Randomized open-label study of second-generation antipsychotics for the treatment of schizophrenia: 104-week final results of the JUMPs study assessing treatment discontinuation, remission, and social functioning.

BACKGROUND: We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study. METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension). RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation. CONCLUSIONS: The 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment. CLINICAL TRIAL REGISTRATION: UMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012).

Discontinuation and loss to follow-up rates in clinical trials of intravitreal anti-vascular endothelial growth factor injections.

PURPOSE: Clinical trials are often designed to include homogenous, highly specific patient populations with many resources to reduce patient dropout. Results may not translate to real-world settings. We evaluated discontinuation and loss to follow-up (LTFU) rates in clinical trials of anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). METHODS: Retrospective meta-epidemiological study. The authors queried ClinicalTrials.gov for all completed trials of anti-VEGF injections for DME, AMD, or RVO. Of 658 trials identified, 582 were excluded for being non-interventional, <100 patients, terminating early, or missing study results. The remaining 76 trials of 27,823 patients were analyzed for discontinuation and LTFU rates. RESULTS: Mean discontinuation rate was 12.44% (SD 8.12%, range 0-54.12%), with higher rates among control (18.87%) than treatment arms (10.78%, p = .006). Mean LTFU rate was 1.84% (SD 1.78%, range 0-7.76%), with no differences by disease, treatment type, or treatment frequency. CONCLUSION: Discontinuation rates of major intravitreal anti-VEGF clinical trials were highly variable, suggesting even trials struggle with overall patient retention. Though trial LTFU rates were low, real-world outcomes may differ due to higher reported LTFU rates, which should be considered when extrapolating trial results to clinical practice.

Discontinuation and remission rates and social functioning in patients with schizophrenia receiving second-generation antipsychotics: 52-week evaluation of JUMPs, a randomized, open-label study.

AIM: Globally, evidence from short-term studies is insufficient for the guidelines to uniformly recommend a particular antipsychotic(s) for the maintenance treatment of schizophrenia. Therefore, long-term comprehensive evaluation of antipsychotics is required from a social rehabilitation perspective, especially for drugs that have not yet been studied. The Japan Useful Medication Program for Schizophrenia (JUMPs) is a large-scale, long-term naturalistic study to present pivotal 52-week data on the continuity of second-generation antipsychotics (SGA: aripiprazole, blonanserin, and paliperidone). METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 52-week study. Enrolled patients had schizophrenia, were ≥20 years old, and required antipsychotic treatment or switched from previous therapy. The primary endpoint was treatment discontinuation rate over 52 weeks. Secondary outcomes included remission rate, social functioning, and quality-of-life scores [Personal and Social Performance Scale (PSP) and EuroQol-5 dimensions], and safety. RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). The discontinuation rate (P = 0.9771) and remission rates (P > 0.05) over 52 weeks did not differ significantly between the three treatment groups. The discontinuation rates were 68.3%, 68.2%, and 65.5% in the aripiprazole, blonanserin, and paliperidone groups, respectively. Significant improvements (all P < 0.05) from baseline in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favored blonanserin. CONCLUSION: All three SGAs evaluated in this study showed similar treatment discontinuation rates in patients with chronic schizophrenia in Japan.

Levetiracetam monotherapy in children with epilepsy: Experience from a tertiary pediatric neurology center.

