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OBJECTIVES: To investigate the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS), venlafaxine or a combination of both treatments as a maintenance treatment in patients with treatment-resistant depression (TRD). METHODS: In a three-arm open-label study, 66 patients, including 45 remitters, who responded to rTMS (n=25), venlafaxine (n=22), or a combination of both treatments (n=19) continued to receive the treatment that led to a response as a maintenance treatment over 12 months. Maintenance rTMS was administered twice per week for 1 month, once per week for 2 months, and once every 2 weeks for 9 months. Venlafaxine was maintained at the dose that induced a clinical response (150 or 225mg/day). RESULTS: After the 12-month follow-up, the rates of remitters (HDRS<8) were not different between the three groups (χ²=1.25; P=.3). The rates of patients who not relapsed (HDRS<15) were not different between groups (χ²=0.33; P=.8): 40.0% in the rTMS group, 45.1% in the venlafaxine group and 36.9% in the combination group. CONCLUSIONS: The three maintenance approaches exhibited similar efficacies in relapse prevention and the maintenance of remission in patients with TRD. [ABSTRACT FROM AUTHOR]

Objectives: Although clinically highly relevant, the recognition and treatment of bipolar mixed states has played only an underpart in recent guidelines. This WFSBP guideline has been developed to supply a systematic overview of all scientific evidence pertaining to the acute and longterm treatment of bipolar mixed states in adults. Methods: Material used for these guidelines is based on a systematic literature search using various data bases. Their scientific rigour was categorised into six levels of evidence (A-F), and different grades of recommendation to ensure practicability were assigned. We examined data pertaining to the acute treatment of manic and depressive symptoms in bipolar mixed patients, as well as data pertaining to the prevention of mixed recurrences after an index episode of any type, or recurrence of any type after a mixed index episode. Results: Manic symptoms in bipolar mixed states appeared responsive to treatment with several atypical antipsychotics, the best evidence resting with olanzapine. For depressive symptoms, addition of ziprasidone to treatment as usual may be beneficial; however, the evidence base is much more limited than for the treatment of manic symptoms. Besides olanzapine and quetiapine, valproate and lithium should also be considered for recurrence prevention. Limitations: The concept of mixed states changed over time, and recently became much more comprehensive with the release of DSM-5. As a consequence, studies in bipolar mixed patients targeted slightly different bipolar subpopulations. In addition, trial designs in acute and maintenance treatment also advanced in recent years in response to regulatory demands. Conclusions: Current treatment recommendations are still based on limited evidence, and there is a clear demand for confirmative studies adopting the DSM-5 specifier with mixed features concept. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: For the first time to estimate the risk of recurrence among patients with a single manic/mixed episode by systematically reviewing prior studies on cohorts of adults, and cohorts of children and adolescents, respectively. Methods: A systematic literature search up to August 2017 was carried out including studies in which < 25% of the participants were estimated to have had a mood episode that required pharmacological treatment prior to the index manic or mixed episode at inclusion. Results: Three studies including a total of 293 adult patients with a single manic or mixed episode and three studies of children and adolescents including 126 patients were identified. In the adult studies, 31%, 40% and 42% experienced recurrence after recovery within 1 year, 59% after 2 years, and 58% after 4 years, respectively. In the studies on children and adolescents, 40% and 52% experienced recurrence after recovery within 1 year, 30% and 60% after 2 years and 64% and 67% after 4 to 5 years, respectively. Results from meta‐analyses showed a 1‐year rate of recurrence of 35% (95% confidence interval [CI]: 30‐41%) in adults, and in adolescents/children, a 1‐year rate of recurrence of 48% (95% CI: 38‐58%), a 2‐year rate of 46% (95% CI: 33‐60%) and a 4‐5‐year rate of recurrence of 65% (95% CI: 52‐77%; as data from different studies were included at 1, 2 and 5 years, rates of recurrence did not increase steadily with time). Conclusions: The rate of recurrence is high among adults as well as children and adolescents. It is important that clinicians and patients as well as relatives are well informed about these high risks when deciding to start maintenance treatment or not following onset of a single manic or mixed episode. [ABSTRACT FROM AUTHOR]

