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Rationale Long-acting injectable antipsychotic therapies may offer benefits over oral antipsychotics in patients with schizophrenia. Objective This study aimed to explore the safety, tolerability, and treatment response of paliperidone palmitate once-monthly in non-acute but symptomatic adult patients switched from previously unsuccessful monotherapy with frequently used oral atypical antipsychotics. Methods This was a post hoc analysis of a prospective, interventional, single-arm, international, multicenter, open-label, 6-month study. Results The patients (N = 472) were switched to paliperidone palmitate once-monthly (PP1M) from daily oral treatment with either aripiprazole (n = 46), olanzapine (n = 87), paliperidone extended-release (n = 104), quetiapine (n = 44), or risperidone (n = 191). In all groups, mean Positive and Negative Syndrome Scale total (p

Objective: To explore the treatment response, tolerability and safety of once-monthly paliperidone palmitate (PP1M) in non-acute patients switched from oral antipsychotics, stratified by time since diagnosis as recently diagnosed (≤3 years) or chronic patients (>3 years). Research design and methods: Post hoc analysis of a prospective, interventional, single-arm, multicentre, open-label, 6-month study performed in 233 recently diagnosed and 360 chronic patients. Main outcome measures: The proportion achieving treatment response (defined as ≥20% improvement in Positive and Negative Syndrome Scale [PANSS] total score from baseline to endpoint) and maintained efficacy (defined as non-inferiority in the change in PANSS total score at endpoint [Schuirmann’s test]). Results: 71.4% of recently diagnosed and 59.2% of chronic patients showed a ≥20% decrease in PANSS total score (p = 0.0028 between groups). Changes in PANSS Marder factors, PANSS subscales, and the proportion of patients with a Personal and Social Performance scale (PSP) total score of 71–100 were significantly greater in recently diagnosed compared with chronic patients. PP1M was well tolerated, presenting no unexpected safety findings. Conclusion: These data show that recently diagnosed patients treated with PP1M had a significantly higher treatment response and improved functioning, as assessed by the PSP total score, than chronic patients.

PALMFlexS, a prospective multicentre, open-label, 6-month, phase IIIb interventional study, explored tolerability, safety and treatment response in adults ( n = 231) with non-acute but symptomatic schizophrenia switching to flexibly dosed paliperidone palmitate (PP) after unsuccessful treatment with risperidone long-acting injectable therapy (RLAT) or conventional depot antipsychotics (APs). Treatment response was measured by change in Positive and Negative Syndrome Scale (PANSS) total score from baseline (BL) to last-observation-carried-forward (LOCF) endpoint (EP). Safety and tolerability assessments included Extrapyramidal Symptom Rating Scale (ESRS) total score and treatment-emergent adverse events. Significant reductions in mean PANSS total score were observed for all groups (−7.5 to −10.6; p ⩽ 0.01 [BL to LOCF EP]). After switching to PP, more than 50% of all patients achieved ⩾20% and one-third of RLAT-treated patients even achieved ⩾50% improvement in PANSS total score. Across groups, there were significant improvements ( p < 0.05) in symptom severity as measured by Clinical Global Impression-Severity (CGI-S; trend for improvement with RLAT; p = 0.0568), subjective well-being, medication satisfaction, and patient functioning with PP. PP was generally well tolerated. Clinically relevant benefits were observed in non-acute patients with schizophrenia switched from RLAT or conventional depot APs to PP.

The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4-infected patients with METAVIR F0-F4 fibrosis. Sixty-three patients (33 treatment-naive and 30 peg-interferon/ribavirin (Peg-IFN/RBV)-experienced) enrolled in a partly randomized, open-label, multicentre, phase IIa study. Patients with F0-F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82-97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg-IFN/RBV null responders. The most commonly reported treatment-emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4-infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight- and 12-week regimens.

SummaryAims There is a large population of people with type 2 diabetes mellitus (T2DM) who are Muslim and fast during Ramadan. Changes in the pattern and amount of meal and fluid intake during Ramadan, in addition to the long fasting hours, may increase the risk of hypoglycaemia, hyperglycaemia, and dehydration. The Canagliflozin in Ramadan Tolerance Observational Study (CRATOS) evaluated the tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, compared with sulphonylureas among patients with T2DM who fast during Ramadan. Methods This non-randomised, parallel-cohort, prospective, comparative, observational study was conducted in the Middle East during Ramadan and enrolled patients who were taking canagliflozin (n=162) or any sulphonylurea (n=159) added to metformin±dipeptidyl peptidase-4 inhibitor. The proportion of patients who experienced hypoglycaemia events was assessed as the primary end-point. Between-cohort comparisons were adjusted using propensity score analysis. Results During Ramadan, fewer patients experienced symptomatic hypoglycaemia with canagliflozin vs sulphonylurea (adjusted odds ratio: 0.273 [95% CI: 0.104, 0.719]). Of hypoglycaemia events for which blood glucose was measured, two of six with canagliflozin and 27 of 37 with sulphonylurea were confirmed by blood glucose

