Systematic Review on Mortality in the Elderly on Methadone Maintenance Treatment.

Opioid dependence is a serious public health concern, particularly for older individuals who have a high prevalence of comorbid conditions. To effectively manage opioid use disorder (OUD), methadone maintenance treatment (MMT) is crucial; however, the MMT poses certain challenges for the aging population. The purpose of this review is to evaluate the impact of MMT on health outcomes, identify predictive factors for mortality, and assess mortality rates among older individuals receiving MMT. A systematic search was performed across databases, including PubMed, Scopus, Web of Science, and Google Scholar, adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies included were published between January 2000 and December 2023, focused on elderly patients (60 years of age and older) receiving MMT and provided information on death rates. A total of 15 studies were examined. The main causes of death for older MMT patients were overdose, respiratory issues, and cardiovascular diseases. The annual mortality rates for these patients ranged from 2% to 10%. Treatment outcomes and mortality were significantly impacted by comorbid conditions. Greater treatment adherence and longer care periods were observed in older individuals, which correlated with better health outcomes and lower mortality. This review makes clear how elderly MMT patients with addiction and chronic health issues require integrated care models. Treatment effectiveness may be further increased by gender-specific interventions. For this aging population, policy reforms and enhanced healthcare support are essential. To enhance clinical results and lower mortality rates among older individuals enrolled in MMT programs, comprehensive age-appropriate care models are crucial. Long-term health outcomes should be investigated further and evidence-based treatments for older individuals with OUD should be developed.

Patient Characteristics From Norway's First Heroin-Assisted Treatment Clinics.

BACKGROUND: Heroin-assisted treatment (HAT) is an evidence-based treatment option for opioid use disorder (OUD), available in a limited number of countries. Norway implemented a 5-year HAT project in 2022, aiming to assess its effectiveness and its potential integration into the country's OUD treatment system. This study describes and compares patients' baseline characteristics from the Oslo and Bergen HAT clinics, providing a comprehensive picture of the unique population and the real-world application of HAT. METHODS: This cross-sectional study examines the baseline characteristics of consenting HAT patients within the first 2 years of operation (n = 86). Self-reported questionnaires gathered sociodemographics, previous treatment experiences, self-reported crime, and substance use, as well as motivations and expectations for treatment. Comparisons between the clinics were carried out using t-tests, Mann-Whitney U tests, Chi-square, and Fisher's exact test. RESULTS: The majority of the patients were enrolled at the Oslo clinic (76%) and were male (80%). At admission, the average age was 45.9, with a significantly younger group in Bergen (42.5 vs 47.3, P < .05). While no patients reported being unhoused, 17% noted unstable housing within the preceding month. Unemployment was prevalent (91%) alongside previous treatment experiences (95%), with a median of 2 prior medication types. In the 3 months preceding HAT initiation, 78% of patients reported being victims of crime, and 44% committed at least one crime. Over their lifetime, 2 in 5 participants (41%) had experienced an unwanted overdose and 43% had shared syringes and equipment. CONCLUSION: This study reveals a cohort experiencing societal marginalization, including unstable housing, unsatisfactory prior OUD treatment, high-risk behaviors, and frequent interactions with criminal activities, predominantly as victims. While the Oslo and Bergen clinics serve a similar patient profile, notable differences emerged in the reasons for discontinuing past OUD treatment and crime-related factors.

Decitabine-based treatment strategy improved the outcome of HSCT in JMML: a retrospective cohort study.

Introduction: Pre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenile myelomonocytic leukemia (JMML) patients. Methods: This retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DAC monotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival. Results: There were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups (p=0.769). Clinical remission rates significantly improved following bridging treatment (p=0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p=0.002). Conclusion: Implementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments.

Meta-analysis of effectiveness and safety of proteasome inhibitor-dependent maintenance treatment for multiple myeloma a systematic review.

