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How can we improve the care of patients with schizophrenia in the real-world? A population-based cohort study of 456,003 patients

An important step to improve outcomes for patients with schizophrenia is to understand treatment patterns in routine practice. The aim of the current study was to describe the long-term management of patients with schizophrenia treated with antipsychotics (APs) in real-world practice. This population-based study included adults with schizophrenia and who had received ≥3 deliveries of an AP from 2012–2017, identified using a National Health Data System. Primary endpoints were real-life prescription patterns, patient characteristics, healthcare utilization, comorbidities and mortality. Of the 456,003 patients included, 96% received oral APs, 17.5% first-generation long-acting injectable APs (LAIs), and 16.1% second generation LAIs. Persistence rates at 24 months after treatment initiation were 23.9% (oral APs), 11.5% (first-generation LAIs) and 20.8% (second-generation LAIs). Median persistence of oral APs, first-generation LAIs and second-generation LAIs was 5.0, 3.3, and 6.1 months, respectively. Overall, 62.1% of patients were administered anxiolytics, 45.7% antidepressants and 28.5% anticonvulsants, these treatments being more frequently prescribed in women and patients aged ≥50 years. Dyslipidemia was the most frequent metabolic comorbidity (16.2%) but lipid monitoring was insufficient (median of one occasion). Metabolic comorbidities were more frequent in women. Standardized patient mortality remained consistently high between 2013 and 2015 (3.3–3.7 times higher than the general French population) with a loss of life expectancy of 17 years for men and 8 years for women. Cancer (20.2%) and cardiovascular diseases (17.2%) were the main causes of mortality, and suicide was responsible for 25.4% of deaths among 18–34-year-olds. These results highlight future priorities for care of schizophrenia patients. The global persistence of APs used in this population was low, whereas rates of psychiatric hospitalization remain high. More focus on specific populations is needed, such as patients aged >50 years to prevent metabolic disturbances and 18–34-year-olds to reduce suicide rates.

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Real-world effectiveness of long-acting injectable antipsychotic treatments in a nationwide cohort of 12,373 patients with schizophrenia-spectrum disorders

This mirror-image study aimed to evaluate the real-life effectiveness of long-acting injectable antipsychotics (LAI) in schizophrenia. Patients with schizophrenia initiating LAIs January 2015–December 2016 were enrolled from the French National Health Data System (SNDS). Standardized mean differences (SMD > 0.1 deemed clinically significant) were calculated for psychiatric healthcare resource utilization measures assessed one year before (during oral AP treatment) and one year after LAI initiation. LAI effectiveness was analyzed overall and by age group, gender and compliance to oral AP, defined as exposure to an AP for at least 80% of the year before LAI initiation. 12,373 patients were included. LAIs were more frequently initiated in men (58.1%), young (18–34 years, 42.0%) and non-compliant (63.7%) patients. LAI initiation was effective in reducing the number and duration of psychiatric hospitalizations and psychiatric emergency department (ED) admissions in non-compliant patients (SMD = −0.19, −0.26 and −0.12, respectively), but not in compliant patients. First-generation LAIs, paliperidone and aripiprazole LAIs reduced psychiatric hospitalizations (SMD = −0.20, −0.24, −0.21, respectively) and ED admissions (SMD = −0.15, −0.13, −0.15, respectively). No differences in effectiveness were found for age or gender. In compliant patients, only aripiprazole LAI reduced the number of psychiatric hospitalizations (SMD = -0.13). Risperidone and paliperidone LAIs increased hospitalization duration (SMD = 0.15 and 0.18, respectively). The prescription of LAIs (except risperidone) should be recommended in all non-compliant patients, even in women and patients aged 35 or older. The lower frequency of administration of LAIs than of oral APs may improve compliance and hence reduce the risk of relapse. Aripiprazole LAI may represent a treatment of choice for compliant patients that should be further investigated.