OBJECTIVES: Levetiracetam (LEV) is a second-generation antiepileptic drug with high efficacy and tolerability in children and adults with epilepsy. We aimed to retrospectively assess the long-term efficacy, tolerability, and safety of LEV monotherapy in children with epilepsy. METHODS: All patients who received LEV monotherapy at the Ankara University Children Hospital between January 2010 and June 2020 were evaluated. This retrospective pediatric cohort study determined the efficacy and safety of LEV monotherapy in 281 outpatients with epilepsy. RESULTS: There were 281 patients, 50.5% female, aged 5 months to 18 years with a mean age of 9 years. Of these, 48% of patients had idiopathic epilepsy, 40.6% had symptomatic epilepsy, and 11,4% had cryptogenic/genetic epilepsy. Primary generalized seizures occurred in 61.6% of patients, focal seizures in 19.6%, both generalized and focal seizures in 15,3%, focal to bilateral tonic-clonic seizures in 2.5%, and undefined type of seizure in 1.1%. A total of 22.8% patients had an accompanying extra neurological disease, mostly cardiological and hematological. The range of final daily dose was 10-71 mg/kg/day, with mean 29.5 mg/kg/day. Duration of therapy ranged from 7 days to 96 months, with median 12 months (IQR: 6-22). For the all cohort, a 6th month retention rate was 81%, a 12th month retention rate was 71.4%, and a 24th month retention rate was 61.8%. Eighty five percent of the patients had a seizure reduction of at least 50% and 55.9% of patients remained seizure-free for median 12 months treatment duration with LEV monotherapy. Improvement of electroencephalography (EEG) findings was found in 42% of patients on control EEGs. A total of 67 adverse events were documented in 45 (16%) patients. The most common adverse events were behavioral problems such as aggression (n:18) and irritability (n:17). The discontinuation rate due to adverse events was 2.5%, and due to inefficacy was 5.3%. CONCLUSION: The present study suggests that the high retention rates, high percentage of seizure reduction, the low discontinuation rate due to adverse events and inefficacy, and the relatively benign and transient profile of adverse events make LEV preferable as monotherapy in the pediatric population.

Prevalence and factors associated with early discontinuation rate of Implanon utilization among women who ever used Implanon in Kucha District Gamo Gofa Zone, Southern Ethiopia.

BACKGROUND: The promotion of contraception in countries with high birth rates has the potential to reduce poverty, hunger, maternal, and childhood deaths. Every year in sub-Saharan Africa approximately 14 million unintended pregnancies occurred and a sizeable proportion was due to poor use of short-term hormonal methods. Contraceptive hormonal implants are highly effective and suitable for almost all women at any stage of their reproductive lives. On the other hand, early discontinuation of the Implanon contraceptive method utilization is one of the foremost problems amid the family planning program. Early discontinuation of the Implanon contraceptive method and reasons for such discontinuation lingers the most significant anxiety for family planning programs. In unindustrialized countries, contraceptive discontinuation due to health concerns is generally higher; these complaints are often related to service quality. Hence, this study aimed to assess the prevalence and factors associated with early discontinuation of Implanon among women who ever used Implanon in Kucha district, Gamo Gofa Zone, Southern Ethiopia. METHODS: Implanon contraceptive device users were selected from the Kucha district using a cross-sectional community-based survey from January to March 2018. A total of 430 women were selected and data were collected through face-to-face interviews by using a pre-tested structured questionnaire. Data were cleaned, coded, and entered into Epi-Info version 7statistical software. Factors that showed association in a bivariate analysis that has a p value of less than 0.25 were entered into multiple logistic regression models for controlling confounding factors. The strength of statistical association was measured by adjusted odds ratio, at 95% confidence intervals, and p value < 0.05 were considered as statistically significant variables. RESULT: The result of this study revealed that the overall discontinuation rate of Implanon in the study was 34%. Variables having statistically significant association with Implanon discontinuation were women who never use a contraceptive method other than Implanon (AOR = 2.96, 95% CI 1.53-5.74), women who didn't make discussion with a partner (AOR = 3.32, 95% CI 1.57-7.04), poor counseling and follow up (AOR = 9.23, 95% CI 4.7-18.13), fear of side effects (AOR = 0.12, 95% CI 0.058- 0.24) and poor satisfaction of service (AOR = 5.2, 95% CI 2.77- 9.76) CONCLUSION: The overall early discontinuation rate of Implanon in the study area was high. The main factors associated with early discontinuation of Implanon were contraceptive ever use, discussion with partner, poor follow-up of counseling, fear of side effects, and un-satisfaction by the services given during the insertion rate of Implanon.