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients treated with intravenous immunoglobulin (IVIg) usually start with a standard dosage of 2 g/kg bodyweight. Only a minority of patients has a sustained improvement, and most require ongoing maintenance treatment. Preferred IVIg regimens, however, vary considerably between doctors and at present it is unknown which is optimal. As there are also large differences in IVIg dosage and interval requirements between patients, optimal IVIg maintenance treatment of CIDP is even more complex. The lack of evidence-based guidelines on how IVIg maintenance treatment should be administered may potentially lead to under- or overtreatment of this expensive therapy. We provide an overview of published practical IVIg maintenance treatment regimens, IVIg maintenance schedules used in randomized controlled trials and one based upon our own long-term experience on how this treatment could be given in CIDP. [ABSTRACT FROM AUTHOR]

Our goal consisted of describing the 4-year prevalence, contributors, and interventions for long QTc's in methadone maintenance treatment. Cardiologists' diagnosis of long QTc defined case-ness in 62 patients. Long QTc categories, drawn from epidemiological reports, encompassed 440 to 469 (borderline), 470 to 499 (moderate), and 500+ milliseconds (severe). Data collection included electrocardiograms, demographic characteristics, contributors to long QTc, and interventions-plus-outcomes (defined by resolution of long QTc). Of 62 patients, 21 had 39 long QTc episodes-a 4-year case prevalence of 34%, and an annual episode incidence of 15.7 per 100. Contributing factors identified in 36 of 39 episodes consisted of medication management (n = 19), illicit drug use (n = 11), and other factors (n = 6). Long QTc reverted to normal in 38 of 39 episodes. Of 21 patients, 12 (57%) experienced one or two recurrences. Methadone maintenance treatment physicians normalized most episodes as outpatients, often in collaboration with patients' primary care physicians. One fifth of episodes required hospitalization and other specialty care. Lack of timely QTc normalization may have accounted for one sudden death. [ABSTRACT FROM AUTHOR]

Background/Objectives Accumulating evidence has shown that omalizumab is an effective and safe treatment for chronic spontaneous urticaria (CSU), but there is little information regarding the use of omalizumab to treat CSU in Taiwan. Reports on clinical experiences with using omalizumab for CSU for more than 6 months are also lacking. Methods A retrospective review of medical records of consecutive CSU patients receiving omalizumab treatment in the Urticaria Special Clinic of one tertiary referral center in Taiwan was conducted. We analyzed clinical features of the patients, treatment efficacy and safety, and also long-term outcomes after omalizumab treatment. An Urticaria Activity Score over 7 days (UAS7) was recorded at each visit. Results A total of 17 CSU patients were identified (11 females and 6 males, age range: 21–83 years) with a baseline mean UAS7 of 29.8 ± 8.9 despite antihistamine treatment. All patients were treated with at least 3 doses of monthly subcutaneous injections of omalizumab. Fifteen patients achieved a UAS7 of 6 or less after 3 doses of monthly omalizumab injections. Seven of those 15 patients received an additional 1 to 3 doses and all ended up with a UAS7 of less than 2 at the 24-week follow-up. A sustained response to maintenance treatment after 24 weeks was observed in 5 patients with individual tailoring of treatment duration and dosing interval. Conclusion Omalizumab is an effective and safe treatment for antihistamine refractory CSU. Maintenance therapy with individual tailoring of the treatment duration and interval is possible. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma is an aggressive non-Hodgkin lymphoma subtype which requires immediate treatment. Standard treatment is usually a combined immune chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Since R-CHOP was approved, several attempts to combine it with novel agents and/or use them as maintenance therapy failed to improve the outcome. Recently, maintenance with lenalidomide after standard immune chemotherapy showed promising results. This review discusses the most pertinent published and running studies, analyzing study design, results, and practicality. [ABSTRACT FROM AUTHOR]

This study aimed to investigate remission following the treatment of schizophrenia patients with risperidone. Clinically stabilized patients with schizophrenia (n = 374) were randomly assigned to 4-week, 26-week, or no-dose-reduction groups, in which the baseline risperidone dose was continued for 4, 26, or all weeks during 1-year period. The ‘Positive and Negative Syndrome Scale’ (PANNS) was assessed at baseline and monthly for six months, followed by every two months until the last recruited patient completed 1-year follow-up. Symptomatic remission was defined according to criteria established by the Schizophrenia Working Group. A Generalized Linear Mixed Model indicated significant variation in remission over time, which increased after baseline in the entire group (F = 49.32, df = 1, 3114, P < 0.001). The overall length of risperidone treatment (F = 4.34, df = 1, 416, P = 0.038) and the duration of illness (F = 8.51, df = 1, 359, P = 0.004) had significantly negative effects upon remission. Baseline remission patients were associated with a significantly increased time to relapse compared with the baseline of non-remission patients over a one year follow up period (F = 5.74, df = 1, 367, P = 0.017). One-year risperidone maintenance treatment increased remission rates in schizophrenia. A shorter illness duration, risperidone treatment length, and a lower total PANSS score were clinically useful predictors of remission. Achieving remission may postpone relapse. [ABSTRACT FROM AUTHOR]