Background: Even with significant advancements, treating multiple myeloma (MM) remains difficult. At present, the main treatment methods include combined treatment of stem cell transplantation, drug treatment, etc. With the clarification of the molecular biological mechanism of MM, as well as the in-depth study of the internal signal of myeloma cells and the microenvironment of MM patients, more and more new drugs targeting myeloma and microenvironment are gradually used in clinical maintenance treatment, such as inhibit the proteosome: ixazomib, bortezomib and carfilzomib, immune - modulators: thalidomide and lenalidomide, monoclonal antibodies, etc. have made great progress in MM maintenance treatment. With the continuous development of proteasome inhibitor maintenance treatment in MM, the prognosis of the disease has been significantly improved. Our aim is to evaluate the effectiveness and adverse reactions of proteasome inhibitors in maintenance therapy for multiple myeloma, providing new ideas for clinical medication. Methods: Four databases containing randomized controlled studies on the effectiveness and safety of proteasome inhibitors in the maintenance therapy of multiple myeloma are retrieved by the computer. Once the quality of the literature has been thoroughly evaluated, run the data via the RevMan 5.3 software. Results: Eventually 8 studies were added in this systematic review. Compared with the placebo group, proteasome inhibitor in maintenance treatment of multiple myeloma patients with prolonged the survival without progression and overall existence. 5 studies reported the peripheral neuropathy of multiple myeloma in the treatment group compared to placebo group, which was remarkably greater (OR: 1.98; 95 % Cl: 1.35, 2.92; P < 0.001) compared to placebo group, Serious adverse events (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01), Rash (OR: 2.23; 95 % Cl: 1.62, 3.05; P < 0.001) and Vomiting (OR: 5.12; 95 % Cl: 3.36, 7.80; P < 0.001). The Serious adverse events of the treatment group were remarkably greater compared with the untreated group (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01). Conclusion: The study results proposed that proteasome inhibitors are effective in the multiple myeloma maintenance treatment compared with the placebo group. Bortezomib has certain advantages in prolonging PFS, followed by ixazomib and carfilzomib in terms of efficacy. Bortezombib may be superior to carfilzombib in extending OS. However, the adverse reactions caused by proteasome inhibitors, such as Peripheral neuropathy, Serious adverse events, Rash, Vomiting, etc., should be paid enough attention.

Exploring real-world prescribing patterns for maintenance treatment in bipolar disorders: a focus on antidepressants and benzodiazepines.

OBJECTIVE: Bipolar disorders (BD) are characterized by highly recurrent nature, necessitating adequate maintenance treatment for long-term disorder control. This study aimed to investigate real-world prescribing patterns among outpatients with BD, focusing on the utilisation of antidepressants (AD) and benzodiazepines (BDZ). METHODS: We analysed prescription patterns of the five main groups of psychotropic medications (antipsychotics, mood stabilizers, AD, BDZ, and anticholinergic medications) and their relationships with basic socio-demographic and clinical data in a sample of 107 clinically stable BD outpatients (75.7% female, age 44.8 ± 11.7). RESULTS: Maintenance therapy predominantly involved polypharmacy (92.5%), with mood stabilizers (87.9%) and antipsychotics (80.4%, predominantly second-generation) being the most commonly prescribed. Our findings highlight a high percentage of patients prescribed AD (50.5%) and BDZ (54.2%). BDZ patients, compared to the non-BDZ group in maintenance treatment, were significantly older with longer psychiatric history and a decreased likelihood of comorbid personality disorder diagnoses. CONCLUSIONS: This study offers insights into prescribing practices within a university psychiatric clinic in the Western Balkans. The prevalent use of polypharmacy in real-world clinical settings, along with high percentage of patients prescribed AD and BDZ, suggests a gap between guideline recommendations and clinical practice, indicating a lack of consensus or standardized approaches in clinical practice.

Study uncovers prescribing practices in a Western Balkans university psychiatric clinic, revealing high polypharmacy prevalence (92.5%) among clinically stable bipolar disorder (BD) outpatients.Most BD outpatients received mood stabilizers, particularly lamotrigine, and second-generation antipsychotics, notably olanzapine, with a minority on monotherapy.Antidepressant and benzodiazepine usage was notably high despite guidelines favouring monotherapy, reflecting challenges in managing residual morbidity.AD usage in BD type I is discouraged due to risks, while their use in BD type II is considered in certain scenarios, emphasising tailored treatment.High mean daily BDZ dose (approximately 3.5mg lorazepam equivalents) in non-acute outpatient BD maintenance therapy raises concerns about potential long-term implications for patient health and underscores the need for vigilant monitoring of prescribing practices.