Discontinuation rates during long-term, second-generation antipsychotic long-acting injection treatment: A systematic review.

AIM: The aim of this review was to analyze the discontinuation rates during long-term treatment with second-generation antipsychotic long-acting injection (SGA-LAI) in adults with either schizophrenia spectrum or bipolar disorders. METHODS: A systematic search (PubMed, Scopus, and the Cochrane Library) of studies published in English (1 January 2001-12 October 2018) identified 1214 abstracts, which were analyzed independently by the author and two colleagues. Studies were retrieved and reviewed if they reported primary data on the discontinuation rate before the study end during treatment lasting ≥36 weeks. Data were extracted from 51 articles meeting the inclusion criteria. RESULTS: In all head-to-head comparisons, and studies on patients with schizophrenia spectrum or bipolar disorders, the discontinuation rate before the study end in patients treated with SGA-LAI was, at best, similar to that recorded in patients treated with first-generation antipsychotics in either oral or LAI formulations or with oral SGA. In particular, in most of the SGA-LAI long-term studies, the rate of premature dropout was higher than 50%. CONCLUSION: Reviewed data suggest that SGA-LAI show no clear superiority over less expensive drugs (including first-generation antipsychotic LAI and oral antipsychotic formulations) in reducing the risk of premature antipsychotic discontinuation. Thus, alternative strategies should be considered to improve medication persistence and lower discontinuation rates in patients with severe psychiatric disorders. Planning tailored, individualized, and integrated approaches (including frequent clinical evaluations, and behavioral or other flexible techniques adaptable to different settings and patients) may be an effective intervention for improving patient adherence in long-term pharmacological treatment regimens.

Differences in continuation rates and early removal between contraceptive and therapeutic use of the levonorgestrel-releasing intrauterine system 52 mg.

Objective: To investigate differences in continuation rates between contraceptive and therapeutic use of the levonorgestrel-releasing intrauterine system 52 mg (LNG-IUS) and factors associated with early removal.Methods: Study design: Retrospective consecutive cohort design.Cohort: Women with the insertion of the LNG-IUS for contraceptive or therapeutic use from 1 January 2006 through 1 January 2009 at the Zuyderland Medical Centre, The Netherlands, with a follow-up of 5 years. The continuation period and reasons of early removal were noted. Univariable and multivariable analysis were performed.Results: Follow-up was possible in 2481 women, 1855 (74.8%) in the contraception group, and 626 (25.2%) in the therapy group. Multivariable Cox proportional hazards models showed, that therapeutic use was associated with an increased risk of early removal of the LNG-IUS (HR 1.23; 95% CI 1.08-1.41), as was having one child (HR 1.20; 95% CI 1.04-1.38), and a decreased risk with advancing age (HR 0.96; 95% CI 0.95-0.97). In both groups, an unacceptable bleeding pattern and adverse events were the main reasons of early removal, resulting in very low continuation rates over the years.Conclusion: Therapeutic use, having one child and a younger age are independent risk factors of early removal of the LNG-IUS, in contrast with previous LNG-IUS use which is associated with a lower risk. In both the contraception group and the therapy group, the main reasons for LNG-IUS discontinuation are continuation with a new LNG-IUS, and no more need for an LNG-IUS (for contraception or therapy). An unacceptable bleeding pattern or adverse events are associated with the lowest continuation rates in both groups.

