Problem gambling in psychotic disorders: A systematic review and meta-analysis of prevalence.

INTRODUCTION: Problem gambling (PBG) is more common in people with mental health disorders, including substance use, bipolar, and personality disorders, than in the general population. Although individuals with psychotic disorders might be expected to be more vulnerable to PBG, fewer studies have focused on this comorbidity. The aim of this review was to estimate the prevalence of PBG in people with psychotic disorders. METHODS: Medline (Ovid), EMBASE, PsycINFO (Ovid), CINAHL, CENTRAL, Web of science, and ProQuest were searched on November 1, 2023, without language restrictions. Observational and experimental studies including individuals with psychotic disorders and reporting the prevalence of PBG were included. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal for systematic reviews of prevalence data. The pooled prevalence of PBG was calculated using a fixed effects generalized linear mixed model and presented through forest plots. RESULTS: Of 1271 records screened, 12 studies (n = 3443) were included. The overall prevalence of PBG was 8.7% (95% CI = 7.8%-9.7%, I2 = 69%). A lower prevalence was found in studies with a low risk of bias (5.6%; 95% CI = 4.4%-7.0%) compared with studies with a moderate risk of bias (10.4%; 95% CI = 9.2%-11.7%). Different methods used to assess PBG also contributed to the heterogeneity found. CONCLUSION: This meta-analysis found substantial heterogeneity, partly due to the risk of bias of the included studies and a lack of uniformity in PBG assessment. Although more research is needed to identify those at increased risk for PBG, its relatively high prevalence warrants routine screening for gambling in clinical practice.

Problem gambling among people with first-episode psychosis: protocol for a prospective multicenter cohort study.

BACKGROUND: The limited available data suggest that the prevalence of problem gambling is increased among young adults with first-episode psychosis, possibly due in part to several risk factors for problem gambling that are common in this population. Aripiprazole, a widely used antipsychotic drug, has also been linked to cases of problem gambling, but causality remains uncertain. Although the consequences of problem gambling further hinder the recovery of people with first-episode psychosis, there is a paucity of research about this comorbidity and its risk factors. Additionally, to our knowledge, no screening instrument for problem gambling tailored to these individuals exists, contributing to its under-recognition. Further, treatment approaches for problem gambling adapted to this population are at an embryonic stage, while existing treatments effectiveness remains to be documented. Using an innovative screening and assessment procedure for problem gambling, this study aims to identify risk factors for problem gambling among people with first-episode psychosis and to document the effectiveness of standard treatment approaches. METHODS: This is a multicenter prospective cohort study conducted in two first-episode psychosis clinics, including all patients admitted between November 1st, 2019, and November 1st, 2023, followed for up to 3 years until May 1st, 2024. These 2 clinics admit approximately 200 patients annually, for an expected sample size of 800 individuals. The primary outcome is the occurrence of a DSM-5 diagnosis of gambling disorder. All patients are screened and evaluated for problem gambling using a systematic procedure at admission, and every 6 months thereafter. Socio-demographic and clinical variables are prospectively extracted from the patients' medical records. The nature and effectiveness of treatments for problem gambling offered to affected individuals are also documented from medical records. Survival analyses with Cox regression models will be used to identify potential risk factors for problem gambling. Descriptive statistics will document the effectiveness of treatments for problem gambling in this population. DISCUSSION: A better understanding of potential risk factors for problem gambling among people with first-episode psychosis will allow for better prevention and detection of this neglected comorbidity. Results of this study will also hopefully raise clinicians' and researchers' awareness and serve as the basis to adapted treatments that will better support recovery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05686772. Retrospectively registered, 9 January 2023.

Neuropathic Pain After Dental Implant Surgery: Literature Review and Proposed Algorithm for Medicosurgical Treatment.