Clinical efficacy and future application of indigo naturalis in the treatment of ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by non-specific inflammation. Managing UC presents significant challenges due to its chronic nature and high recurrence rates. Indigo naturalis has emerged as a potential therapeutic agent in clinical UC treatment, demonstrating advantages in alleviating refractory UC and maintaining remission periods compared to other therapeutic approaches. AIM OF REVIEW: This review aims to elucidate the potential mechanisms underlying the therapeutic effects of indigo naturalis in UC treatment, assess its clinical efficacy, advantages, and limitations, and provide insights into methods and strategies for utilizing indigo naturalis in UC management. MATERIALS AND METHODS: Comprehensive data on indigo naturalis were collected from reputable online databases including PubMed, GreenMedical, Web of Science, Google Scholar, China National Knowledge Infrastructure Database, and National Intellectual Property Administration. RESULTS: Clinical studies have demonstrated that indigo naturalis, either alone or in combination with other drugs, yields favorable outcomes in UC treatment. Its mechanisms of action involve modulation of the AHR receptor, anti-inflammatory properties, regulation of intestinal flora, restoration of the intestinal barrier, and modulation of immunity. Despite its efficacy in managing refractory UC and prolonging remission periods, indigo naturalis treatment is associated with adverse reactions, quality variations, and inadequate pharmacokinetic investigations. CONCLUSION: The therapeutic effects of indigo naturalis in UC treatment are closely linked to its ability to regulate the AHR receptor, exert anti-inflammatory effects, mcodulate intestinal flora, restore the intestinal barrier, and regulate immunity. Addressing the current shortcomings, including adverse reactions, quality control issues, and insufficient pharmacokinetic data, is crucial for optimizing the clinical utility of indigo naturalis in UC management. By refining patient-centered treatment strategies, indigo naturalis holds promise for broader application in UC treatment, thereby alleviating the suffering of UC patients.

Health service utilization, substance use treatment response, and death in patients with opioid use disorder and comorbid hepatitis C findings from prospective cohort study with administrative database linkage.

BACKGROUND: Among patients with opioid use disorder (OUD), high rates of overdose and death have been reported in subgroups with Hepatitis C Virus (HCV). Evidence on the comorbid effect of HCV on clinical and substance use trajectories has been limited by small sample sizes, short follow-up, and heavy reliance on administrative data which lacks granularity on important prognostic factors. Additionally, few studies include populations on substance use treatment. AIM: To establish the impact of HCV exposure (antibody positivity) on health care utilization patterns, substance use treatment response, and death in a cohort of patients with OUD on opioid agonist therapy (OAT). METHODS: This multi-center prospective cohort study recruited adult patients with OUD on OAT from 57 substance use treatment centers in Ontario, Canada. The study collected substance use outcomes, and classified patients with ≥50 % positive opioid urine screens over one year of follow-up as having poor treatment response. Additional data obtained via linkage with ICES administrative databases evaluated the relationship between HCV status, healthcare service utilization, and death over 3 years of follow-up. Multiple logistic regression models established the adjusted impact of HCV on various outcomes. RESULTS: Among recruited participants (n = 3430), 44.10 % were female with a mean age of 38.64 years (Standard deviation: 10.96). HCV was prevalent in 10.6 % of the cohort (n = 365). Methadone was used most often (83.9 %, n = 2876), followed by sublingual buprenorphine (16.2 %, n = 554). Over the three-year follow-up, 5.3 % of patients died (n = 181). Unadjusted results reveal rates of hospitalization (all-cause, mental-health related, critical care) and emergency department visits (mental health-related), were significantly higher among HCV patients. Associations diminished in adjusted models. Active injection drug use exhibited the highest predictive risk for all outcomes. CONCLUSION: A high degree of acute physical and mental illness and its resulting health service utilization burden is concentrated among patients with OUD and comorbid HCV. Future research should explore the role for targeted interventions and how best to implement integrated healthcare models to better address the complex health needs of HCV populations who inject drugs.

[A multicenter retrospective study discussion on maintenance treatment strategies for mantle cell lymphoma].