Discontinuation rate and adverse events after 1 year of vaginal pessary use in women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: To ascertain the rate of discontinuation after vaginal pessary use among pelvic organ prolapse patients. METHODS: We enrolled women suffering from pelvic organ prolapse who opted to use vaginal pessary as the first line of treatment and were fitted with a pessary at the urogynecological clinic in Khon Kaen University's Srinagarind Hospital (Thailand) during the period between 2010 and 2016. Patients' medical records were retrospectively reviewed. Patients were contacted by telephone if there were missing data or if more information was required. RESULTS: One hundred and forty women were included. The median age was 71.5 years (interquartile = 65.0, 77.0) and normal vaginal parity was 4.0 (interquartile =3.0, 6.0). The mean ± SD of BMI was 23.5± 3.6 kg/m2. Most of the women enrolled in the study (97.9%) were postmenopausal and many were at an advanced stage of prolapse (73.6%). Support pessaries were the most common treatment (95.0%). The discontinuation rate of pessary use after 1 year was 16.1%. The most common reason for discontinuing the vaginal pessary was frequent expulsion (26.3%). Abnormal vaginal discharge was the most common adverse effect after pessary insertion (17.1%). Lower BMI and history of hysterectomy were the significant risk factors for discontinuation of pessary use (0.76 [95%CI 0.62-0.93] and 15.89 [95%CI 1.67-151.02] respectively). CONCLUSIONS: The discontinuation rate of pessary use in the case of pelvic organ prolapse was low after 1 year. Abnormal vaginal discharge was the most common adverse side effect. Lower BMI and history of hysterectomy were factors significantly associated with the discontinuation.

The real impact of telaprevir dosage on the antiviral and side effects of telaprevir, pegylated interferon and ribavirin therapy for chronic hepatitis C patients with HCV genotype 1.

Triple therapy with telaprevir, pegylated interferon and ribavirin has been reported to improve antiviral efficacy but have potentially severe adverse effects in patients with chronic hepatitis C. To avoid the severe effects of telaprevir, lowering the dose has been suggested. However, impact of dosage changes on antiviral and adverse effects remains unclear. One hundred and sixty-six Japanese patients with HCV genotype 1 were treated with triple therapy. The drug exposure of each medication was calculated by averaging the dose actually taken. The overall SVR rate was 82%. The telaprevir discontinuation rate was 26%. The factors associated with discontinuation were an older age (≥65 y.o.) and a higher average dose during treatment. The telaprevir discontinuation rates were 42%, 25% and 14% in patients at ≥35, 25-35 and <25 mg/kg/day of telaprevir and 58% in older patients at ≥35 mg/kg/day of TVR. The factors associated with SVR were treatment-naïve, relapse to previous treatment, higher average telaprevir dose during treatment and completion of treatment. The SVR rate was higher, at 91%, in patients at 25-35 mg/kg/day of telaprevir than the 71% and 78% observed in those at <25 and ≥35 mg/kg/day of drug. In Japanese patients, a mean telaprevir dose of 25-35 mg/kg/day during treatment can augment its efficacy in triple therapy for patients with HCV genotype 1.

Observational study on adjuvant trastuzumab in HER2-positive early breast cancer patients.

AIM: This observational study investigates the use of adjuvant trastuzumab (AT) in HER2-positive breast cancer patients in a real-life setting, focusing on relapse and discontinuation rates. PATIENTS & METHODS: Data on a group of HER2-positive patients collected from 13 oncology centers of northeast Italy were analyzed. RESULTS: In total, 1245 patients were analyzed. 13.1% of patients were excluded from AT because of comorbidities, age, tumor stage, refusal or other reasons; 8.2% of patients who received AT interrupted the therapy, mainly for toxicity. Overall the relapse rate was 10.9% in the AT-treated population versus 22.6% in nontreated patients (follow-up: 37.4 and 62.1 months, respectively). Disease-free survival (DFS) was lower in AT-relapsed patients than in not-relapsed. Statistical analysis showed a correlation between DFS and estrogen receptor status in AT-treated patients. CONCLUSION: Relapse rates are lower in clinical setting compared to clinical trials. Overall, AT is effective in HER2-positive early-stage breast cancer patients.

