Main Reason For Discontinuation Research Articles

An observational study to test the acceptability and feasibility of using medical and nursing students to instruct clients in DMPA-SC self-injection at the community level in Kinshasa

ObjectivesGiven the promise of DMPA-SC to increase community-level access to modern contraception in developing countries, we conducted an observational study to assess the acceptability and feasibility of DMPA-SC self-injection among women in Kinshasa, Democratic Republic of the Congo, and of medical/nursing (M/N) students as instructors for self-injection. Study designWomen who selected DMPA-SC at a community outreach event adjacent to a health center were interviewed upon acceptance (baseline) and then 3, 6 and 12 months later. ResultsOf 850 clients selecting DMPA-SC at baseline, 640 (75.3%) opted for self-injection over being injected by the M/N students for reasons of convenience and personal agency. Among these 640 self-injectors, 47.5% were anxious at baseline (for fear of needles or injecting incorrectly). Over 80% reported feeling very ready after training, confident that they knew how to self-inject and confident that they would remember the next injection date. By 3 months, 97% described it as easy. Half (54%) experienced side effects, mainly menstrual irregularities, the main reason for discontinuation. At 6-month follow-up, self-injectors cited effectiveness and ease of use as positive elements, though one quarter reported side effects. Their impressions of M/N students as instructors were highly positive. ConclusionsWhere DMPA-SC was free and easily accessible, the majority of women interested in DMPA-SC opted to learn self-injection. The M/N students performed well in instructing women to self-inject. Clients were highly satisfied with the services received, yet many did not recognize their student status, possibly because outreach occurred near a health facility. Once told, clients remained very favorable, suggesting strong motivation to receive their preferred contraceptive free, whoever the provider. Implication statementThis study provides additional evidence on the acceptability and the feasibility of the self-injection of DMPA-SC by users from a resource-limited setting.

Patterns of Dietary Supplement Use in Children with Down Syndrome

To determine the frequency of dietary supplement use for children with Down syndrome, and to obtain additional descriptive data regarding the age of initial treatment, cost, perceived benefits, and disclosure of use to the pediatrician. An anonymous questionnaire in English and Spanish was created for parents of children under age 18 years with Down syndrome. Surveys were completed in our clinic, or accessed on a number of Down syndrome-related websites. A total of 1167 responses were completed and analyzed. Forty nine percent of responders currently/previously gave their child supplement(s). The average child received 3 supplements (ranging from 1-18). Although Nutrivene, curcumin, and green tea extract were most common, over 150 different products were reported. Supplementation began most often in infancy, generally between age 4 and 6 months. Average cost was $90.53/month. Overall, 87% of users noted improvement, mainly in speech, immunity, and attention; 17% reported side-effects, predominantly gastrointestinal disturbance. Lack of improvement and cost were the main reasons for discontinuation. Most parents learned of supplements through a parent group or friend. In almost 20%, the pediatrician was unaware of the supplement use. Almost one-half of parents surveyed administer or have administered supplement(s) to their children with Down syndrome. Many of the supplements have concerning ingredient profiles and are given to children too young to articulate potential ill effects. Providers need to be aware of these products and question families about their use.

Reasons and predictors of discontinuation of running after a running program for novice runners

ObjectivesTo determine the proportion of participants of a running program for novice runners that discontinued running and investigate the main reasons to discontinue and characteristics associated with discontinuation. DesignProspective cohort study. MethodsThe study included 774 participants of Start to Run, a 6-week running program for novice runners. Before the start of the program, participants filled-in a baseline questionnaire to collect information on demographics, physical activity and perceived health. The 26-weeks follow-up questionnaire was used to obtain information on the continuation of running (yes/no) and main reasons for discontinuation. To determine predictors for discontinuation of running, multivariable logistic regression was performed. ResultsWithin 26 weeks after the start of the 6-week running program, 29.5% of the novice runners (n=225) had stopped running. The main reason for discontinuation was a running-related injury (n=108, 48%). Being female (OR 1.74; 95% CI 1.13–2.68), being unsure about the continuation of running after the program (OR 2.06; 95% CI 1.31–3.24) and (almost) no alcohol use (OR 1.62; 95%CI 1.11–2.37) were associated with a higher chance of discontinuation of running. Previous running experience less than one year previously (OR 0.46; 95% CI 0.26–0.83) and a higher score on the RAND-36 subscale physical functioning (OR 0.98; 95% CI 0.96–0.99) were associated with a lower chance of discontinuation. ConclusionsIn this group of novice runners, almost one-third stopped running within six months. A running-related injury was the main reason to stop running. Women with a low perceived physical functioning and without running experience were prone to discontinue running.