Objective: This study aims to explore the survival advantages of different maintenance strategies for MCL. Methods: Clinical data of 693 newly diagnosed MCL patients in multi-centers admitted from April 1999 to December 2019 were collected. 309 cases received maintenance treatment. The characteristics of patients in different maintenance treatment groups were summarized and Kaplan-Meier survival and prognosis analysis were conducted. Results: The overall 3-year and 5-year progression-free survival (PFS) rates were (73.5±2.9) % and (53.6±4.3) %, respectively. The 3-year and 5-year overall survival (OS) rates were (94.2±1.5) % and (82.7±3.2) %, respectively. The clinical features of different maintenance treatment groups were generally consistent. The 3-year PFS rates of rituximab maintenance, lenalidomide maintenance, BTK inhibitor maintenance and dual-drug maintenance were (70.4±4.1) %, (69.1±7.6) %, (86.9±5.0) %, and (80.4±5.1) %, respectively. Corresponding 3-year OS rates were (92.9±2.4) %, (97.3±2.7) %, (97.9±2.1) %, and (95.3±2.7) %, respectively. There were no significant difference in different groups (P=0.632, 0.313). Survival analysis identified the MCL International Prognostic Index (MIPI) high-risk group and achieving complete remission before maintenance treatment as independent risk factors for PFS. The MIPI high-risk group, high-dose cytarabine application, treatment lines, and early disease progression (POD24) emerged as independent risk factors for OS. Conclusion: Comparing the different maintenance strategies of MCL, the result showed that BTK inhibitors (BTKi) maintenance demonstrated preliminary advantages in survival. Meanwhile, high-risk group according to MIPI and incomplete remission before maintenance treatment were significant factors related to disease progression.

Maintenance treatment with oral anticancer agents after first-line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Maintenance therapy following first-line chemotherapy is of particular significance in patients diagnosed with recurrent or metastatic nasopharyngeal carcinoma (NPC). We conducted a meta-analysis to investigate the impact of maintenance therapy (MT) on the survival prognosis of individuals with recurrent or metastatic NPC. METHODS: The databases Embase, PubMed, and the Cochrane Library were thoroughly searched in a comprehensive manner. Prospective studies of MT for recurrent or metastatic NPC are required. Study endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS: Two randomized controlled clinical trials, with a total of 294 participants, were analyzed. The maintenance therapy group consisted of 140 participants, while the remaining participants were in the non-maintenance therapy (non-MT) group. The MT group showed a notable enhancement in PFS compared to the non-MT group, with a hazard ratio(HR) of 0.44 and a 95% Confidence interval [CI] of 0.34-0.58 (p < 0.0001). Overall survival was also significantly improved (HR0.42, 95% CI 0.30-0.58; p < 0.0001). The incidence of grade 3 or 4 side effects in the MT group was leukopenia (2.9%), thrombocytopenia (0.7%), and anemia (4.3%), hand-foot syndrome (5.8%), and thrombocytopenia (0.7%). oral mucositis (1.5%), and nausea and vomiting (2.2%). CONCLUSIONS: Maintenance therapy with S-1 (tegafur/gimeracil/oltiracetam) or capecitabine following first-line chemotherapy significantly enhanced OS and PFS in patients with recurrent or metastatic nasopharyngeal carcinoma, while exhibiting minimal incidence of grade 3-4 side effects.

Methadone treatment utilization and overdose trends among Medicaid beneficiaries in New Jersey before and during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic disrupted the traditional mode of methadone maintenance treatment (MMT) delivery through the imposition of lockdowns and social distancing measures. In response, policy makers granted flexibilities to providers delivering MMT to change their practices to maintain patient participation while accommodating the measures imposed to prevent the spread of COVID-19. This study examines the utilization of MMT and overdoses of patients receiving MMT during the COVID-19 pandemic in one mid-Atlantic state. MATERIALS AND METHODS: We analyzed Medicaid claims data for 2018-2020, calculating weekly trends for starts, discontinuations, and medically-treated overdoses for beneficiaries receiving MMT who had been continuously enrolled in Medicaid for the previous 12 months, to account for changes in the composition of the Medicaid population following the COVID-19 public health emergency (PHE). We completed data analyses from January to June 2022. RESULTS: We observed countervailing trends in new starts, which experienced an immediate, non-significant dip of -22.47 per 100,000 Medicaid beneficiaries (95%CI, -50.99 to 6.04) at the outset of the pandemic followed by an increasing upward trend of 1.41 per 100,000 beneficiaries per week (95%CI, 0.37 to 2.46), and in discontinuations, which also experienced an immediate dip of -3.23 per 1000 MMT enrollees (95%CI, -4.49 to -1.97) followed by an increasing upward trend of 0.14 per 1000 MMT enrollees per week (95%CI, 0.09 to 0.19). The net result of these shifts was a stable, slowly increasing rate of MMT treatment of 0.02 % per week before and after the PHE. We also found no statistically significant association of the PHE with medically-treated overdoses among beneficiaries enrolled in MMT (trend change = 0.02 overdoses per 10,000 MMT enrollees, 95%CI, -0.05 to 0.09). CONCLUSIONS: New Jersey achieved overall stability in MMT treatment prevalence following the pandemic's onset, while some changes in treatment dynamics took place. This outcome may reflect that the extensive flexibilities granted to providers of MMT by the state and federal government successfully maintained access to MMT for Medicaid beneficiaries through the pandemic without increasing risk of medically-treated overdose. These findings should inform policy makers developing the post-COVID-19 legal and regulatory landscape.