• JAVELIN Bladder 100 studied avelumab first-line maintenance in urothelial carcinoma. • Avelumab maintenance prolonged survival in patients with urothelial carcinoma. • We report results from the Asian subgroup of JAVELIN Bladder 100. • Efficacy benefits in the Asian subgroup were consistent with the overall population. • No new safety signals specific to Asian patients were identified. The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab first-line maintenance + best supportive care (BSC) vs. BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with first-line platinum-containing chemotherapy. Here, efficacy and safety were assessed from the initial analysis of the JAVELIN Bladder 100 trial (data cutoff October 21, 2019) in patients enrolled in Asian countries. Patients with locally advanced or metastatic UC that had not progressed with 4 to 6 cycles of first-line platinum-containing chemotherapy (gemcitabine + cisplatin or carboplatin) were randomized 1:1 to receive avelumab first-line maintenance + BSC or BSC alone, stratified by best response to first-line chemotherapy and visceral vs. nonvisceral disease when initiating first-line chemotherapy. The primary endpoint was OS assessed from randomization in all patients and patients with PD-L1+ tumors (Ventana SP263 assay). Secondary endpoints included progression-free survival (PFS) and safety. A total of 147 patients in JAVELIN Bladder 100 were enrolled in Asian countries (Hong Kong, India, Japan, South Korea, and Taiwan). In this Asian subgroup, 73 and 74 patients received avelumab + BSC or BSC alone, respectively. Median OS was 25.3 months (95% CI, 18.6 to not estimable [NE]) in the avelumab + BSC arm vs. 18.7 months (95% CI, 12.8–NE) in the BSC alone arm (hazard ratio [HR], 0.74 [95% CI, 0.43–1.26]); median PFS was 5.6 months (95% CI, 2.0–7.5) vs. 1.9 months (95% CI, 1.9–1.9), respectively (HR, 0.58 [95% CI, 0.38–0.86]). In the avelumab + BSC vs. BSC alone arms, grade ≥3 treatment-emergent adverse events (any causality) occurred in 44.4% vs. 16.2%, respectively. The most common grade ≥3 treatment-emergent adverse events in the avelumab + BSC arm were anemia (9.7%), amylase increased (5.6%), and urinary tract infection (4.2%). Efficacy and safety results for avelumab first-line maintenance in the Asian subgroup of JAVELIN Bladder 100 were generally consistent with those in the overall trial population. These data support the use of avelumab first-line maintenance as standard of care for Asian patients with advanced UC that has not progressed with first-line platinum-containing chemotherapy. NCT02603432 [ABSTRACT FROM AUTHOR]

BackgroundHeroin dependence is associated with high mortality. Opioid agonist treatment (OAT) with methadone or buprenorphine has strong evidence for treatment of this relapsing condition. In our setting, OAT has been associated with strict and demanding intake procedures, often with requirements of social stability, but also high, approximately 80 percent 12-month retention rates. In a recent randomized controlled trial, we demonstrated high rates of successful rapid referral from a syringe exchange programme (SEP) to treatment with methadone or buprenorphine, including actual treatment initiation. The objectives of this study were to assess 12-month retention rates, in order to assess whether a novel referral program of current drug users at a SEP would achieve retention rates comparable to more traditional intake procedures.MethodsThe present report is a 12-month follow-up of 71 patients who successfully started treatment with methadone or buprenorphine/naloxone. Patient data from baseline and at 12 months were collected.ResultsOut of the 71 patients who started treatment, 58 (82%) were still in treatment after 12 months.ConclusionThis was a population, referred from a SEP, with a high drug use severity on admission and no pretreatment requirement for social stability, but there were still high retention rates at 12 months comparable to regular opioid agonist clinics in our setting.