The objective of this study is to establish an algorithm for the medicosurgical treatment of dental implant-induced neuropathic pain. The methodology was based on the good practice guidelines from the French National Authority for Health: the data were searched on the Medline database. A working group has drawn up a first draft of professional recommendations corresponding to a set of qualitative summaries. Consecutive drafts were amended by the members of an interdisciplinary reading committee. A total of 91 publications were screened, of which 26 were selected to establish the recommendations: 1 randomized clinical trial, 3 controlled cohort studies, 13 case series, and 9 case reports. In the event of the occurrence of post-implant neuropathic pain, a thorough radiological assessment by at least a panoramic radiograph (orthopantomogram) or especially a cone-beam computerized tomography scan is recommended to ensure that the tip of the implant is placed more than 4 mm from the anterior loop of the mental nerve for an anterior implant and 2 mm from the inferior alveolar nerve for a posterior implant. Very early administration of high-dose steroids, possibly associated with partial unscrewing or full removal of the implant preferably within the first 36-48 hours after placement, is recommended. A combined pharmacological therapy (anticonvulsants, antidepressants) could minimize the risk of pain chronicization. If a nerve lesion occurs in the context of dental implant surgery, treatment should be initiated within the first 36-48 hours after implant placement, including partial or full removal of the implant and early pharmacological treatment.

Problem Gambling Associated With Aripiprazole in First-Episode Psychosis Patients: A Series of 6 Case Reports.

BACKGROUND: Aripiprazole (ARI), an antipsychotic drug used to treat various mental health disorders, has recently been associated with the emergence of problem gambling (PBG). However, few cases have been reported in the schizophrenia-related psychotic disorders population, and even fewer provided sufficient details to systematically assess the causality of the association. METHODS: This article describes 6 cases with first-episode psychosis in whom PBG emerged while on ARI. Detailed information was gathered from clinical staff and patients' families to systematically assess the causal link between ARI and the emergence of PBG using the Naranjo and Liverpool Adverse Drug Reaction scales. FINDINGS: Five of these cases were previously diagnosed with a substance use disorder and/or cluster B personality traits. Five had received a more potent dopaminergic antagonist treatment before being switched to ARI. Two of them had presented PBG before being diagnosed with a psychotic disorder. The level of certainty about the causal role of ARI varied from possible to certain, and in 4 cases, the 2 scales yielded different ratings. IMPLICATIONS: Although these cases suggest that ARI may be associated with the emergence of PBG in the early course of schizophrenia-related psychotic disorders, they cannot prove the causality or the strength of this association. They provide the impetus to perform adequately powered and well-controlled prospective studies to draw more definite conclusion about the causality of this association and, in the meantime, further emphasize the need to carefully assess PBG in this population.

Psychological Vulnerability and Problem Gambling: The Mediational Role of Cognitive Distortions.

Despite numerous studies demonstrating the influence of cognitive distortions on gambling problem severity, empirical data regarding the role of psychological vulnerability on the latter is limited. Hence, this study assesses the mediating effect of cognitive distortions between psychological vulnerability (personality and mood), and gambling problem severity. It also verifies whether the relationships between these variables differs according to the preferred gambling activity. The sample is composed of 272 male gamblers [191 poker players; 81 video lottery terminal (VLT) players] aged between 18 and 82 years (M = 35.2). Bootstrap analysis results revealed that cognitive distortions mediate the effect of narcissism on gambling problem severity for both groups. The level of depression for VLT players significantly predicted gambling problem severity, both directly and indirectly via the mediating effect of cognitive distortions. Mediation analyses also indicated that narcissism had an indirect impact on problem gambling through cognitive distortions for both groups. These findings suggest that certain vulnerabilities related to personality and mood may influence cognitive distortion intensity and gambling problem severity. In addition, psychological vulnerabilities could differ based on preferred gambling activity. These results may be useful for prevention policies, identifying high risk gamblers and planning psychological interventions.

Efficacy of a Self-Help Treatment for At-Risk and Pathological Gamblers.