Effectiveness and safety of low dose Rituximab as remission-maintenance treatment for patients with refractory idiopathic inflammatory myopathies: results of a retrospective study from a monocentric cohort.

OBJECTIVE: Our aim was to assess efficacy and safety of Rituximab (RTX) in patients with refractory Idiopathic inflammatory myopathies (IIM) from a monocentric cohort. Thereafter, we evaluated the efficacy of a low-dose RTX regimen as a remission-maintenance therapy. METHODS: We retrospectively evaluated a cohort of patients affected with IIM treated with RTX. All patients were refractory to glucocorticoids (GC) and at least one immunosuppressant. Two infusions of 1 g two weeks apart were considered as standard cycle of RTX, a single dose of 1 g every six months was deemed as a low-dose RTX regimen. Complete and partial response were defined according to physician's judgment, laboratory and radiological features. RESULTS: Thirty-six patients affected with IIM were enrolled. Eighteen patients (50%) required the use of RTX for muscular involvement, 6 (16.7%) for interstitial lung disease (ILD), 12 (33.3%) for both myositis and ILD. We observed complete response to RTX in 25 patients (69.4%), partial response in 7 (19.4%) and no response in 4 (11.1%), with an overall response of 88.8% (partial and complete response). From the subgroup of twenty-five patients that achieved a complete response, six were treated with a low dose maintenance therapy maintaining a complete response to RTX. Twenty-six patients who achieved a complete or partial response were able to decrease the mean daily GC dose. Infections were the major adverse events detected in our study. CONCLUSIONS: RTX shows favorable outcomes in refractory patients with IIM. A low-dose regimen of RTX appears to be effective in maintaining remission after induction with standard dose. Key Points • The precise pathogenic mechanism of idiopathic inflammatory myopathies (IIM) remains elusive; however, a growing body of data support the autoimmune hypothesis. In this context, rituximab, a B cell-depleting agent, has emerged as a second-line therapeutic option in IIM. • Several studies have assessed It its effectiveness in refractory IIM patients. • Limited information exists on the use of Rituximab as maintenance therapy in patients who have achieved remission following induction therapy with Rituximab.

Cerebral blood flow in the paracentral lobule is associated with poor subjective sleep quality among patients with a history of methadone maintenance treatment.

Introduction: Sleep disorders are prevalent and significant among individuals receiving methadone maintenance treatment (MMT), adversely affecting their quality of life and treatment adherence. While cerebral blood flow (CBF) plays a crucial role in the development of various diseases, its relationship with sleep disorders remains uncertain. This observational study focuses on possible correlations between CBF and poor subjective sleep quality in MMT patients. Methods: A total of 75 participants with a history of MMT were recruited and assessed using pseudo-continuous arterial spin labeling magnetic resonance imaging to determine CBF. A LAASO regression model was employed to identify the region of interest (ROI) most associated with sleep disturbance. The association between the CBF of the ROI and the Pittsburgh Sleep Quality Index (PSQI) was examined using regression analyses. Age, gender, BMI, history of hypertension, diabetes, hyperlipidemia, and methadone withdrawal were included as covariates. Results: Among MMT patients with poor subjective sleep quality, significantly higher CBF was observed in the right paracentral lobule (56.1057 ± 11.1624 ml/100 g/min, p = 0.044), right cerebelum_3 (56.6723 ± 15.3139 ml/100 g/min, p = 0.026), right caudate nucleus (48.9168 ± 6.9910 ml/100 g/min, p = 0.009), and left caudate nucleus (47.6207 ± 6.1374 ml/100 g/min, p = 0.006). Furthermore, a positive correlation was found between CBF in the right paracentral lobule and the total PSQI score (ß = 0.1135, p = 0.0323), with the association remaining significant even after adjustment for covariates (ß = 0.1276, p = 0.0405). Conclusion: MMT patients with poor subjective sleep quality exhibited significantly altered CBF in multiple brain regions. The association between increased CBF in the right paracentral lobule and subjective sleep quality in MMT patients could be crucial in understanding sleep disorders in individuals undergoing MMT. Clinical trial registration: https://www.chictr.org.cn/, identifier: ChiCTR2100051931.