Tolerability and efficacy of deferasirox in patients with transfusional iron overload: results from a German 2-year non-interventional study.

Iron overload (IOL) due to repetitive transfusions of packed red blood cells (pRBC) has a major impact on morbidity and mortality in patients with inherited bone marrow failure syndromes and hemoglobinopathies such as thalassemia and sickle cell disease. However, whether IOL influences the outcome of elderly patients with myeloid malignancies is not yet clear. Moreover, clinical trials have reported high drop-out rates during treatment with the oral iron chelator deferasirox (DFX). Here we report the results of a 2-year prospective observational study that aimed at describing the routine use of DFX in patients with hematological malignancies with regard to safety, efficacy and handling of the drug in a routine setting. A total of 406 patients were included. 58% of the patients were male. Most of the patients had myelodysplastic syndromes (MDS) (68%) and myeloproliferative neoplasms (MPN) (14%). Median time from first transfusion to study enrollment was 1.1 years (0-25.5 years) and most patients were chelation naive (91%) at enrollment. With regard to transfusion burden, most of the patients were moderately or mildly transfusion-dependent with 53% receiving 2-4 and 27% receiving less than 2 units of pRBC per month. Serum ferritin decreased from a mean of 2305 μg/l (± 1449 μg/l) to a mean of 1910 μg/l (± 1529 μg/l) at 24 months. There was no substantial change in transfusion-dependence during the observation period. Dose adjustments were reported in 48% of the patients with dose-escalation strategies being the most frequent reason for dosage increases (49%). The median observation time was 355days (5-1080days). Median duration of exposure to DFX was 322days (2-1078days). Two-hundred and ninety (72%) patients discontinued the trial prematurely after a median time of 235days (1-808days). Death (29%) and adverse events (23%) were the main reasons for discontinuation. Eleven percent of the patients discontinued treatment due to sufficient decrease in serum ferritin. Most frequent adverse events were decrease in creatinine clearance (22%), increase in serum creatinine (18%) and diarrhea (16%). This descriptive trial confirms the efficacy of DFX in decreasing the serum ferritin. Moreover, the high drop-out rates seen in prospective trials are recapitulated in this study, which can be attributed to adverse events in a substantial proportion of patients.

Real world treatment patterns of first-line combination therapies among BRAF+ metastatic melanoma patients stratified by tumor burden.

198 Background: For patients (pts) with metastatic melanoma (MM) and BRAF V600 mutation (BRAF+), options for first-line (1L) systemic combination therapy include immunotherapy (IO) or targeted therapy (TT). This study describes real world treatment patterns among BRAF+ MM pts treated with 1L ipilimumab+nivolumab (I+N) or dabrafenib+trametinib (D+T), stratified by tumor burden. Methods: A retrospective observational analysis used Flatiron Health’s electronic health record-derived database from Oct ’15 - Jul ’16. Pts were aged ≥18 years with a MM diagnosis, tested BRAF+ prior to therapy, and treated with ipilimumab+nivolumab (I+N) or dabrafenib+trametinib (D+T) as 1L therapy. Low tumor burden was defined as low/normal LDH (≤ 333 IU/L) and no brain metastasis. High tumor burden was defined as high LDH ( > 333 IU/L) or brain metastasis. Baseline characteristics and treatment patterns were descriptively assessed. Kaplan-Meier (KM) analysis measured time to discontinuation. Results: Among 76 BRAF+ pts, 38% (29) were treated with I+N as 1L, and 62% (47) were treated with D+T as 1L. Of these, 45% (13/29) of I+N vs. 32% (15/47) of D+T had low tumor burden, while 41% (12/29) of I+N vs. 49% (23/47) of D+T had high tumor burden. The two cohorts did not differ by age or gender. Treatment patterns are summarized below. Conclusions: Among pts with low tumor burden, I+N demonstrated shorter time to discontinuation and higher discontinuation rate relative to D+T. Treatment toxicity and progression was the main reason for discontinuation of I+N and D+T, respectively. Among pts with high tumor burden, I+N demonstrated longer time to discontinuation but higher discontinuation rate relative to D+T. Progression was the main reason for discontinuation of both I+N and D+T. [Table: see text]

A prospective year-long follow-up of lurasidone use in clinical practice: factors predicting treatment persistence.