Background As illustrated by the Montreal classification, gastroesophageal reflux disease (GERD) is much more than heartburn and patients constitute a heterogeneous group. Understanding if links exist between patients’ characteristics and GERD symptoms, and classify subjects based on symptom-profile could help to better understand, diagnose, and treat GERD. The aim of this study was to identify distinct classes of GERD patients according to symptom profiles, using a specific statistical tool: Latent class analysis. Methods An observational single-visit study was conducted in 5 European countries in 7700 adults with typical symptoms. A latent class analysis was performed to identify “latent classes” and was applied to 12 indicator symptoms. Results On 7434 subjects with non-missing indicators, latent class analysis yielded 5 latent classes. Class 1 grouped the highest severity of typical GERD symptoms during day and night, more digestive and non-digestive GERD symptoms, and bad sleep quality. Class 3 represented less frequent and less severe digestive and non-digestive GERD symptoms, and better sleep quality than in class 1. In class 2, only typical GERD symptoms at night occurred. Classes 4 and 5 represented daytime and nighttime regurgitation. In class 4, heartburn was also identified and more atypical digestive symptoms. Multinomial logistic regression showed that country, age, sex, smoking, alcohol use, low-fat diet, waist circumference, recent weight gain (>5 kg), elevated triglycerides, metabolic syndrome, and medical GERD treatment had a significant effect on latent classes. Conclusion Latent class analysis classified GERD patients based on symptom profiles which related to patients’ characteristics. Although further studies considering these proposed classes have to be conducted to determine the reproducibility of this classification, this new tool might contribute in better management and follow-up of patients with GERD.

PurposeThe goal of this study was to explore the tolerability, safety, and treatment response of flexible doses of once-monthly paliperidone palmitate (PP) in the subset of nonacute but symptomatic adult patients with schizophrenia previously unsuccessfully treated with oral antipsychotic agents in the PALMFlexS (Paliperidone Palmitate Flexible Dosing in Schizophrenia) study.MethodsThis was an interventional, single-arm, international, multicenter, unblinded, 6-month study performed in patients with schizophrenia. Patients were categorized according to reasons for switching. In patients switching because of lack of efficacy or for other reasons, primary efficacy outcomes were the proportion achieving treatment response (defined as ≥20% improvement in Positive and Negative Syndrome Scale [PANSS] total score from baseline to last-observation-carried-forward end point) and maintained efficacy (defined as noninferiority in the change in PANSS total score at end point versus baseline [Schuirmann’s test]), respectively.FindingsA total of 593 patients (intention-to-treat population) were enrolled: 63.1% were male; their mean (SD) age was 38.4 (11.8) years; and 78.6% had paranoid schizophrenia. The main reasons for transition to PP were patient’s wish (n = 259 [43.7%]), lack of efficacy (n = 144 [24.3%]), lack of compliance (n = 138 [23.3%]), and lack of tolerability (n = 52 [8.8%]) with the previous oral antipsychotic medication. The recommended PP initiation regimen (150 milligram equivalents [mg eq] day 1 and 100 mg eq day 8) was administered in 93.9% of patients. Mean PANSS total score decreased from 71.5 (14.6) at baseline to 59.7 (18.1) at end point (mean change, –11.7 [15.9]; 95% CI, –13.0 to –10.5; P < 0.0001). Sixty-four percent of patients showed an improvement of ≥20% in PANSS total score, and the percentage of patients rated mildly ill or less in Clinical Global Impression–Severity increased from 31.8% to 63.2%. Mean personal and social performance total score (SD) increased (ie, improved) significantly for all patients from baseline to end point (58.1 [13.4] to 66.1 [15.7]; P < 0.0001).ImplicationsThe PALMFlexS study is a pragmatic interventional study compared with randomized controlled trials, conducted in a large, more representative sample of patients with schizophrenia, and designed specifically to mimic real-world clinical situations. The findings support the results from randomized controlled studies. They also demonstrate that a clinically relevant treatment response is possible in patients who are considered to be clinically stable by their physician, supporting the use of flexibly dosed PP in such patients. Clinical trials.gov number: NCT01281527.