Lung cancer is the leading cause of death from cancer in the world. The treatment remains one of the most challenging tasks in the medical world. The discovery and development of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) have had a major impact in the treatment of non small cell lung cancer (NSCLC). But the efficacy of EGFR-TKI in EGFR wild-type patients is limited, and the limited EGFR mutation incidence also prompts researchers to study what is the best treatment choice for patients with NSCLC who are negative for EGFR mutations. This review will discuss the research status in treatment choice for EGFR wild-type NSCLC.

Background: The phase 3 CAIRO3 study showed that capecitabine plus bevacizumab (CAP-B) maintenance treatment after six cycles capecitabine, oxaliplatin, and bevacizumab (CAPOX-B) in metastatic colorectal cancer (mCRC) patients is effective, without compromising quality of life. In this post hoc analysis with updated follow-up and data regarding sidedness, we defined subgroups according to RAS/BRAF mutation status and mismatch repair (MMR) status, and investigated their influence on treatment efficacy. Patients and methods: A total of 558 patients with previously untreated mCRC and stable disease or better after six cycles CAPOX-B induction treatment were randomised to either CAP-B maintenance treatment (n=279) or observation (n=279). Upon first progression, patients were to receive CAPOX-B reintroduction until second progression (PFS2, primary end point). We centrally assessed RAS/BRAF mutation status and MMR status, or used local results if central assessment was not possible. Intention-to-treat stratified Cox models adjusted for baseline covariables were used to examine whether treatment efficacy was modified by RAS/BRAF mutation status. Results: RAS, BRAF mutations, and MMR deficiency were detected in 240/420 (58%), 36/381 (9%), and 4/279 (1%) patients, respectively. At a median follow-up of 87 months (IQR 69-97), all mutational subgroups showed significant improvement from maintenance treatment for the primary end point PFS2 [RAS/BRAF wild-type: hazard ratio (HR) 0.57 (95% CI 0.39-0.84); RASmutant: HR 0.74 (0.55-0.98); V600EBRAF-mutant: HR 0.28 (0.12-0.64)] and secondary end points, except for the RAS-mutant subgroup regarding overall survival. Adjustment for sidedness instead of primary tumour location yielded comparable results. Although right-sided tumours were associated with inferior prognosis, both patients with right- and left-sided tumours showed significant benefit from maintenance treatment. Conclusions: CAP-B maintenance treatment after six cycles CAPOX-B is effective in first-line treatment of mCRC across all mutational subgroups. The benefit of maintenance treatment was most pronounced in patients with RAS/BRAF wild-type and V600EBRAF-mutant tumours. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy, safety, and tolerability of aripiprazole, a dopamine D2 receptor partial agonist, as maintenance treatment in adolescent outpatients with schizophrenia.Method: This was a multicenter, double-blind, placebo-controlled, randomized withdrawal design trial. Participants 13 to 17 years of age with a diagnosis of schizophrenia (DSM-IV-TR) were first cross-titrated from their other oral antipsychotic(s) (4-6 weeks), then stabilized (7-21 weeks) on oral aripiprazole 10 to 30 mg/d, and finally randomized 2:1 to continuation of oral aripiprazole or to placebo in a double-blind maintenance phase (≤52 weeks). The primary endpoint was time from randomization to exacerbation of psychotic symptoms/impending relapse. Safety and tolerability were assessed.Results: Of 201 enrolled participants, 146 were randomized to aripiprazole (n = 98) or placebo (n = 48) in the double-blind maintenance phase. Treatment with aripiprazole was associated with a significantly longer time to exacerbation of psychotic symptoms/impending relapse compared with placebo (hazard ratio, 0.46 [95% CI = 0.24-0.88]; p = .016). Aripiprazole was associated with lower rates of serious treatment-emergent adverse events (TEAEs) versus placebo (3.1% versus 12.5%; p = .059) and severe TEAEs (2.0% versus 10.4%; p = .039). The rate of discontinuation due to TEAEs was lower with aripiprazole versus placebo (20.4% versus 39.6%, p = .014; number-needed-to-harm = 5.1). The incidences of extrapyramidal symptoms, weight gain, and somnolence were similar or lower with aripiprazole than with placebo, and no TEAEs related to elevated serum prolactin were reported. Based on Tanner staging, 27.6% of participants treated with aripiprazole and 16.7% of those who received placebo progressed one or two stages from baseline.Conclusion: Aripiprazole was observed to be safe and effective for the maintenance treatment of adolescents with schizophrenia.Clinical Trial Registration Information: Efficacy and Safety Study of Oral Aripiprazole in Adolescents With Schizophrenia; http://clinicaltrials.gov/; NCT01149655. [ABSTRACT FROM AUTHOR]