Background:Our aim was to follow up patients prescribed lurasidone over 1 year to determine factors predicting treatment persistence.Methods:We used noninterventional, observational, prospective follow up of patients consecutively prescribed lurasidone in a large inner-city NHS mental health trust. We also performed retrospective analysis of outcomes from patient case notes.Results:Data were available for 69 patients consecutively prescribed lurasidone, of whom three (4%) were lost to follow up. Out of the 66 patients not lost to follow-up, 21 (32%) remained on lurasidone at 1 year. The main reasons for discontinuation were perceived ineffectiveness (49% of discontinuers) and adverse effects (36% of discontinuers), whilst a further seven refused all treatment. Median treatment time on lurasidone was 154 days (95% confidence interval (CI), 33–275). Patients who were not treatment-resistant had a substantially reduced risk of discontinuation, relative risk (RR) 0.18 [95% CI 0.08, 0.41, p < 0.001]. Medium doses (>37–74 mg) of lurasidone reduced the risk of discontinuation by 75% [RR 0.25 (95% CI 0.11, 0.58, p = 0.001)]; high doses (>74–148 mg) reduced the risk of discontinuation by 86% [RR 0.14 (95% CI 0.06, 0.35, p < 0.001)]. Risk of discontinuation was approximately doubled when the reason for prescribing lurasidone was poor tolerability of prior treatment [RR 2.01 (95% CI 1.05, 3.85, p = 0.035)].Conclusion:The likelihood of treatment continuation with lurasidone can be vastly improved by targeting individuals most likely to benefit and by using optimal doses.

Clozapine discontinuation in early schizophrenia: a retrospective case note review of patients under an early intervention service.

Aim:Research in patients with treatment-resistant schizophrenia has demonstrated that clozapine discontinuation is associated with poor outcomes. There is, however, a paucity of research investigating the impact of clozapine discontinuation specifically in younger patients with more recent onset schizophrenia. A case note review was therefore conducted to ascertain medium-term prognoses in patients with treatment-resistant schizophrenia under an early intervention service (EIS) following clozapine discontinuation.Methods:The case notes of 25 patients under the care of Birmingham EIS who discontinued clozapine were examined retrospectively. Reasons for discontinuation were recorded. Clinical outcomes including total duration of inpatient or home treatment admission, antipsychotic dose, number of alternative antipsychotics prescribed and adverse events were recorded for both the year before and the year after stopping clozapine. Statistical comparisons of pre- and post-discontinuation clinical outcomes determined whether discontinuation had negative effects.Results:There was no significant difference between the pre- and post-discontinuation clinical status following clozapine discontinuation. More than half (56%) of patients remained stable after stopping clozapine. Mean inpatient or home treatment stay rose from 29.7 to 62.6 days (p = 0.155), total antipsychotic dose from 50.1% of British National Formulary (BNF) limits to 60.5% (p = 0.627), number of alternative antipsychotics prescribed from 1.28 to 1.80 (p = 0.186), number of hospital/home treatment episodes from 0.20 to 0.44 (p = 0.083) and number of adverse events from 0 to 0.20 (p = 0.059). Non-compliance was the main reason for discontinuation (44%, n = 11).Conclusions:This is the first clozapine discontinuation study specifically considering EIS patients. Discontinuation did not lead to significant effects on 1 year outcomes, though the study is underpowered. These findings may be used to inform future prospective cohort discontinuation studies.

Four-year long-term follow-up of diabetes patients after implementation of the Chronic Care Model in primary care: a cross-sectional study.

Implementing the Chronic Care Model (CCM) via involvement of specially trained practice nurses improves cardiovascular risk profiles and perception of care among type 2 diabetes patients in small primary care practices (PCPs) in the short term. Little is known about the long-term effects of this intervention. Cross-sectional survey among the participants of the cluster randomised controlled CARAT trial (30 PCPs, 303 diabetes patients), 3 years after its completion. Proportion of patients still treated according to the CCM, possible reasons for discontinuation, glycosylated haemoglobin (HbA1c), blood pressure, low density lipoprotein cholesterol, and accordance with CCM (assessed by means of PACIC [Patient Assessment of Chronic Illness Care]). Overall, 40.9% of practices (40.7% of patients) continued using the CCM. PCPs originally randomised to the intervention group were significantly more likely to be still using the CCM (11 PCPs / 88 patients vs 11 PCPs / 94 patients, p <0.001). Main reasons for discontinuation were organisational (40.9%) and financial aspects (18.1%), and the general practitioner refusing to transfer treatment responsibility (18.1%). HbA1c and PACIC development over the long term showed significant positive effects in favour of PCPs originally randomised to the intervention group and practices continuing to treat patients according to the CCM. Diabetes care according to the CCM, including the involvement of trained practice nurses, is a reasonable tool to improve care in the long-term. CCM training of the whole team is essential to overcome organisational challenges. Continuous team education, technical decision support, and recognition of the importance of these new structures in healthcare policy might improve the long-term clinical effect of the team approach.

