patient-reported symptoms. In some aberrant cases, measurement of serum concentrations together with other individual assessments may be considered to support the clinical decision.

A Prospective Study on Metronomic Scheduling of Non-chemotherapeutic Drugs in Advanced Epithelial Ovarian Cancers.

The objectives of this study are to assess the role of non-chemotherapeutic combination of drugs as maintenance therapy, after standard treatment, for advanced epithelial ovarian cancers (EOC) and to determine the recurrence-free survival (RFS) and cancer-specific survival (CSS). One hundred women with advanced high-grade EOC who had completed standard treatment by primary/interval debulking surgery followed by adjuvant chemotherapy were randomised to either receive (study group) or not to receive (control group) the non-chemotherapeutic maintenance therapy (oral metformin, anastrozole, aspirin, atorvastatin, vitamin D, injection zoledronic acid). Both groups were followed up, and trends of RFS and CSS were analysed. One hundred patients were analysed. Median RFS was 18 months (95% CI: 13-24) in study group versus 16 (95% CI: 14-20) in the control group (P value = 0.57). Median CSS in the study group was lesser than that in the control group (47 months (95% CI: 31-68) versus 51 (95% CI: 32-66), P value = 0.76). Five-year CSS was not significantly different between the groups (47% study vs 40% control, P value = 0.51). The use of combination of non-chemotherapeutic drugs as maintenance therapy was found to have no significant impact on the survival or reduction of recurrences in patients with advanced epithelial ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-020-01261-w.

Cannabis Use and Nonfatal Opioid Overdose among Patients Enrolled in Methadone Maintenance Treatment.

BACKGROUND: Some ecological studies found lower rates of opioid overdose in states with liberalized cannabis legislation, but results are mixed, and the association has not been analyzed in individuals. We quantified the association between cannabis use and nonfatal opioid overdose among individuals enrolled in methadone maintenance treatment (MMT) for opioid use disorder (OUD). METHODS: We recruited a convenience sample of individuals enrolled in four MMT clinics in Washington State and southern New England who completed a one-time survey.Descriptive statistics and multivariate logistic regression compared the prevalence and risk of nonfatal opioid overdose in the past 12 months between participants reporting frequent (at least weekly) or infrequent (once or none) cannabis use in the past month. RESULTS: Of 446 participants, 35% (n = 156) reported frequent cannabis use and 7% (n = 32) reported nonfatal opioid overdose in the past year. The prevalence of nonfatal opioid overdose was 3% among reporters of frequent cannabis use, and 9% among reporters of infrequent/no use (p = 0.02). After imputing missing data and controlling for demographic and clinical factors, the likelihood of self-reported nonfatal opioid overdose in the past year was 71% lower among reporters of frequent cannabis use in the past month (adjusted RR = 0.29, 95% CI 0.10-0.80, p = 0.02). CONCLUSIONS: Among individuals enrolled in MMT, frequent cannabis use in the past month was associated with fewer self-reported nonfatal opioid overdoses in the past year. Methodological limitations caution against causal interpretation of this relationship. Additional studies are needed to understand the prospective impact of co-occurring cannabis on opioid-related outcomes.

The effect of crocin (the main active saffron constituent) on the cognitive functions, craving, and withdrawal syndrome in opioid patients under methadone maintenance treatment.

Individuals under methadone maintenance treatment (MMT) programs are susceptible to several complications, including withdrawal syndrome, craving, and cognitive deficits. This study was designed to elevate the effect of crocin administration on withdrawal syndrome, craving, and cognitive function in subjects under MMT programs. It was a clinical trial that was conducted among 60 patients referred to Soltan Mirahmad Clinic for addict patients in Kashan, Iran. The patients were allocated to two groups including placebo and intervention groups. The intervention group received 30 mg/day crocin (n = 30) and placebo (n = 30) once a day, in 12 weeks. Withdrawal syndrome, craving, and cognitive function parameters were measured before and after the intervention in subjects under MMT programs. Compared with the placebo group, crocin resulted in a significant improvement in craving score (p = .03), and withdrawal symptoms score (p = .01) in the intervention group. In addition, crocin supplementation did not affect cognitive function parameters (e.g., TMT, FAS test, and DGSP score). Overall, crocin supplementation for 12 weeks to patients under MMT programs had beneficial effects on craving and withdrawal symptoms score, but did not affect the cognitive function parameters.

"That's No Longer Tolerated": Policing Patients' Use of Non-opioid Substances in Methadone Maintenance Treatment.

The current overdose crisis in the United States emphasizes the importance of providing substance use treatment programs that are not only effective but tailored to meet the specific needs of the populations they serve. While Methadone Maintenance Treatment (MMT) is considered to be among the best strategies for reducing rates of opioid-involved overdose, its ability to attract and maintain patients may be hindered by a recent focus on policing the non-opioid substance use of people on the program. This paper uses interview data from treatment providers to examine how clinicians conceptualize and organize MMT in regards to patients' use of non-opioid drugs. Responses demonstrate that some treatment providers are increasingly monitoring their patients' use of non-opioid substances and punishing them for infractions, up to and including discharge from treatment. This approach will likely result in increasing rates of patient dropout and a lack of new admissions among people who use non-opioid substances. This article argues that including non-opioid substances in MMT's mandate restricts its ability to improve public health, including by preventing overdoses, and recommends instead that MMT adopt a more individualized approach, shaped by the needs and goals of the patient rather than those of the clinician.