Background: Heroin dependence is associated with high mortality. Opioid agonist treatment (OAT) with methadone or buprenorphine has strong evidence for treatment of this relapsing condition. In our setting, OAT has been associated with strict and demanding intake procedures, often with requirements of social stability, but also high, approximately 80 percent 12-month retention rates. In a recent randomized controlled trial, we demonstrated high rates of successful rapid referral from a syringe exchange programme (SEP) to treatment with methadone or buprenorphine, including actual treatment initiation. The objectives of this study were to assess 12-month retention rates, in order to assess whether a novel referral program of current drug users at a SEP would achieve retention rates comparable to more traditional intake procedures. Methods: The present report is a 12-month follow-up of 71 patients who successfully started treatment with methadone or buprenorphine/naloxone. Patient data from baseline and at 12 months were collected. Results: Out of the 71 patients who started treatment, 58 (82%) were still in treatment after 12 months. Conclusion: This was a population, referred from a SEP, with a high drug use severity on admission and no pretreatment requirement for social stability, but there were still high retention rates at 12 months comparable to regular opioid agonist clinics in our setting. [ABSTRACT FROM AUTHOR]

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Introduction: This study examines factors associated with criminal engagement among patients in opioid maintenance treatment (OMT).Methods: Questionnaire data recorded annually among 5654 patients in the Norwegian OMT programme between 2005 and 2010 from seven regional treatment centres were available for analyses. Each patient answered approximately 4 times (mean: 4.11, SD: 1.46) generating a total of 18,538 questionnaires. The outcome variable of the study, engagement in criminal activity, was defined as whether a patient had been arrested, put in custody, been charged and/or convicted of a crime within the last 12months prior to the completion of the questionnaire. Three types of covariates were included: demographical, psychosocial and drug use-related. Missing data were imputed using Multivariate Imputation by Chained Equations and regression parameters were estimated by Generalized Estimation Equations to account for correlated measurements.Results: Having a full-time job (aOR: 0.47, CI: 0.34-0.64) or being a student/having a part-time job (aOR: 0.72, CI: 0.59-0.88) was negatively associated with ongoing criminal involvement, as did having a stable living situation (aOR: 0.70, CI: 0.57-0.87). On the other hand, being male (aOR: 1.83, CI: 1.59-2.10), younger (aOR: 0.96, CI: 0.95-0.97) and using illicit drugs regularly (aOR: 3.00, CI: 2.56-3.52) was positively associated with ongoing criminal activity while in OMT.Conclusions: Stable accommodation and participation in meaningful daily activity was found to be protective in terms of ongoing criminal engagement. Focus on these modifiable, psychosocial factors should therefore be an important and integral aspect of opioid maintenance treatment. [ABSTRACT FROM AUTHOR]