Pregnancy outcomes associated with extended use of the 52-mg 20 μg/day levonorgestrel-releasing intrauterine system beyond 60 months: A chart review of 776 women in Brazil

ObjectiveTo assess the contraceptive performance of the 52-mg 20 μg/day levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena; Bayer Oy, Turku, Finland) among women who maintain the same device without changes after 60 months. Study designThis is a chart review study in which we assessed the charts of 766 women who continue the same LNG-IUS for contraception beyond 60 months. The women were evaluated at the Family Planning clinic, University of Campinas Medical School, Campinas, SP, Brazil, from November 1990 to March 2011. We obtained sociodemographic data, duration of use, continuation and discontinuation rates and reasons, bleeding pattern at the recorded last visit. The statistical analysis was performed using Kaplan–Meier analysis. ResultsA total of 776 charts were identified of women who used the LNG-IUS beyond 60 months. The mean age (±S.E.M.) at LNG-IUS placement was 32.0±0.2 years (ranged 15 to 44 years; median was 32 years). The distribution of number of pregnancies was 0–1 (45%); 2–4 (54.1%) and≥5 (0.9%). The median length of the LNG-IUS' use was 73 months after placement (ranged 61–184 months). Zero pregnancies were reported and the main reasons for discontinuation were expiration of approved effective lifespan, menopause and planning pregnancy. The cumulative women-years (W-Y) of exposure were 967 and 1403 up to seven and 15 years, respectively. The main bleeding pattern reported by the women was amenorrhea. ConclusionsThe 52-mg 20 μg/day LNG-IUD (Mirena) showed continue contraceptive efficacy beyond 5 years of use with no pregnancies detected over 967 and 1403 W-Y up to seven and 15 years after placement. Implications statementThe 52-mg 20 μg/day LNG-IUD presented a very high contraceptive efficacy beyond the first 5 years of lifetime labeled. Increasing data support that efficacy beyond 5 years of use, and new data suggested efficacy as long as 15 years. Healthcare professionals, policy makers and stakeholders could take advantage of the present information to decide to maintain the same device at least up to seven years. Furthermore, amenorrhea could be a good indicator of contraceptive effect.

Discontinuation of Dapoxetine Treatment in Patients With Premature Ejaculation: A 2-Year Prospective Observational Study.

IntroductionAlthough dapoxetine is the only oral pharmacologic agent approved for the treatment of premature ejaculation (PE) and is very effective, the discontinuation rate is high.AimTo assess the discontinuation rate of patients with PE and the reasons for discontinuation in real-world practice.MethodsIn total, 182 consecutive patients were enrolled. Type of PE, self-estimated intravaginal ejaculation latency time, and medical history were evaluated in all patients who also completed the erectile function domain of the International Index of Erectile Function (IIEF). Visits were scheduled 1, 3, 6, 12, and 24 months after initiation of therapy; treatment status and the reasons for discontinuation in those who did discontinue were checked. The relations of discontinuation rates were compared with various parameters and the time to discontinuation after treatment commencement.ResultsOf all patients, 9.9% continued treatment to 2 years. The cumulative discontinuation rates at 1, 3, 6, 12, and 24 months were 26.4%, 61.6%, 79.1%, 87.3%, and 90.1%, respectively. Moreover, 79.1% of all patients discontinued treatment within 6 months. After 12 months, the discontinuation rate decreased sharply. The reasons for discontinuation were cost (29.9%), disappointment that PE was not curable and that dapoxetine was required every time sexual intercourse was contemplated (25%), side effects (11.6%), perceived poor efficacy (9.8%), a search for other treatment options (5.5%), and unknown (18.3%). Patients with acquired PE (vs lifelong PE), with intravaginal ejaculation latency time longer than 2 minutes before treatment, on phosphodiesterase type 5 inhibitors, and with IIEF erectile function scores lower than 26 tended to discontinue early and thus exhibited high dropout rates.ConclusionThe treatment discontinuation rate of dapoxetine was very high. The main reasons for discontinuation were the cost and disappointment that treatment was required every time adequate sexual function was required.Park HJ, Park NC, Kim TN, et al. Discontinuation of Dapoxetine Treatment in Patients With Premature Ejaculation: A 2-Year Prospective Observational Study. Sex Med 2017;5:e99–e105.

Continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease: 10-year experience with 230 patients

Continuous apomorphine infusion (APO) is one of the treatments available for advanced Parkinson disease (PD). Over 10years, we have treated 230 patients with APO. Mean age was 66.8 and average evolution time at APO onset was 13.0years. Mean duration of the treatment was 26.3months. As of June 2016, 93 remained on the medication (active group), while 137 had stopped. This active group had mean age 67.3 at recruitment and mean evolution 14.2years. The main indication for APO was lack of deep brain stimulation criteria (DBS). Twelve patients were on waiting list for DBS. Average time since APO onset was 40.0months. In the active group, APO decreased off-state in 4h and allowed reducing levodopa and dopamine agonists. Dyskinesia and balance did not worsen. Cognitive decline did not change within the first 15months. Hallucinations were the same within the first 39months. The presence of subcutaneous nodules was the most frequent adverse event in this group. The main reason for discontinuation was side effects, being psychosis the most common. Within the first year, 82 patients stopped APO. Eighteen of these patients eventually got DBS. APO is a good option for advanced PD, since it permits a significant reduction in off-time and other antiparkinsonian drugs. This effect is sustained over time. We have treated 132 patients for over a year. Dyskinesia seems not to worsen. Combining APO with DBS simultaneously or alternatively provides good results.

Real-life experience with brivaracetam in 101 patients with difficult-to-treat epilepsy—A monocenter survey

PurposeTo assess the efficiency of brivaracetam under real-world conditions in a tertiary referral epilepsy center. MethodsWe consecutively collected patients treated at our center with brivaracetam (BRV). After a minimum observation period of six months we retrospectively analyzed the efficiency of BRV. ResultsData of 101 patients (mean age 42 years, range 18–81 years, 54 females,) were analyzed. The median number of antiepileptic drugs (AEDs) used prior to BRV was 10 (range 2–18). The initial dose of BRV was at least 50mg per day, the mean maintenance dose at cut-off was 168.6mg (median 200mg, range 50–400mg).Efficacy data were assessed for the last three months or at the time of the last observation carried forward if BRV had been discontinued prematurely. Responder rate was 27.8% (n=28) with 7% seizure-free patients. Adverse events (AEs) occurred in 37 patients (37%). Most frequent AEs were dizziness (16%) and somnolence (11%). Psychiatric adverse events comprised irritability, aggression, depression and psychosis in single cases. Retention rate after six months was 51.5%. Main reason for discontinuation was a lack of efficacy.In 43 cases LEV and BRV were switched. The switch was performed abruptly without complications. In 26 cases (60%) BRV was discontinued and re-switched to LEV within weeks, mainly due to a lack of better efficacy. After the switch from LEV to BRV we even saw an aggravation both of seizure frequency and severity in 5 cases. Retention rate in patients who had not been on LEV was 57%. ConclusionIn our hands BRV appeared to be well tolerated and easy to handle. The retention rate was influenced by patients who were switched from LEV and re-switched because BRV was not more efficient. Switching from and re-switching to LEV was easy.

Premature clinical trial discontinuation in all and genitourinary (GU) cancers in the era of immune checkpoint inhibitors (ICI).

394 Background: Clinical trial completion is critical for evaluating new therapies. Premature termination or withdrawal of clinical trials is common, impairs progress and results in waste of resources. We assessed features and reasons of early terminated and withdrawn cancer trials focusing on trials with ICI (anti-CTLA-4, anti-PD-1, anti-PD-L1). Methods: We reviewed all adult, intervention, cancer clinical trials registered in ClinicalTrials.gov from November 16, 2011 to April 16, 2015 to identify all early terminated and withdrawn trials. Reasons for termination were captured. Logistics regression model was used to identify factors associated with early termination or withdrawal. Discontinuation rate was compared between ICI and all trials (χ2); p &lt; 0.05 was set as significant. Results: We identified 12875 clinical trials (35% industry-funded, 12% federal-funded; 772 in prostate and 386 in non-prostate GU cancers); 8.5% of all trials were prematurely terminated (5%) or withdrawn (3.5%); main reason for discontinuation was poor accrual (33%) followed by logistical reasons (26%). When comparing trials with ICI (n = 350) to all cancer trials, lower rate of termination or withdrawal was noted with ICI [5.4% vs 8.5%, p = 0.05]. Trials with ICI were less likely to discontinue due to poor accrual compared to all trials, but the difference was not significant (21% vs 33%, p = 0.4). Of the 1158 GU cancers trials, 75 (6.5%) were prematurely terminated and 56 (4.8%) withdrawn; reasons for discontinuation are shown in the table. Conclusions: Poor accrual represents the main cause of early termination of all cancer clinical trials. Premature termination/withdrawal rate appears lower in ICI trials which may be attributed to accrual differences. Clinical trial completion remains a high priority. [Table: see text]

Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial

Despite a broad range of pharmacological options for the treatment of type 2 diabetes, optimum glycaemic control remains challenging for many patients and new therapies are necessary. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue in phase 3 development for type 2 diabetes. We assessed the efficacy, safety, and tolerability of semaglutide monotherapy, compared with placebo, in treatment-naive patients with type 2 diabetes who had insufficient glycaemic control with diet and exercise alone. We did a double-blind, randomised, parallel-group, international, placebo-controlled phase 3a trial (SUSTAIN 1) at 72 sites in Canada, Italy, Japan, Mexico, Russia, South Africa, UK, and USA (including hospitals, clinical research units, and private offices). Eligible participants were treatment-naive individuals aged 18 years or older with type 2 diabetes treated with only diet and exercise alone for at least 30 days before screening, with a baseline HbA1c of 7·0%-10·0% (53-86 mmol/mol). We randomly assigned participants (2:2:1:1) to either once-weekly subcutaneously injected semaglutide (0·5 mg or 1·0 mg), or volume-matched placebo (0·5 mg or 1·0 mg), for 30 weeks via prefilled PDS290 pen-injectors. Participants did their own injections and were encouraged to administer them on the same day of each week in the same area of their body; the time of day and proximity of meal times was not specified. We did the randomisation with an interactive voice or web response system. Investigators, participants, and the funder of the study remained masked throughout the trial. The primary endpoint was the change in mean HbA1c from baseline to week 30, and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30. We assessed efficacy and safety in the modified intention-to-treat population (ie, all participants who were exposed to at least one dose of study drug); both placebo groups were pooled for assessment. This trial was registered with ClinicalTrials.gov, number NCT02054897. Between February 3, 2014, and August 21, 2014, we randomly assigned 388 participants to treatment; 387 received at least one dose of study medication (128 0·5 mg semaglutide, 130 1·0 mg semaglutide, 129 placebo). 17 (13%) of those assigned to 0·5 mg semaglutide, 16 (12%) assigned to 1·0 mg semaglutide, and 14 (11%) assigned to placebo discontinued treatment; the main reason for discontinuation was gastrointestinal adverse events such as nausea. Mean baseline HbA1c was 8·05% (SD 0·85); at week 30, HbA1c significantly decreased by 1·45% (95% CI -1·65 to -1·26) with 0·5 mg semaglutide (estimated treatment difference vs placebo -1·43%, 95% CI -1·71 to -1·15; p<0·0001), significantly decreased by 1·55% (-1·74 to -1·36) with 1·0 mg semaglutide (estimated treatment difference vs placebo -1·53%, -1·81 to -1·25; p<0·0001), and non-significantly decreased by 0·02% (-0·23 to 0·18) with placebo. Mean baseline bodyweight was 91·93 kg (SD 23·83); at week 30, bodyweight significantly decreased by 3·73 kg (95% CI -4·54 to -2·91) with 0·5 mg semaglutide (estimated treatment difference vs placebo -2·75 kg, 95% CI -3·92 to -1·58; p<0·0001), significantly decreased by 4·53 kg (-5·34 to -3·72) with 1·0 mg semaglutide (estimated treatment difference vs placebo -3·56 kg, -4·74 to -2·38; p<0·0001), and non-significantly decreased by 0·98 kg (-1·82 to -0·13) with placebo. No deaths were reported in any of the study groups and most reported adverse events were of mild or moderate severity. The most frequently reported adverse events in both semaglutide groups were gastrointestinal in nature: nausea was reported in 26 (20%) who received 0·5 mg semaglutide, 31 (24%) who received 1·0 mg semaglutide, and 10 (8%) who received placebo, and diarrhoea was reported in 16 (13%) who received 0·5 mg semaglutide, 14 (11%) who received 1·0 mg semaglutide, and three (2%) who received placebo. Semaglutide significantly improved HbA1c and bodyweight in patients with type 2 diabetes compared with placebo, and showed a similar safety profile to currently available GLP-1 receptor agonists, representing a potential treatment option for such patients. Novo Nordisk A/S, Denmark.