A network meta-analysis of efficacy and safety for first-line and maintenance therapies in patients with unresectable colorectal liver metastases.

Background: Evidence comparing the efficacy of different treatments for patients with unresectable colorectal liver metastases (CRLM) receiving first-line or maintenance therapy is sparse. We aimed to assess the efficacy and safety of these treatments, with a distinct focus on evaluating first-line and maintenance treatments separately. Methods: We conducted Bayesian network meta-analyses, sourcing English-language randomized controlled trials (RCTs) published through July 2023 from databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and key conference proceedings. Phase Ⅱ or Ⅲ trials that assessed two or more therapeutic regimens were included. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), adverse events graded as 3 or above (SAE), and R0 liver resection rate. Hazards Ratios (HRs) and 95% confidence intervals (CI) were used as effect size for OS and PFS, Odds Ratios (ORs) and 95% CI were used for ORR, SAEs and R0 resection rate. Subgroup and sensitive analyses were conducted to analysis the model uncertainty (PROSPERO: CRD42023420498). Results: 56 RCTs were included (50 for first-line treatment, six for maintenance therapies), with a total of 21,323 patients. Regarding first-line, for OS, the top three mechanisms were: local treatment + single-drug chemotherapy (SingleCT), Targeted therapy (TAR)+SingleCT, and TAR + multi-drug chemotherapy (MultiCT). Resection or ablation (R/A)+SingleCT, S1, and Cetuximab + intensified fluorouracil-based combination chemotherapy (ICTFU) were identified as the best treatments. For PFS, the top three mechanisms were: Immune therapy + TAR + MultiCT, multi-targeted therapy (MultiTAR), TAR + SingleCT. The top three treatments were: Atezolizumab + Bevacizumab + fluorouracil-based combination chemotherapy (CTFU), TAS-102+bevacizumab, Bevacizumab + ICTFU. Cetuximab + CTFU was the best choice for RAS/RAF wild-type patients. Regarding maintenance treatment, Bevacizumab + SingleCT and Adavosertib were the best options for OS and PFS, respectively. For safety, MultiCT was the safest, followed by local treatment + MultiCT, TAR + MultiCT caused the most SAEs. Bevacizumab plus chemotherapy was found to be the safest among all targeted combination therapies. Conclusion: In first-line, local treatment or targeted therapsy plus chemotherapy are the best mechanisms. R/A + SingleCT or CTFU performed the best for OS, Atezolizumab + Bevacizumab + ICTFU was the best option regarding PFS. For RAS/RAF wild-type patients, Cetuximab + CTFU was the optimal option. Monotherapy may be preferred choice for maintenance treatment. Combination therapy resulted in more SAEs when compared to standard chemotherapy.

Treatment non-adherence among methadone maintenance patients and associated factors: a multicenter, cross-sectional study in Vietnam.

OBJECTIVE: This multicenter, cross-sectional study was conducted to investigate the prevalence of treatment non-adherence and its associated factors among methadone maintenance patients in Vietnam. METHODS: This secondary data analysis was conducted using the data from a previous study. Six hundred patients were interviewed face-to-face to collect data on their demographic characteristics and social support. Information about the treatment characteristics and patients' non-adherence was gathered from medical records and books monitoring their treatment process. Treatment non-adherence was defined as missing at least one methadone dose in the last three months. RESULTS: The overall prevalence of non-adherence was 45.7%. The average social support score of patients who completely adhered to treatment was significantly higher than that of those who did not (p < 0.001). In the multivariate logistic regression model, for each one-unit increase in social support (one score), treatment time (a year), and patient's monthly income (one million Vietnam dongs), the odds of non-adherence decreased by 28% (aOR = 0.72, 95%CI 0.59-0.88, p = 0.002), 15% (aOR = 0.85, 95%CI 0.80-0.91, p < 0.001) and 9% (aOR = 0.91, 95%CI 0.85-0.97, p = 0.004), respectively. Patients living in Son La (a mountainous province) were 1.72 times (95%CI 1.09-2.71) more likely to be non-adherent as compared to those in other areas (p = 0.020). As per univariate analyses, other associated factors could be age, education level, family monthly income, occupation, and opioid relapse (p < 0.001). CONCLUSIONS: A high non-adherence rate was found among Vietnamese methadone maintenance patients. Interventions involving social support, occupation, income, and education are needed to improve their treatment adherence.