Objective: To compare the effect of maintenance pharmacotherapy on sustained abstinence rates between recently abstinent smokers with schizophrenia and bipolar disorder (SBD) and general population smokers without psychiatric illness.Method: We performed a person-level, pooled analysis of two randomized controlled trials of maintenance varenicline, conducted in adult smokers with SBD and general population smokers, controlling for severity of dependence. Smokers abstinent after 12-weeks of open varenicline treatment were randomly assigned to ≥12-weeks maintenance varenicline or identical placebo.Results: In those assigned to maintenance placebo, the abstinence rate at week-24 was lower in those with SBD than for those without psychiatric illness (29.4±1.1% vs. 61.8±0.4%, OR:0.26, 95% CI: 0.13, 0.52, p<0.001). In smokers assigned to maintenance pharmacotherapy, however, there was no effect of diagnosis on abstinence rates at week-24 (87.2±0.8% vs. 81.9±0.2%, OR: 1.68, 95% CI: 0.53, 5.32, p=0.38). Time to first lapse was shortest in those with SBD assigned to maintenance placebo (Q1=12days, 95%CI: 4, 16), longer in those without psychiatric illness assigned to maintenance placebo (Q1=17days, 95%CI: 17, 29), still longer in general-population smokers assigned to maintenance varenicline (Q1=88, 95% CI:58,91, and longest in those with SBD who received maintenance varenicline (Q1>95days, 95%CI:non-est), (Χ23df=96.99, p<0.0001; all pairwise comparisons p<0.001).Conclusions: Following a standard 12-week course of pharmacotherapy, people with schizophrenia and bipolar disorder were more likely to relapse to smoking without maintenance varenicline treatment. Maintenance pharmacotherapy could improve longer-term tobacco abstinence rates and reduce known smoking-related health disparities in those with SMI. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder is a chronic illness with a 2-year recurrence rate of approximately 50% among individuals receiving treatment in the community. The aim of this 18-month, open-label, continuation study was to evaluate the long-term safety and effectiveness of lurasidone in patients who initially presented with a major depressive episode associated with bipolar disorder, and who had completed at least 6 months of initial treatment with lurasidone. Methods: Patients with bipolar I depression were enrolled in one of three 6-week, double-blind, placebo-controlled trials (monotherapy with lurasidone, 1 study; adjunctive therapy with lurasidone; and lithium or valproate, 2 studies). Study completers were eligible for a 6-month, open-label extension study of lurasidone utilizing flexible daily doses of 20-120 mg; extension completers were then eligible for an additional 18 months of continuation treatment with flexible, once-daily doses of lurasidone in the range of 20-80 mg. Concomitant therapy with mood stabilizers was permitted throughout the open-label extension and continuation studies. Results: A total of 1199 patients entered, and 941 (78.5%) completed initial, double-blind, acute treatment, of whom 817/941 (86.8%) entered, and 559 (68.4%) completed the 6-month extension study; 122/559 patients (21.8%) entered the 18-month continuation study, of whom 19.7% of discontinued, including 6.6% due to adverse events and 1.6% due to insufficient efficacy. The mean dose of lurasidone during the 18-month continuation study was 61.8 mg/day, and the modal dose was 60 mg/day. Mean change in weight, from acute baseline to 18-month continuation endpoint was +0.8 kg (completers, n = 55); median changes in cholesterol and triglycerides were −3.0 mg/dL and +26.0 mg/dL, respectively. Based on a Kaplan-Meier analysis, the probability of relapse during 18 months of continuation treatment with lurasidone was estimated to be 18.3% in the monotherapy group and 29.1% in the adjunctive therapy group. Improvement in global illness severity was also maintained during 18 months of continuation therapy (CGI-S at continuation baseline, 2.1; 18-month completers, 1.7; LOCF-endpoint, 1.9). Conclusions: Up to 2 years of treatment with lurasidone was safe and well tolerated in this bipolar disorder population presenting with an index episode of depression. Improvement in depressive symptoms was maintained in the majority of patients treated with lurasidone, with relatively low rates of relapse, and with minimal effects on weight and metabolic parameters. [ABSTRACT FROM AUTHOR]

Background: Methadone maintenance treatment (MMT) of opiate addiction was introduced in Sweden 50years ago. The first Swedish programs were modeled after the original Dole and Nyswander program, with strict criteria for admittance into treatment, and have been shown to have positive effects on social and health variables, including mortality. During the last 11years, there have been a number of changes in the regulations controlling MMT-programs in Sweden, and the criteria for admittance are now much less strict compared to previous ones. This study aims to characterize the current MMT-programs with respect to mortality and to compare the results to those obtained in earlier periods.Methods: Persons entering into treatment in Stockholm county, between 2006 and 2011, were followed until September 2013 or until death occurred. Death rates for periods in treatment and out of treatment were determined and compared to rates for the general population. Proportional hazards models with treatment status as time-varying covariate were fitted to the data. A competing risk analysis was made to investigate the effects of MMT on drug-related mortality as compared to mortality from other causes. Mortality data for earlier periods were retrieved from the literature.Results: A total of 441 persons entered MMT during the time period. Of these 67 died during follow-up, the death rate being almost twenty times higher than in the general population. Not being in treatment was associated with a significantly increased hazard of dying (hazard ratio: 2.1, 95% confidence interval: 1.3-3.4). The hazard ratio was mainly increased for drug-related deaths (hazard ratio: 4.4 (2.1-9.2)).Conclusions: Mortality rates among persons who entered MMT-programs in Stockholm during 2006-2011 were not increased compared to persons in treatment twenty years ago. The mortality was significantly increased during periods off treatment. Changes in regulations that minimizes the time off treatment are therefore likely to reduce the mortality rates among clients of MMT-programs. [ABSTRACT FROM AUTHOR]