Postoperative use and early discontinuation of intravenous lidocaine in spine patients.

PURPOSE: Our institution employs a multimodal approach to manage postoperative pain after spine surgery. It involves continuous intravenous (IV) lidocaine until the morning of postoperative day two. This study aimed to determine the rate and reasons for early discontinuation of IV lidocaine in our spine patients. METHODS: We conducted a retrospective chart review and included pediatric patients who underwent ≥ 3-level spine surgery and received postoperative IV lidocaine from November 2019 to September 2022. For each case, we recorded the side effects of IV lidocaine, adverse events, time to discontinuation, and discontinuation rate. Subsequently, we used the same methodology to generate an adult cohort for comparison. RESULTS: We included 52 pediatric (18M:34F) and 50 (21M:29F) adult patients. The pediatric cohort's mean age was 14 years (8-18), and BMI 23.9 kg/m2 (13.0-42.8). The adult cohort's mean age was 61 years (29-82), and BMI 28.8 kg/m2 (17.2-44.1). IV lidocaine was discontinued prematurely in 21/52 (40.4%) of the pediatric cases and 26/50 (52.0%) of the adult cases (RR = 0.78, p = 0.2428). The side effects noted in the pediatric cases vary, including numbness, visual disturbance, and obtundation, but no seizures. The most common adverse events were fever and motor dysfunction. CONCLUSION: The early discontinuation rate of IV lidocaine use after spine surgery for children in our institution does not differ significantly from that of adults. The nature of the side effects and the reasons for discontinuation between the groups were similar. Thus, the safety profile of IV lidocaine for pediatric spine patients is comparable to adults.

Efficacy and Tolerance of Antipsychotics Used for the Treatment of Patients Newly Diagnosed with Schizophrenia: A Systematic Review and Meta-Analysis.

This systematic review compared the efficacy and tolerance of oral antipsychotics (APDs) used in the treatment of schizophrenia following the PRISMA-P© statement (n = 21). The primary outcomes of interest were clinical response measured with symptoms' improvement, tolerance to side effects and discontinuation reasons. There was better individual patients' response to aripiprazole vs. ziprasidone and quetiapine ((CDSS p = 0.04), BPRS p = 0.02, YMRS p = 0.001) and ziprasidone vs. quetiapine (CGI p = 0.02, CDSS p = 0.02). Aripiprazole was more tolerated than risperidone, ziprasidone and quetiapine (p < 0.05). Quetiapine was more tolerated than aripiprazole, ziprasidone and risperidone (p < 0.05). Ziprasidone was more tolerated than quetiapine haloperidol and olanzapine (p < 0.05). Risperidone was more tolerated than olanzapine (p = 0.03) and haloperidol was more tolerated than olanzapine and quetiapine (p < 0.05). Olanzapine caused less discontinuation than quetiapine; quetiapine caused less discontinuation than ziprasidone, aripiprazole and haloperidol; ziprasidone caused less discontinuation than quetiapine, aripiprazole and haloperidol; aripiprazole caused less discontinuation than quetiapine, ziprasidone and olanzapine and olanzapine caused less discontinuation than ziprasidone and haloperidol (p < 0.05). It was concluded that individual patient clinical response, tolerance to side effects and life-threatening side effects remain the most reliable basis for selecting and continuing the use of APD.

Antipsychotic Use: Cross-Sectional Opinion Survey of Psychiatrists in India and United Kingdom.