Clinical Effect of Changyanqing Mixture Combined with Mesalazine Enteric-coated Tablets for Maintenance Treatment of Ulcerative Colitis in Remission Period / 中国实验方剂学杂志

Objective:This study aims to evaluate the clinical effect of Changyanqing mixture combined with mesalazine enteric-coated tablets in the maintenance treatment of ulcerative colitis（UC） in remission period. Method:The 140 patients with UC in remission period were randomly divided into control group （70 cases） and observation group （70 cases）. The 61 patients in control group completed the therapy （6 cases lost or lost to follow-up and 3 were eliminated）， 63 patients in observation group completed the therapy （5 cases lost or lost to follow-up and 2 were eliminated）. Both groups′ patients got treatment of lifestyle adjustment， and they also took mesalazine enteric-coated tablets orally， 0.5 g/time， 3 times/day. Patients in observation group took Changyanqing mixture orally for a month in the morning and evening every day， 150 mL/time， and then changed to 150 mL/time， 1 time/day， for 3 consecutive months， finally changed to once every other day for 8 months. Patients in control group took simulated medicine of Changyanqing mixture orally in the same way as observation group. The treatment was continued for 12 months. When UC recurred during the treatment， patients took mesalazine enteric-coated tablets orally at 1 g/time， 3 times/day until remission， when the above intervention plan was continued to be adopted. The recurrence rate， first recurrence time within 12 months （duration from remission to Mayo≥3） and the degree of disease activity at recurrence were recorded. Scores of traditional Chinese medicine（TCM）syndrome and inflammatory bowel disease questionnaire （IBDQ） were evaluated once every 2 months. Before treatment， and at the 6^th and 12^th month after treatment， colonoscopy and mucosal histology were performed once， enteroscopic mucosal scores， Geboes index of mucosal histology were evaluated， and fecal calprotectin（FC） levels were detected. Also， safety evaluation was conducted. Result:During 12 months， the recurrence rate in observation group was 20.63% （13/63）， lower than 39.34% （24/61） in control group（<italic>P</italic><0.05）， the frequency of recurrence and the first recurrence duration in observation group were all less than those in control group（<italic>P</italic><0.01）. All these meant the disease activity of patients in observation group was lighter than that in control group （<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:msup><mml:mrow><mml:mi>χ</mml:mi></mml:mrow><mml:mrow><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:msup></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/444CE72A-DE9D-4013-BB0B-F487F60C8DC8-M003.jpg"><?fx-imagestate width="3.30200005" height="3.64066648"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/444CE72A-DE9D-4013-BB0B-F487F60C8DC8-M003c.jpg"><?fx-imagestate width="3.30200005" height="3.64066648"?></graphic></alternatives></inline-formula>=5.947， <italic>P</italic><0.05）. After repeated measurements of variance analysis， scores of TCM syndrome， enteroscopic mucosal scores， Geboes index and FC levels in two groups gradually increased（<italic>P</italic><0.05）， and scores of IBDQ gradually decreased （<italic>P</italic><0.05） during the 12-month period. At the second， fourth， sixth， eighth， tenth and twelfth month， scores of TCM syndromes in observation group were lower than those in control group （<italic>P</italic><0.01）， and scores of IBDQ were higher than those in control group （<italic>P</italic><0.01）. At the sixth and twelfth month after treatment， intestinal endoscopic mucosal scores， Geboes index and FC levels in observation group were all lower than those in control group （<italic>P</italic><0.01）. And there were no adverse reactions related to Changyanqing mixture. Conclusion:Changyanqing mixture combined with mesalazine enteric-coated tablets in the maintenance treatment of patients with UC in remission can control the FC level， further reduce the recurrence rate， delay the recrudescence-time， reduce the frequency of UC and the disease activity， maintain the good remission state of UC， stabilize the quality of life of patients， and ensure the safety of clinical use.

The JPJDF has Synergistic Effect with Fluoropyrimidine in the Maintenance Therapy for Metastatic Colorectal Cancer.

BACKGROUND: Maintenance chemotherapeutic regimen with low toxicity is needed for metastatic colorectal cancer. A recent patent has been issued on the spleen-strengthening and detoxification prescription (JPJDF), a traditional Chinese herbal medicinal formula with anti-angiogenesis effect. The clinical effect of JPJDF on the maintenance treatment of advanced colorectal cancer has not been evaluated. OBJECTIVE: This study aims to evaluate the effectiveness and safety of JPJDF in combination with fluoropyrimidine compared to fluoropyrimidine alone as maintenance therapy for metastatic colorectal cancer. METHODS: We applied a prospective, randomized, double-blinded, single center clinical study design. A total of 137 patients with advanced colorectal cancer were recruited. Patients received either Fluoropyrimidine (Flu-treated group, n = 68), or Fluoropyrimidine plus JPJDF (Flu-F-treated group, n = 69) as maintenance treatment after 6-cycle of FOLFOX4 or FOLFORI induction treatment. The primary endpoints were Progression-Free Survival (PFS) and Overall Survival (OS). The secondary endpoints were safety, Performance Status (PS) score and other symptoms. RESULTS: The endpoint of disease progression was observed in 91.7% of patients. The PFS was 5.0 months and 3.0 months in the Flu-F-treated and Flu-treated groups, respectively. The OS was 15.0 months and 9.0 months in the Flu-F-treated and Flu-treated groups, respectively. Some common symptoms, such as hypodynamia, anepithymia, dizziness and tinnitus and shortness of breath, were improved in the Flu-F-treated group. There was no significant difference in the common adverse reactions between the two groups. CONCLUSION: JPJDF and fluoropyrimidine have synergistic effect in the maintenance treatment of mCRC.