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Analyse coût-efficacité de l’aripiprazole injectable à libération prolongée (AILP) comparé au palmitate de palipéridone (PP) dans le traitement de la schizophrénie en France

ObjectiveThe aim of the study was to estimate the cost-effectiveness ratio of aripiprazole once-monthly compared to once-monthly injectable paliperidone palmitate in the treatment of schizophrenia in France on the basis of results and data from the QUALIFY study. MethodsConsumed resources data measured with a dedicated questionnaire and results on the quality of life scales from the QUALIFY study were combined with French standard unit costs of each collected consumed resources during QUALIFY to estimate the cost-effectiveness ratios of the two products. Multivariate sensitivity analyses were performed to test the combined impact of the different assumptions. ResultsFindings of the study showed greater efficacy on the quality of life (QLS) and psychiatric evaluation scales (CGI-S and CGI-I) observed in QUALIFY of aripiprazole compared with paliperidone palmitate. Findings also suggest a trend (P=0.0733) in the reduction of total costs linked to a statistical decrease (P<0,0001) in drug costs in the aripiprazole group. These findings are reinforced by the probabilistic sensitivity analyses. ConclusionAripiprazole appeared to be more cost-effective than paliperidone palmitate in the French context. Limits of this study are mainly related with the duration of the clinical trial and to assumptions on the transposability of measured consumed resources in the international clinical trial to the French healthcare system.

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Polykystose rénale : analyse des discussions des e-patients sur la blogosphère publique

The goal this study was to understand the preoccupations of e-patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD), through their discussions on social networks, and to compare them with those of members of a specialized association. We collected and analyzed all messages containing an unequivocal expression of the pathology (polycystic kidney disease, PKD, ADPKD, etc.) available on public forums on the French Internet and all french-language messages posted on the forum of the patient group Association Polykystose-France (PKD-France) during 2 years. The automated processing of messages (extraction of themes), using a referential associating each theme with a variety of expressions, allowed classification in different thematic families. 8494themes were extracted from 764 messages sent by 329 different users on 68 public forum websites. The main thematic families were treatments (17%), pathology (16%), signs and symptoms (13%), feelings (11%), healthcare system (7%) and patient life (7%). On the association's forum, 345 messages were sent by 57 different members. The thematic richness was equivalent (number of themes per message: 10.2 versus 11.1 respectively), with 3517 themes, but the thematic families corresponded more to the emotional aspects and daily problems: Feelings (15.5%) came before treatment (14.5%), then anatomy (9%) before the healthcare system (8%) and pathology (7%). Knowing the e-patients’ views expressed on the internet will enable physicians to respond to patients real expectations and correct erroneous perceptions. As for the patients, they will know the leading sites of opinion, shared by their peers.

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Defining the minimal clinically important difference (MCID) of the Heinrichs-carpenter quality of life scale (QLS).

To determine the Minimal Clinically Important Difference (MCID) of the Heinrichs-Carpenter Quality of Life Scale (QLS). Data from the "Schizophrenia Trial of Aripiprazole" (STAR) study were used in this analysis. The MCID value of the QLS total score was estimated using the anchor-based method. These findings were substantiated/validated by comparing the MCID estimate to other measurements collected in the study. Half of the patients (49%) showed improvement in Clinical Global Impressions of Severity (CGI-S) during the trial. The estimated MCID of the QLS total score was 5.30 (standard error: 2.60; 95% confidence interval: [0.16; 10.43]; p < 0.05). Patients were divided into two groups: "QLS improvers" (QLS total score increased ≥ six points) and "non-improvers". The QLS improvers had significantly better effectiveness and reported significantly higher levels of preference for their current medications. There was a statistically significant difference between the two groups in the change in two of the four domains of QLS; "Interpersonal relations" and "Intrapsychic foundations" domains during the study. These findings support the value of the estimated MCID for the QLS and may be a useful tool in evaluating antipsychotic treatment effects and improving long-term patient outcomes in schizophrenia. Copyright © 2015 John Wiley & Sons, Ltd.