The aim of this survey of psychiatrists from the UK and India was to compare their opinions on antipsychotic medication choice and their experiences of such medications' effectiveness and tolerability in patients who were newly diagnosed with acute schizophrenia. Following ethical approval, a cross-sectional online survey of psychiatrists from the UK and India was conducted. Ninety-five responses were received from each country. The most selected first-line APDs in both countries were olanzapine (47.5%), risperidone (42.8%) and aripiprazole (25.3%). A total of 60% of psychiatrists from India (60%) and 48% from the UK (48%) selected 'medication efficacy' as the main factor in their choice. Reassessment and consideration to switch most often took place within 4-6 weeks (53.7%) and 3-6 months (11.6%). The major reasons for switching antipsychotic medications were poor clinical efficacy (69%) and lack of tolerability (45%). Nonadherence was the most common reason for relapse (90% of UK psychiatrists and 70% of Indian psychiatrists), followed by illicit drug use (27.6%). The most commonly reported side effects that led to nonadherence were weight gain (10.8%), drowsiness (10.4%), erectile dysfunction and movement disorders (equally 8.7%). It was concluded that olanzapine, risperidone and aripiprazole are the most commonly selected as the initial treatment choice by psychiatrists from India and the UK. They are perceived as widely effective and well tolerated.

PML risk is the main factor driving the choice of discontinuing natalizumab in a large multiple sclerosis population: results from an Italian multicenter retrospective study.

BACKGROUND: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients. MATERIALS AND METHODS: The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as "lack of efficacy", "progressive multifocal leukoencephalopathy (PML) risk" or "other". RESULTS: Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1 years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy [1682 (32.7% of 5151) vs 221 (4.3%), p < 0.001]; other reasons were identified for 99 (1.9%) patients. Patients discontinuing treatment were older, had longer disease duration and worse EDSS at the time of NTZ initiation and at last follow-up on NTZ treatment. The JCV index and EDSS at baseline were predictors for stopping therapy (HR 2.94, 95% CI 1.22-4.75; p = 0.02; HR 1.36, 95% CI 1.18-5.41; p = 0.04). CONCLUSIONS: Roughly 60% of MS patients stayed on NTZ treatment during the observation period. For those patients in whom NTZ discontinuation was required, it was mainly due to PML concerns.

Prevalence of contraceptive implant discontinuation among women who used implant in Ethiopia: Systemic review and meta-analysis.

The likelihood of contraceptive implant discontinuation is very common and varies worldwide. This high prevalence of discontinuation may also indicate problems with implementation of family planning programmes. Consequently, a significant number of women are exposed to conception after discontinuation. Although studies have been conducted in Ethiopia, there are inconsistencies across studies. Therefore, this meta-analysis aimed to estimate the pooled prevalence of contraceptive implant discontinuation among women in Ethiopia. Published articles from various electronic databases such as PubMed/MEDLINE, Google Scholar, Science Direct, AJOL and Cochrane library were systematically searched. All cross-sectional studies conducted on prevalence of contraceptive implant discontinuation and published up to 30 January 2022 were included in this review. To estimate the pooled prevalence, random effect model was used and a subgroup analysis was performed to identify the possible source of heterogeneity. Begg's and Egger's tests were used to identify possible publication bias. A total of 13 cross-sectional studies with 5012 participants were included. Significant heterogeneity was observed across studies (I2 = 98.2%). However, there was no evidence of publication bias (p = 0.066). The estimated pooled prevalence of contraceptive implant discontinuation in Ethiopia was found to be 36.95% (95% confidence interval = 27.6-46.3). A subgroup analysis by time of discontinuation indicated that 21.5%, 42.2% and 33.5% of contraceptive implant user discontinue within 12 months, 2.5 years and 3 years, respectively. This meta-analysis indicated that the prevalence of discontinuation of contraceptive implant was found to be high in Ethiopia. Therefore, strengthening the appropriate counselling prior to insertion and proper follow-up, independent choice will improve the proportion of implants retention.

How to reduce bacillus Calmette-Guérin discontinuation in patients with severe functional impairment.