Predictors of retention in heroin-assisted treatment in Denmark 2010-2018 - A record-linkage study.

INTRODUCTION: While randomized-controlled trials have shown that heroin-assisted treatment (HAT) is superior to methadone maintenance alone in treatment of refractory clients, little is known about client factors associated with retention in HAT in routine care. METHODS: This retrospective cohort study assessed predictors of retention in first treatment episode among a consecutive cohort of clients admitted to HAT in Denmark from 2010 to 2018, who could be matched to the Danish population register and for whom a Short Form Health Survey (SF-36) was available at admission (N = 432). The study derived predictors from client self-reports at intake and administrative data available in national registers. Cox proportional hazards regression modelled retention in treatment. RESULTS: The one-year retention rate was 69.63 % (95 % CI 65.06 %-73.74 %), and the median time in treatment was 2.45 years (95 % CI, 1.83-3.12). Bivariate analyses showed that retention was lower for clients who had recent cocaine or benzodiazepine use and among those who had experienced an overdose in the year prior to enrollment in HAT. Age below 40, recent illegal activity, poorer emotional wellbeing, previous residential treatment experience, and previous intensive outpatient treatment were also predictors of dropout from HAT. CONCLUSIONS: This observational study found that retention in HAT in routine care was similar to rates observed in randomized-controlled trials conducted in other countries. The results suggest that addressing polysubstance use as part of the HAT program may promote long-term retention, as may directing resources to certain subgroups identified at intake, including clients under 40 years and those who report recent criminal activity, emotional problems, or overdoses. The findings that previous residential treatment and intensive outpatient treatment were associated with dropout were unexpected.

Impact of the Ottawa model on opiate screening and smoking cessation in methadone-treated patients with opioid use disorder: A retrospective cohort analysis.

INTRODUCTION: Approximately 60 million individuals worldwide used opioids in 2021, constituting 1.2% of the global adult population. This study aimed to evaluate the effectiveness of integrated treatment strategies for opioid use disorder and nicotine use disorder by assessing the impact of smoking cessation within a methadone treatment framework. METHODS: In a retrospective cohort study, 53 methadone maintenance patients were divided into 16 treatment-seeking smokers (TSS) and 37 treatment-rejecting smokers (TRS) based on their participation in the Ottawa model for smoking cessation plus 16 weeks of varenicline treatment. Both groups received standard methadone treatment for 68 weeks. TSS were followed up for 44 weeks to assess smoking cessation outcomes, while TRS had none due to their lack of participation in smoking cessation treatment. RESULTS: The median age of the TSS group was 48 years, while that of the TRS group was 45.5 years. Males comprised 75% of TSS and 94.6% of the TRS. TSS exhibited an 83% decrease in positive opioid screen results compared to TRS (p=0.023). In TSS, peak smoking cessation success was observed at week 20, with 57% of participants maintaining carbon monoxide levels <5 ppm. CONCLUSIONS: The significant reduction in positive opioid screens and the high smoking cessation rate in the TSS group highlight the efficacy of combined treatment methods. This study underscores the advantages of integrating smoking cessation with methadone maintenance treatment, indicating that comprehensive approaches can substantially improve treatment outcomes.

Rituximab maintenance treatment outcomes in patients with relapsing neuromyelitis optica spectrum disorder: a monocentric retrospective analysis.