Hormone replacement therapy use in UK general practice: Duration, discontinuation and women’s experience

Objective Investigate characteristics of women treated with combined estrogen and progestogen hormone replacement therapy (study-HRT); HRT patterns; reasons and outcomes associated with HRT discontinuation. Study design Retrospective observational study using The Health Improvement Network database examining women’s characteristics and treatment patterns (Database). Postal questionnaire exploring reasons and outcomes associated with HRT discontinuation (Survey). Main outcome measures Database: Demographic and clinical characteristics. HRT patterns, time from diagnosis to treatment, duration of treatment, type of treatment and change of treatment (switch, add-on, re-start and discontinuation). Survey: HRT therapy status, menopause rating scale and reasons for discontinuation. Results Database: 8968 women prescribed study-HRT between January 2006 and January 2010 were matched 1:1 on GP practice and age with women not prescribed HRT. Women prescribed study-HRT were more likely to be a current/past smoker ( p&lt;0.05) and experienced higher levels of co-morbidities related to menopause ( p &lt; 0.05) versus women not prescribed HRT. Treatment duration was approximately 14 months and 95% changed treatment during the study. Survey: 116 respondents. Women on HRT had lower MRS scores ( p &lt; 0.05) than women who discontinued HRT. Main reasons for discontinuation were medical advice, side-effects/potential side-effects. Fear of breast cancer was also stated as a reason. Conclusions Duration of HRT was relatively short, with 95% of women changing treatment. HRT discontinuation was associated with more severe menopause symptoms. Medical advice and concerns about side-effects were major reasons for the discontinuation, suggesting that there was a need for a balanced dialogue with women about risks and benefits of HRT, as emphasised by NICE guidance.

Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis.

Few reported studies compare drug survival in moderate-to-severe psoriasis vulgaris. To describe and compare drug survival of systemic drugs, including biologic agents (infliximab, etanercept, adalimumab and ustekinumab) and classical drugs (acitretin, ciclosporin and methotrexate) in moderate-to-severe psoriasis. This was a multicenter, prospective, cohort study of patients receiving systemic therapies between 2008 and 2013 in 12 hospitals in Spain. Baseline data and drug discontinuation were collected. Drug survival is presented using Kaplan-Meier survival curves. We compared adjusted risk ratios of serious adverse events (AEs) with results of survival analysis for AEs. A total of 1956 patients were included for analysis (1240 exposed to biologics during follow-up and 1076 to classic therapies). Median follow-up time was 3.3 years (0.0-5.1 years). There were 2209 discontinuations out of 3640 therapy cycles started. The main reason for discontinuation was lack of efficacy (36.4%) and remission (27.2%). Biologics showed a higher drug survival than classics and the pattern of survival results for all outcomes (positive or negative) were very similar. Adjusted risk ratios of serious AEs did not agree with results of survival analysis. A limitation is that this is an observational study with potential selection bias. Survival as a proxy measure of drug safety in psoriasis is inadequate.

Discontinuation of Dapoxetine Treatment in Patients with Premature Ejaculation: A 2-Year Prospective Observational Study

Objective: Although dapoxetine is the only oral agent approved for premature ejaculation (PE) and is very effective, its discontinuation rate is high compared to PDE5 inhibitors for ED treatment. We assessed discontinuation rate of dapoxetine in PE and the reasons for discontinuation. Design and Method: The study enrolled 182 patients (mean age 38.2). The PE type (life-long or acquired), self-estimated intravaginal ejaculation latency time (IELT), IIEF-EF questionnaire, and medical history were checked in all patients. The patients were evaluated 1, 3, 6, 12, and 24 months after initiating therapy regarding the treatment status and the reasons for treatment discontinuation. Results: Of the patients, 9.9% were still in treatment after 2 years. The discontinuation rates at 1, 3, 6, 12, and 24 months were 26.4, 35.2, 17.6, 8.2, and 2.7%, respectively. Cumulatively, 79.1% of the patients discontinued the treatment within 6 months. After 12 months, however, the discontinuation rate dropped sharply. The reasons for discontinuation were cost (29.9%), disappointment that PE is not a curable disease and dapoxetine was needed whenever he had sex (25%), side effects (11.6%), low efficacy (9.8%), to seek other treatment options (5.5%), and unknown (18.3%). Patients with acquired PE (vs. life-long), IELT &gt;2 min before treatment, older than 50 years, taking PDE-5 inhibitors, and IIEF-EF &lt;26 tended to discontinue early and had high drop-out rates. Conclusions: Only 9.9% patients continued treatment after 24 months, while 79.1% discontinued within 6 months. The main reasons for discontinuation were not related to its side effects or low efficacy.

Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity

BackgroundThe approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients. The aim of our...

Alitretinoin and acitretin in severe chronic hand eczema; results from a retrospective daily practice study

Acitretin has been used off-label for years to treat chronic hand eczema, but acitretin is less often prescribed as alitretinoïne was approved. This study evaluates both retinoids in a daily practice cohort of patients with severe chronic hand eczema in terms of drug survival and reasons for discontinuation. Patients using alitretinoin or acitretin between 01-01-1994 and 01-08-2015 were included in this retrospective daily practice study and analyzed by Kaplan-Meier drug survival curves. Potential determinants were analyzed by Cox regression analyses. Ninety-five patients were treated with alitretinoin and 109 patients with acitretin. The main reasons for discontinuation were adverse events and cleared hand eczema, 29.5 and 27.4% in alitretinoin versus 43.1 and 23.9% in acitretin. Patients with hyperkeratotic hand eczema had most often a good effect of treatment: 68.3% in alitretinoin and 50.7% in acitretin treatment. The drug survival rates of alitretinoin and acitretin after 12, 24, 36, and 52 weeks were 69.3, 45.1, 19.6, 7.0% and 74.3, 45.5, 33.8, 23.2%, respectively. Alitretinoin and acitretin are effective treatment options for patients with hand eczema. However, both treatments were more effective in patients with hyperkeratotic hand eczema. Fewer patients discontinued alitretinoin compared with acitretin due to adverse events.

A retrospective comparison between regorafenib and TAS-102 for refractory metastatic colorectal cancer.

723 Background: Regorafenib (R) and TAS-102 (T) prolonged survival for patients (pts) with refractory metastatic colorectal cancer (mCRC) in phase 3 trials. However, little is known regarding optimal sequence of administration of R and T, because of lack of head-to-head trials. Methods: We retrospectively evaluated pts who had been treated with R or T in two institutions from May 2013 to March 2015. Inclusion criteria were ECOG PS 0–2, refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, angiogenesis inhibitors, and anti-EGFR antibodies (if KRAS wild type), and no previous treatment with R or T. Results: A total of 182 pts (R/T: 138/44) were eligible for the study. The baseline characteristics were similar for the two groups as follows (R/T): median age, 64/63.5; male, 61%/52%; and KRAS wild type, 52%/59%. However, the proportion of pts with ECOG PS 2 (8%/18%) and who had not received irinotecan (1%/14%) was lower in R than in T. Efficacies were as follows (R/T): response rate, 0.8%/0%; disease control rate, 34%/33%; median time to treatment failure, 1.8/1.9 months (m) (median duration of follow-up, 5.6/5.0 m); median progression-free survival (PFS), 2.1/2.0 m (HR 1.09, p= 0.62, adjusted HR 0.97, p= 0.89 [11 covariates such as age, PS, and KRAS status]); median survival time (MST), 5.9/5.8 m (HR 0.92, p= 0.70); and MST for 74 eligible pts (R/T: 30/44) after the approval of T in Japan, 6.4/5.8 m (HR 0.94, p= 0.84, median duration of follow-up 4.7/5.0 m). Subgroup analysis suggested that pts with higher age and poor PS had shorter PFS in R than in T. The frequency (R/T) of grade 3 or 4 hand–foot syndrome and increased ALT were higher in R than in T (21%/0% and 10%/0%). Conversely, the frequencies of grade 3 or 4 neutropenia, anemia, and febrile neutropenia were lower in R than in T (2%/34%, 8%/27%, and 0%/7%, respectively). The main reason for discontinuation was disease progression (R/T: 85%/82%). Subsequent chemotherapies were received in 53%/46% (R/T). Conclusions: Our retrospective analysis suggested that regorafenib and TAS-102 had similar efficacy in patients with refractory mCRC. Our study results indicate that different toxicity profiles should be considered when selecting a drug treatment.