Background: Severe functional impairment is often considered a contraindication to intravesical therapy for nonmuscle-invasive bladder cancer (NMIBC). A tailored intravesical bacillus Calmette-Guérin (BCG) procedure was evaluated in high-risk (HR)-NMIBC patients with severe functional impairment. Materials and methods: Patients with a Katz Index score of 2 or less and an initial diagnosis of HR-NMIBC with atraumatic insertion of a Foley-type indwelling catheter, bladder emptying, and BCG instillation were prospectively treated; after 2 hours, the bladder was emptied and the catheter was removed (group A).After propensity score matching, 52 patients in group A were compared with that of 52 consecutive patients in group B using a retrospective database, with similar baseline/oncological characteristics and treated with standard intermittent catheterization. Moreover, groups A and B were compared with that of 130 consecutive patients (group C) retrospectively evaluated, with similar oncological characteristics but with a Katz Index score of 3 or greater and treated with standard intermittent catheterization. Results: The discontinuation rates were 11.5%, 35%, and 9% in groups A, B, and C, respectively (A vs. B, log-rank score 42.52 [p < 0.05]; B vs. C, 107.6 [p < 0.05]; A vs. C, 3.45 [p > 0.05]). The overall adverse event rates were 38.5%, 57.7%, and 39.2%, respectively (A vs. B, p = 0.04; B vs. C, 0.03; A vs. C, 0.92). The rates of severe adverse events were 1.9%, 1.9%, and 1.5%, respectively, without statistically significant differences. The cumulative HR disease-free survival rates were 63.4%, 48%, and 69.2%, respectively (A vs. B, log-rank score 154.9 [p < 0.05]; B vs. C, 415 [p < 0.05]; A vs. C, 244 [p < 0.05]). Conclusions: A tailored intravesical instillation procedure may reduce BCG discontinuation and adverse effects.

A large-scale database study for the prescription status of a new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, in Japan.

BACKGROUND: A new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, was first approved for treating peripheral neuropathic pain in Japan in 2019. This is the first report on the prescription status of mirogabalin using a large-scale prescription database. RESEARCH DESIGN AND METHODS: The authors analyzed the prescription data of 12,924 patients prescribed mirogabalin between 1 June and 31 August 2020. The endpoints were the number of patients prescribed, prescription days, prescription doses, dose changes, co-prescription patterns, medication possession ratio (MPR), and treatment discontinuation rates (TDRs). RESULTS: Mirogabalin was newly prescribed to 7,914 patients in the 3-month study period. Most patients were prescribed mirogabalin at about 10 mg/day during the study period, and 30.9% of patients were prescribed ≥ 20 mg/day on Day 90 after the first prescription. The most frequently prescribed concomitant drug was celecoxib. The MPR (80 to 110%) was 86.2%, indicating good treatment adherence. The cumulative TDRs during ≤ 7 Days, Days 31-60, and 61-90 were 14.0%, 70.0%, and 77.9%, respectively. CONCLUSIONS: Mirogabalin was prescribed to a considerable number of patients. These results may be useful for optimizing mirogabalin use for patients with peripheral neuropathic pain in daily clinical practice. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000042592.

Non Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients Scheduled for Electrical Cardioversion: A Real-Life Propensity Score Matched Study.

AIM: The aim of the present study was to assess the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients undergoing electrical cardioversion (EC). METHODS: A propensity score-matched analysis was performed in order to identify two homogeneous groups including AF patients on NOACs and VKAs treatment scheduled for EC. The primary safety endpoint was major bleeding. The composite of stroke, transient ischemic attack (TIA) and systemic embolism (SE) was the primary effectiveness endpoint. The discontinuation rate of anticoagulant therapy was assessed. RESULTS: A total of 495 AF patients on NOACs therapy and scheduled for EC were compared to 495 VKAs recipients. No statistically significant differences in the incidence of both major bleeding (1.01% versus 1.4%; P= 0.5) and thromboembolic events (0.6% versus 0.8%; P= 0.7) were observed during a mean follow-up of 15 ± 3 months. The discontinuation rate of NOACs was significantly lower compared to VKAs (1.6% versus 3.6%, P=0.04). CONCLUSION: We showed a safe and effective clinical profile of NOACs among AF patients scheduled for electrical cardioversion in real-life setting. Patients on NOACs therapy showed a lower discontinuation rate compared to those on VKAs.