Objective: To determine efficacy of continued treatment with the serotonin norepinephrine reuptake inhibitor duloxetine on symptom reduction and functional improvement in outpatients with dysthymia.Method: Fifty outpatients with DSM-IV-TR diagnosed dysthymia who had participated in a 10 week double-blind, placebo-controlled study of duloxetine received open treatment for three months. Nineteen duloxetine responders continued duloxetine, 24 patients initially treated with placebo started open duloxetine treatment, and 7 duloxetine non-responders were treated with desvenlafaxine or bupropion, selected by clinician choice.Results: Patients continuing duloxetine maintained symptom improvement, 84% meeting response and 63% remission criteria at week 22. Patients initially treated with placebo showed similarly high levels of response (83%) and remission (62%) at week 22, and most duloxetine non-responders subsequently responded to other antidepressants. Duloxetine-continuation patients improved modestly between weeks 10 and 22 on measures of social and cognitive functioning and temperament. Despite this improvement concurrently across several functional domains, 66.7% of patients continuing duloxetine remained in the impaired range of functioning according to the Social Adjustment Scale (SAS).Conclusions: Continued duloxetine treatment appears to be effective in maintaining symptom response in dysthymic disorder, and has positive effects on social functioning. However, the majority of patients do not show normalization of functioning, even when controlling for remission status. Additional treatments should be considered to target residual impairments in social functioning in mood remitted patients with persistent depressive disorder. [ABSTRACT FROM AUTHOR]

Cobalamin deficiency is common in patients with Crohn's disease (CD). Intramuscular cobalamin continues to be the standard therapy for the deficiency and maintenance treatment in these patients, although oral route has been demonstrated to be effective in other pathologies with impaired absorption. Our aims were to evaluate the efficacy of oral therapy in the treatment of cobalamin deficiency and in long-term maintenance in patients with Crohn's disease. We performed a multicenter retrospective cohort study that included 94 patients with Crohn's disease and cobalamin deficiency. Seventy-six patients had B12 deficiency and 94.7% of them normalized their cobalamin levels with oral treatment. The most used dose was 1 mg/day, but there were no significant differences in treatment effectiveness depending on the dose used (≥1 mg/24 h vs. <1 mg/24 h). Eighty-two patients had previous documented B12 deficiency and were treated with oral B12 to maintain their correct cobalamin levels. After a mean follow-up of 3 years, the oral route was effective as maintenance treatment in 81.7% of patients. A lack of treatment adherence was admitted by 46.6% of patients in who the oral route failed. In conclusion, our study shows that oral cyanocobalamin provides effective acute and maintenance treatment for vitamin B12 deficiency caused by CD with or without ileum resection. [ABSTRACT FROM AUTHOR]