Available evidence suggests that self-help treatments may reduce problem gambling severity but inconsistencies of results across clinical trials leave the extent of their benefits unclear. Moreover, no self-help treatment has yet been validated within a French Canadian setting. The current study therefore assesses the efficacy of a French language self-help treatment including three motivational telephone interviews spread over an 11-week period and a cognitive-behavioral self-help workbook. At-risk and pathological gamblers were randomly assigned to the treatment group (n = 31) or the waiting list (n = 31). Relative to the waiting list, the treatment group showed a statistically significant reduction in the number of DSM-5 gambling disorder criteria met, gambling habits, and gambling consequences at Week 11. Perceived self-efficacy and life satisfaction also significantly improved after 11 weeks for the treatment group, but not for the waiting list group. At Week 11, 13% of participants had dropped out of the study. All significant changes reported for the treatment group were maintained throughout 1, 6 and 12-month follow-ups. Results support the efficacy of the self-help treatment to reduce problem gambling severity, gambling behaviour and to improve overall functioning among a sample of French Canadian problem gamblers over short, medium and long term. Findings from this study lend support to the appropriateness of self-help treatments for problem gamblers and help clarify inconsistencies found in the literature. The low dropout rate is discussed with respect to the advantages of the self-help format. Clinical and methodological implications of the results are put forth.

Cognitive Characteristics of Strategic and Non-strategic Gamblers.

Participation in strategic and non-strategic games is mostly explained in the literature by gender: men gamble on strategic games, while women gamble on non-strategic games. However, little is known about the underlying cognitive factors that could also distinguish strategic and non-strategic gamblers. We suggest that cognitive style and need for cognition also explain participation in gambling subtypes. From a dual-process perspective, cognitive style is the tendency to reject or accept the fast, automatic answer that comes immediately in response to a problem. Individuals that preferentially reject the automatic response use an analytic style, which suggest processing information in a slow way, with deep treatment. The intuitive style supposes a reliance on fast, automatic answers. The need for cognition provides a motivation to engage in effortful activities. One hundred and forty-nine gamblers (53 strategic and 96 non-strategic) answered the Cognitive Reflection Test, Need For Cognition Scale, and socio-demographic questions. A logistic regression was conducted to evaluate the influence of gender, cognitive style and need for cognition on participation in strategic and non-strategic games. Our results show that a model with both gender and cognitive variables is more accurate than a model with gender alone. Analytic (vs. intuitive) style, high (vs. low) need for cognition and being male (vs. female) are characteristics of strategic gamblers (vs. non-strategic gamblers). This study highlights the importance of considering the cognitive characteristics of strategic and non-strategic gamblers in order to develop preventive campaigns and treatments that fit the best profiles for gamblers.

Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma.

BACKGROUND: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. METHODS: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT. RESULTS: The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers. CONCLUSIONS: As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. (Funded by Intergroupe, Francophone du Myélome and Celgene; FIRST ClinicalTrials.gov number, NCT00689936; European Union Drug Regulating Authorities Clinical Trials number, 2007-004823-39.).

A noninterventional observational registry of patients with multiple myeloma treated with lenalidomide in Taiwan.

BACKGROUND/PURPOSE: The incidence of multiple myeloma in Asia has risen in the past 30 years. Lenalidomide, an IMiD immunomodulatory agent, has improved the overall survival in patients with relapsed/refractory multiple myeloma (RRMM) when used with dexamethasone versus dexamethasone alone. This observational registry (T-CC-MM-009; NCT01752075) assessed the safety and efficacy of lenalidomide plus dexamethasone in a large Chinese population of patients with RRMM. METHODS: This registry followed the first 100 patients treated with lenalidomide plus dexamethasone in Taiwan. Patients were ≥18 years old and had ≥1 prior treatment. The recommended starting dose for the first four 28-day cycles was 25 mg lenalidomide on days 1-21 and 40 mg dexamethasone on days 1-4, 9-12, and 17-20. Thereafter, dexamethasone was given on days 1-4 only. The primary objective was safety; secondary objectives were efficacy, lenalidomide dosage, and reasons for discontinuation. RESULTS: The median duration of treatment was 34.6 weeks, and 75.5% completed ≥3 cycles. Most patients (82.7%) experienced ≥1 treatment-related adverse event; the most commonly reported were neutropenia (23.5%), thrombocytopenia (19.4%), anemia (16.3%), fatigue (16.3%), and hypoesthesia (15.3%). Bleeding events (25.5% of patients) were mostly grade 1/2 (80%). Three patients (3%) had venous thromboembolic events. Two invasive second primary malignancies were reported; however, time to onset was <1 year, suggesting they may not be related to lenalidomide. The overall response rate was 34.7%; median time to disease progression was 20.5 months. CONCLUSION: These data confirm the safety and efficacy of lenalidomide plus dexamethasone for patients with RRMM in Taiwan.

Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study.

This multicenter, open-label, randomized phase 2 study assessed the efficacy and safety of pomalidomide (POM) with/without low-dose dexamethasone (LoDEX) in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior therapies (including lenalidomide [LEN] and bortezomib [BORT]) and had progressed within 60 days of their last therapy were randomized to POM (4 mg/day on days 1-21 of each 28-day cycle) with/without LoDEX (40 mg/week). The primary end point was progression-free survival (PFS). In total, 221 patients (median 5 prior therapies, range 1-13) received POM+LoDEX (n = 113) or POM (n = 108). With a median follow-up of 14.2 months, median PFS was 4.2 and 2.7 months (hazard ratio = 0.68, P = .003), overall response rates (ORRs) were 33% and 18% (P = .013), median response duration was 8.3 and 10.7 months, and median overall survival (OS) was 16.5 and 13.6 months, respectively. Refractoriness to LEN, or resistance to both LEN and BORT, did not affect outcomes with POM+LoDEX (median PFS 3.8 months for both; ORRs 30% and 31%; and median OS 16 and 13.4 months). Grade 3-4 neutropenia occurred in 41% (POM+LoDEX) and 48% (POM); no grade 3-4 peripheral neuropathy was reported. POM+LoDEX was effective and generally well tolerated and provides an important new treatment option for RRMM patients who have received multiple prior therapies. This trial was registered at www.clinicaltrials.gov as #NCT00833833.

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma.

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 - < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 - < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30.

Overall survival of relapsed and refractory multiple myeloma patients after adjusting for crossover in the MM-003 trial for pomalidomide plus low-dose dexamethasone.

In the phase III MM-003 trial, pomalidomide plus low-dose dexamethasone (POM+LoDEX) improved overall survival (OS) versus high-dose dexamethasone (HiDEX) in 455 patients with relapsed and refractory multiple myeloma (RRMM) after treatment with bortezomib and lenalidomide. Here, a two-stage Weibull method was used to adjust for the crossover of patients in the HiDEX arm to pomalidomide-based therapy. The adjusted difference in median OS between patients in the POM+LoDEX and HiDEX arms was 7·0 months (12·7 vs. 5·7 months, respectively). These findings provide important evidence for understanding the clinical efficacy of pomalidomide on OS benefits seen in RRMM patients.

Continuous lenalidomide treatment for newly diagnosed multiple myeloma.

BACKGROUND: Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma. METHODS: We randomly assigned patients who were ineligible for transplantation to receive MPR-R (nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [152 patients]) or to receive MPR (153 patients) or MP (154 patients) without maintenance therapy. The primary end point was progression-free survival. RESULTS: The median follow-up period was 30 months. The median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months; hazard ratio, 0.49; P<0.001) or MP (13 months; hazard ratio, 0.40; P<0.001). Response rates were superior with MPR-R and MPR (77% and 68%, respectively, vs. 50% with MP; P<0.001 and P=0.002, respectively, for the comparison with MP). The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age (P=0.001 for treatment-by-age interaction). After induction therapy, a landmark analysis showed a 66% reduction in the rate of progression with MPR-R (hazard ratio for the comparison with MPR, 0.34; P<0.001) that was age-independent. During induction therapy, the most frequent adverse events were hematologic; grade 4 neutropenia was reported in 35%, 32%, and 8% of the patients in the MPR-R, MPR, and MP groups, respectively. The 3-year rate of second primary tumors was 7% with MPR-R, 7% with MPR, and 3% with MP. CONCLUSIONS: MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation, with the greatest benefit observed in patients 65 to 75 years of age. (Funded by Celgene; MM-015 ClinicalTrials.gov number, NCT00405756.).

Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib.

This phase 1 dose-escalation study determined the maximum tolerated dose (MTD) of oral pomalidomide (4 dose levels) administered on days 1 to 21 of each 28-day cycle in patients with relapsed and refractory multiple myeloma (RRMM). After four cycles, patients who progressed or had not achieved minimal response (serum and urine M-protein reduction of ≥ 25% and ≥ 50%) could receive dexamethasone 40 mg per week. Safety and efficacy were evaluated. Thirty-eight patients who had received both bortezomib and lenalidomide (median 6 prior therapies) were enrolled; 63% were refractory to both lenalidomide and bortezomib. There were four dose-limiting toxicities (grade 4 neutropenia) at 5 mg per day and so the MTD was 4 mg per day. Rates of peripheral neuropathy and venous thromboembolism were low (≤ 5%). Among the 38 patients enrolled (including 22 with added dexamethasone), 42% achieved minimal response or better, 21% achieved partial response or better, and 3% achieved complete response. Median duration of response, progression-free survival, and overall survival were 4.6, 4.6, and 18.3 months, respectively. Pomalidomide 4 mg per day on days 1 to 21 of each 28-day cycle, with or without dexamethasone (40 mg/week), has encouraging activity with manageable toxicity in RRMM, including those refractory to both lenalidomide and bortezomib. This study is registered at http://www.clinicaltrials.gov as #NCT00833833.

Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone.

Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P <0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or high-dose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2% versus 9.7%) and those with del(17p) (31.8% versus 4.3%), whereas it was similar in patients with t(4;14) (15.9% versus 13.3%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma and del(17p) and/or t(4;14). This study is registered at ClinicalTrials.gov as NCT01311687 and with EudraCT as 2010-019820-30.

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma.

Pomalidomide is a distinct oral IMiD(®) immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30.

Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial.

BACKGROUND: Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide. Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma, but synergistic effects have been noted when combined with dexamethasone. We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients. METHODS: This multicentre, open-label, randomised phase 3 trial was undertaken in Australia, Canada, Europe, Russia, and the USA. Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma, and had failed at least two previous treatments of bortezomib and lenalidomide. They were assigned in a 2:1 ratio with a validated interactive voice and internet response system to either 28 day cycles of pomalidomide (4 mg/day on days 1-21, orally) plus low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally) or high-dose dexamethasone (40 mg/day on days 1-4, 9-12, and 17-20, orally) until disease progression or unacceptable toxicity. Stratification factors were age (≤75 years vs >75 years), disease population (refractory vs relapsed and refractory vs bortezomib intolerant), and number of previous treatments (two vs more than two). The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01311687, and with EudraCT, number 2010-019820-30. FINDINGS: The accrual for the study has been completed and the analyses are presented. 302 patients were randomly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone. After a median follow-up of 10·0 months (IQR 7·2-13·2), median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months (95% CI 3·6-4·7) versus 1·9 months (1·9-2·2) with high-dose dexamethasone (hazard ratio 0·48 [95% CI 0·39-0·60]; p<0·0001). The most common grade 3-4 haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups were neutropenia (143 [48%] of 300 vs 24 [16%] of 150, respectively), anaemia (99 [33%] vs 55 [37%], respectively), and thrombocytopenia (67 [22%] vs 39 [26%], respectively). Grade 3-4 non-haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups included pneumonia (38 [13%] vs 12 [8%], respectively), bone pain (21 [7%] vs seven [5%], respectively), and fatigue (16 [5%] vs nine [6%], respectively). There were 11 (4%) treatment-related adverse events leading to death in the pomalidomide plus low-dose dexamethasone group and seven (5%) in the high-dose dexamethasone group. INTERPRETATION: Pomalidomide plus low-dose dexamethasone, an oral regimen, could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma. FUNDING: Celgene Corporation.