Association between discontinuation due to withdrawal of consent and use of long-acting injectable antipsychotics: A meta-analysis of randomized trials for schizophrenia.

We investigated the association between discontinuation due to withdrawal of consent (DWC) in schizophrenia trials and the use of long-acting injectable antipsychotics (LAI-APs). In two categorical meta-analyses of randomized controlled trials, we compared DWC: individual and pooled LAI-APs vs. (1) placebo and (2) oral antipsychotics (OAPs). We also performed conducted a single-group meta-analysis to calculate the average DWC and a meta-regression analysis to examine the association between the results of the meta-analyses and factors related to study design, treatment, and patients. We identified 52 studies (total adult patients = 18,675, LAI-APs = 12,613, placebo = 2,083, and OAPs = 3,979; median study duration = 32 weeks). DWC was higher for LAI-aripiprazole than for the placebo [risk ratio (95% confidence interval) = 1.70 (1.23-2.39)]. Neither pooled nor individual LAI-APs differed from the placebo for fluphenazine, olanzapine, paliperidone, and risperidone or from the OAPs for aripiprazole, fluphenazine, haloperidol, olanzapine, paliperidone, risperidone, and zuclopenthixol. The average DWC of each LAI-AP was as follows: LAI-aripiprazole = 10.98%, LAI-fluphenazine = 7.65%, LAI-flupenthixol = 3.33%, LAI-haloperidol = 6.71%, LAI-olanzapine = 10.50%, LAI-paliperidone = 10.38%, LAI-perphenazine = 7.06%, LAI-risperidone = 10.39%, LAI-zuclopenthixol = 4.45%, pooled LAI-APs = 9.88%, and placebo = 11.17%. Meta-regression analysis demonstrated that publication year (ß = 0.02), percentage of males (ß = 0.02), and mean age (ß = 0.05) were associated with an average DWC for pooled LAI-APs. Study duration (ß = -0.03), percentage of males (ß = 0.08), and patient status (ß = -0.85) were associated with an average DWC for LAI-aripiprazole. Presence of a placebo arm (ß = 1.60) was associated with an average DWC for LAI-fluphenazine. LAI-AP use was unlikely to be associated with DWC. Although the LAI-aripiprazole had a higher DWC than did the placebo, its average DWC was similar to other those of LAI-APs.

Rationale and design of the Web-basEd soCial media tecHnology to improvement in Adherence to dual anTiplatelet Therapy following Drug-Eluting Stent Implantation (WECHAT): protocol for a randomised controlled study.

BACKGROUND: Dual antiplatelet therapy (DAPT) is frequently discontinued after drug-eluting stent (DES) implantation, which could increase the risk of major adverse cardiovascular events (MACEs). Few studies have attempted to improve DAPT adherence through web-based social media. OBJECTIVE: To explore the effect of social media on DAPT adherence following DES implantation. METHODS/DESIGN: The WeChat trial is a multicentre, single-blind, randomised study (1:1). It will recruit 760 patients with DES who require 12 months of DAPT. The control group will only receive usual care and general educational messages on medical knowledge. The intervention group will receive a personalised intervention, including interactive responses and medication and follow-up reminders beyond the general educational messages. The primary endpoint will be the discontinuation rate which is defined as the cessation of any dual antiplatelet drug owing to the participants' discretion within 1 year of DES implantation. The secondary endpoints will include medication adherence and MACEs. Both groups will receive messages or reminders four times a week with follow-ups over 12 months. ETHICS AND DISSEMINATION: Ethical approval was granted by Ethics Committee of Guangdong Provincial People's Hospital (GDREC2018327H). Results will be disseminated via peer-reviewed publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT03732066.