Some patients with neuromyelitis optica spectrum disorder (NMOSD) experience relapse after rituximab (RTX) treatment. In this retrospective study, we analyzed the recurrence-related clinical features, laboratory investigation results, and dosing protocol of 30 female patients with relapsing NMOSD with immunoglobulin G autoantibodies against aquaporin-4 and relapses during repeated 0.5 g RTX infusions as maintenance treatment. The median follow-up period was 6.62 years. Thirty-five episodes were observed, with myelitis being the most frequent. The median expanded disability status scale change score was 0.50. The recurrence rate decreased by 44.23%/year with RTX infusion. Approximately 85.71% of the patients showed relapse without RTX infusion within 10 months. Overall, RTX may be effective for relapsing NMOSD cases.

Avelumab first-line maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma: real-world results from a Korean expanded access program.

Background: The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP). Methods: This open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice. Results: Overall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received >12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died. Conclusion: Results from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies.

Prevalence of high impulsivity and its relation to sleep indices in opioid use disorder patients receiving methadone maintenance treatment.

BACKGROUND: The relation between impulsivity and sleep indices is not well determined in patients receiving methadone maintenance treatment (MMT). AIMS: to evaluate high impulsivity prevalence, its risk factors and relation with sleep indices. METHODS: a random MMT sample (n = 61) plus MMT current cocaine users (n = 20) were assessed for impulsivity (Barratt impulsivity scale [BIS-11] and Balloon Analogue Risk task [BART]), sleep quality (Pittsburg Sleep Quality Index [PSQI]), sleepiness (The Epworth sleepiness scale [ESS]), and substance in urine. RESULTS: 81 patients, aged 56.6 ± 10, 54.3% tested positive to any substance, 53.1% with poor sleep (PSQI>5) and 43.2% with daytime sleepiness (ESS >7) were studied. Impulsivity (BIS-11 ≥ 72) prevalence was 27.9% (of the representative sample), and 30.9% of all participants. These patients characterized with any substance and shorter duration in MMT with no sleep indices or other differences including BART balloon task performance (that was higher only in any substance than non-substance user group). However, impulsive score linearly correlated with daytime sleepiness (R = 0.2, p = 0.05). Impulsivity proportion was lowest among those with no cocaine followed by cocaine use and the highest in those who used cocaine and opiates (20.8%, 33.3% and 60% respectively, p = 0.02), as daily sleep (38.3%, 42.1% and 60%, p = 0.3) although not statistically significant. CONCLUSION: Daytime sleepiness correlated with impulsivity, but cocaine usage is the robust factor. Further follow-up is warranted to determine whether substance discontinuing will lead to a reduction in impulsivity, and improved vigilance. Sleep quality did not relate to daytime sleepiness and impulsivity and need further research.

Confidence in providing methadone maintenance treatment of primary care providers in Vietnam.

BACKGROUND: Delivering methadone treatment in community health facilities by primary care providers is a task-shifting strategy to expand access to drug use treatment, especially in rural mountainous areas. This study aims to investigate factors related to confidence in providing methadone treatment among primary care providers in Vietnam to inform good practice development. METHODS: We conducted a cross-sectional survey with 276 primary care providers who were physicians, physician assistants, nurses, pharmacists or dispensing staff from 67 communes in a mountainous province in Northern Vietnam. Using self-report scales, we measured providers' confidence in providing methadone treatment, beliefs in harm reduction, perceived work-related support, perceived stigma and risk in working with drug-using patients, and empathy towards this population. We used multiple linear regression analyses to explore factors associated with providers' confidence in providing methadone treatment in the whole sample and to compare two groups of providers who did and did not have experience providing methadone. Potential associated factors were measured at facility and provider levels. RESULT: 114 (41.3%) participants had previously experience in providing methadone treatment. Providers with methadone treatment experiences had higher confidence in and more accurate knowledge of methadone treatment, perceived less stigma of working with drug-using patients, and reported more work-related support than those without experiences. Higher medical education is associated with lower confidence in providing methadone treatment among providers without methadone experiences, but higher confidence among providers with methadone experiences. Better methadone knowledge was associated with greater confidence in providing methadone treatment among inexperienced providers but not among those with experiences. Receiving work-related support was associated with greater confidence in providing treatment in both groups, regardless of their past methadone experiences. CONCLUSION: In rural provinces where methadone treatment has been expanded to primary care clinics, interventions to improve primary care providers' confidence should benefit professionals with diverse experiences in providing methadone treatment. Continued training and support at work for providers is essential to ensuring quality in decentralized methadone treatment.