[Prevalence of gambling habits in Gaspésie and Îles-de-la-Madeleine in 2009]. / [Prévalence des habitudes de jeu en Gaspésie et aux Îles-de-la-Madeleine en 2009].

UNLABELLED: OBJECTIF : Estimer la prévalence des habitudes aux jeux de hasard et d'argent (JHA), du jeu à risque (JAR) et du jeu pathologique probable (JPP) dans la région de la Gaspésie et des Îles-de-la-Madeleine (GIM) (Québec). MÉTHODE : Un sondage téléphonique portant sur les habitudes de jeu a été réalisé auprès de 1014 adultes résidents de la région de la GIM. Les participants ont été sélectionnés aléatoirement. L'échelle Problem Gambling Severity Index de l'Indice canadien du jeu excessif a servi à l'évaluation du jeu pathologique. RÉSULTATS : Quatre-vingt-cinq pour cent des répondants rapportent avoir joué à un JHA au cours de l'année précédente. Les activités les plus populaires sont l'achat de billets de loterie, la participation à des tirages et collectes de fonds, le bingo, les cartes ou jeux de société en famille ou avec des amis pour de l'argent, la loterie vidéo et les jeux de casino. Les taux de prévalence du JAR et du JPP s'élèvent à 1,5 % et 0,8 % respectivement. La loterie vidéo s'avère le jeu le plus souvent identifié comme étant problématique, suivi des loteries instantanées et ordinaires (par exemple, Lotto 6/49). CONCLUSION: Les habitudes de jeu des Gaspésiens et des Madelinots sont similaires à celles observées chez l'ensemble des Québécois. La discussion soulève entre autres la question de la validité de l'évaluation de la présence d'un problème de jeu parmi les membres de l'entourage, et certaines perceptions à risque, dont celle qu'il est impossible de développer un problème aux loteries instantanées et au bingo.

Problem Gambling Associated with Aripiprazole: A Nested Case-Control Study in a First-Episode Psychosis Program.

BACKGROUND: Aripiprazole has been linked to cases of problem gambling (PBG), but evidence supporting this association remains preliminary. Additionally, data specific to PBG in individuals with first-episode psychosis (FEP) receiving aripiprazole are limited to a few case reports, even though aripiprazole is widely used among this population that might be especially vulnerable to PBG. METHODS: To examine this association, a nested case-control study was conducted in a cohort of 219 patients followed at a FEP program located in the Quebec City, Quebec, Canada, metropolitan area. Fourteen cases meeting the PBG criteria according to the Problem Gambling Severity Index were identified and matched for gender and index date to 56 control subjects. RESULTS: In the univariable conditional logistic regression analysis, the use of aripiprazole was associated with an increased risk of PBG (odds ratio [OR] 15.2; 95% confidence interval [CI] 2.1-670.5). Cases were more likely to have a prior gambling history (either recreational or problematic) than controls at admittance in the program; they were also more frequently in a relationship and employed. After adjustment for age, relationship status, employment and Cluster B personality disorders, the use of aripiprazole remained associated with an increased risk of PBG (OR 8.6 [95% CI 1.5-227.2]). CONCLUSIONS: Findings from this study suggest that FEP patients with a gambling history, problematic or not, may be at increased risk of developing PBG when receiving aripiprazole. They also highlight the importance of systematically screening for PBG all individuals with psychotic disorders, as this comorbidity hinders recovery. While the results also add credence to a causal association between aripiprazole and PBG, further prospective studies are needed to address some of the limitations of this present study.