Background: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China., Methods: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0., Results: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA., Conclusions: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013-01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy. This consisted of 28-day cycles of pomalidomide 4 mg daily on days 1-21 and dexamethasone 20 mg weekly until progression. The primary endpoint was an improved response to treatment. A total of 75/100 patients reached therapy. The median follow-up time was 73 months. The median duration of treatment was 23.7 months. One third of patients improved their response from the initiation of treatment: 11%, 19% and 4% to a very good partial response, complete response or stringent complete response respectively. The median progression-free survival time was 33.2 months and the median overall survival time was not reached. Among the 75 patients, the reasons for pomalidomide discontinuation were progressive disease (54%), adverse events (AEs) (30%), investigator discretion (11%) and consent withdrawal (5%). Grade (G) 3/4 haematological AEs included neutropenia (51%) and lymphopenia (35%); G3/4 drug-related non-haematological AEs (>5%) comprised 13% infections. Long-term administration of pomalidomide and dexamethasone is feasible and one third of the patients improved their response., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: First-line maintenance strategies are a current matter of debate in the management of mCRC. Their impact on patient's health-related quality of life (HRQOL) has not yet been evaluated. The objective of this study was to assess whether differences in HRQOL during any active maintenance treatment compared with no maintenance treatment exist. Patient and methods: Eight hundred and thirty-seven patients were enrolled in the AIO KRK 0207 trial. Four hundred and seventy-two underwent randomization (after 24 weeks of induction treatment) into one of the maintenance arms: FP plus Bev (arm A), Bev alone (arm B), or no active treatment (arm C). HRQOL were assessed every 6 weeks during induction and maintenance treatment independent from treatment stop, delay, or modification, and also continued after progression, using the EORTC QLQ-C30, QLQ-CR29. The mean value of the global quality of life dimension (GHS/QoL) of the EORTC QLQ-C30, calculated as the average of all available time points after randomization was considered as prespecified main endpoint. Additionally, EORTC QLQ-C30 response scores were analyzed. Results: For HRQOL analysis, 413 patients were eligible (arm A: 136; arm B: 142, arm C: 135). Compliance rate with the HRQOL questionnaires was 95% at time of randomization and remained high during maintenance (98%, 99%, 97% and 97% at week 6, 12, 18 and 24). No significant differences between treatment arms in the mean GHS/QoL scores were observed at any time point. Also, rates of GHS/QoL score deterioration were similar (20.5%; 17.2% and 20.7% of patients), whereas a score improvement occurred in 36.1%; 43.8% and 42.1% (arms A, B and C). Conclusion: Continuation of an active maintenance treatment with FP/Bev after induction treatment was neither associated with a detrimental effect on GHS/QoL scores when compared with both, less active treatment with Bev alone or no active treatment. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate prolactin related symptoms (PRS) in individuals with schizophrenia during risperidone maintenance treatment for one year, as well as to identify the risk factors for PRS. Methods: In a multicenter, randomized, controlled, longitudinal study, clinically stabilized schizophrenia patients (N = 374) were randomized to a no-dose-reduction group (N = 129) and 4-week (N = 125) and 26-week (N = 120) reduction groups, in which the original dose was followed by a 50% reduction over 8 weeks and subsequently maintained. PRS were assessed via a scale of prolactin related adverse events, which included 16 items: menstrual cycle, menstrual period, menstrual volume, menstrual irregularities, amenorrhea, dysmenorrhea, postpartum lactation, gynecomastia, breast tenderness, sexual dysfunction, decreased sexual desire, erectile dysfunction, ejaculatory dysfunction, impotence, increased body hair, and acne. The occurrence of PRS was assessed at baseline and monthly for six months, followed by every two months. A mixed model was used. Results: PRS at baseline were reported in 18.4, 15.0, and 14.0% of the 4-week, 26-week, and no-dose-reduction groups, respectively. Female gender, younger age at onset, and the Positive and Negative Syndrome Scale (PANSS) total scores at entry predicted the development of PRS. The mixed model indicated that PRS were more severe in females and at a high dose. In the 237 patients who remained in the study after one year, the incidence of PRS decreased to 9.6, 11.1, and 7.6% in the 4-week, 26-week, and no-dose-reduction groups, respectively. Conclusion: These findings indicate that the PRS severity was alleviated during the one year treatment period because of the dose reduction. Attention should focus on the side effects of hyperprolactinemia during long-term treatment, especially with a high dose, females, younger age at onset, and more severe patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery.Design: Multicentre, randomised, double-blind, placebo-controlled trial.Setting: Twelve tertiary care centres in Spain.Population: A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm.Methods: Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first.Main Outcome Measures: Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality.Results: From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion.Conclusions: A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery.Tweetable Abstract: Maintenance progesterone in 258 women after arrested PTL showed no benefit. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to compare the effectiveness of Risperidone and Fluoxetine in combination with impulse control group therapy on improving of impulsivity, and relapse in heroin crack addicts under methadone maintenance therapy. Method: In a semi-experimental study, 39 heroin crack addicts who were under Methadone maintenance treatment selected of addiction withdrawal centers in Tehran. The selected sample was randomly assigned to three groups. First group was under (Risperidone 1 mg daily, impulse control group therapy for 8 sessions of 90 minutes, and methadone maintenance treatment), the second group was under (Fluoxetine 20 mg daily, impulse control group therapy for 8 sessions of 90 minutes, and methadone maintenance therapy), and the third group was under (impulse control group therapy for 8 sessions of 90 minutes, and methadone maintenance therapy). All participants completed the Barratt impulsivity scale (BIS-11) before and immediately after the end of intervention and follow up. Also, Morphine and stimulating drugs in urine were analyzed. Results: The results showed that total impulsivity scores was decreased in post-test but not in follow up. That is, impulsivity decreased in both experimental groups. Results also showed that relapse rate was not significantly differed. Conclusion: The combination of Fluoxetine with Methadone maintenance therapy and impulse control group therapy, was the most effective treatment on reduction of impulsivity, but not on relapse rate, in heroin crack abusers, in the short term.

Background/AimsWeekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse.Methods : Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks.Results : At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to