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Niveau de vigilance des psychiatres pour les facteurs de risque cardiovasculaire chez les patients schizophrènes

Schizophrenic patients have increased cardiovascular risk factors and morbi-mortality as compared with the general population. To assess the level of French psychiatrists vigilance regarding cardiovascular risk factors in schizophrenic patients. Prospective, transverse, multicentric observational study implemented in France in 2007 and conducted by psychiatrists with a liberal activity. The included patients had to meet the following selection criteria: patients ≥ 18 years old, fulfilling the DSM-IV-TR criteria for schizophrenia, treated or not treated for their schizophrenia, with an ambulatory follow-up, without schizophreniform, schizoaffective, or other psychotic disorder. The psychiatrists "vigilance level" for a given cardiovascular risk factor was defined as a systematic investigation of this cardiovascular risk factor for at least 75% of the schizophrenic patients included in the study by the psychiatrist. A total of 382 psychiatrists included 2242 patients, the data collected for 2222 patients were finally analysed. The mean age was 41 years old, 59% were men. The mean BMI was 27 kg/m(2), 34% of the patients were overweight, 23% were obese. The paranoid and residual schizophrenia were the most frequently described subtypes of the disease (41.3 and 25.0% respectively), 58% of the patients were moderately or markedly ill according to the CGI-S scale. Most of the patients were treated with atypical antipsychotics (77%). Only 58% of the psychiatrists were vigilant for the weight of their patients, 38% for the arterial tension, 25% for the family history of premature coronary disease, 14% for the glycemia, 12% for the triglycerides, 10% for HDL cholesterol, 6% for the waist measurement; 35% of the psychiatrists were vigilant for no cardiovascular risk factor. Less than 30% of the psychiatrists recommended their patients to other specialists to manage cardiovascular disorders. Similarly to other countries, French psychiatrists provide insufficient care of cardiovascular risk factors of schizophrenic patients in their current clinical practice.

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Residual symptoms and functional performance in a large sample of euthymic bipolar patients in France (the OPTHYMUM study)

BackgroundSome residual symptoms were found to be associated with impaired functioning in euthymic bipolar patients, but their impact and relevance are unclear in clinical practice. We re-examined the functional influence of a large set of residual symptoms in 525 euthymic bipolar outpatients using self- and clinician-rated questionnaires (OPTHYMUM study). MethodsThis was a multi-centre, cross-sectional, non-interventional study of adult bipolar outpatients. All patients were euthymic at the time of assessment (YMRS score <8 and BDRS ≤8). Patients with low functioning (GAF score <60) were compared with the rest of the sample. Patients filled in specific questionnaires concerning their perceptions of different residual and subsyndromal symptoms. ResultsNinety-seven (97) psychiatrists included 525 patients. Of them, 35 patients had a GAF score <60. These “low functioning patients” were more frequently unemployed, had presented more manic episodes and psychotic symptoms, used more atypical antipsychotics or benzodiazepines and received less adjunctive psychotherapy. Concerning residual symptoms, they had more frequent emotional subsyndromal symptoms, disruption of circadian rhythms and sexual disorders. They perceived some cognitive deficits and suffered more social and family stigma. LimitationsOur study used an arbitrary GAF cut-off score (60) to separate bipolar patients in two groups (low and satisfactory functioning). ConclusionsResidual symptoms are associated with functional impairment and may represent specific treatment targets. A personalized approach through specific psychotherapeutic programs may lead to more efficient support by the clinician.

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Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial

Clozapine is associated with significant weight gain and metabolic disturbances. This multicentre, randomized study comprised a double-blind, placebo-controlled treatment phase of 16 wk, and an open-label extension phase of 12 wk. Outpatients who met DSM-IV-TR criteria for schizophrenia, who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or =2.5 kg while taking clozapine, were randomized (n=207) to aripiprazole at 5-15 mg/d or placebo, in addition to a stable dose of clozapine. The primary endpoint was mean change from baseline in body weight at week 16 (last observation carried forward). Secondary endpoints included clinical efficacy, body mass index (BMI) and waist circumference. A statistically significant difference in weight loss was reported for aripiprazole vs. placebo (-2.53 kg vs. -0.38 kg, respectively, difference=-2.15 kg, p<0.001). Aripiprazole-treated patients also showed BMI (median reduction 0.8 kg/m(2)) and waist circumference reduction (median reduction 2.0 cm) vs. placebo (no change in either parameter, p<0.001 and p=0.001, respectively). Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein (LDL) cholesterol. There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator's Assessment Questionnaire scores favoured aripiprazole over placebo. Safety and tolerability were generally comparable between groups. Combining aripiprazole and clozapine resulted in significant weight, BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine. Improvements may reduce metabolic risk factors associated with clozapine treatment.

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UK cost-consequence analysis of aripiprazole in schizophrenia: diabetes and coronary heart disease risk projections (STAR study)

Patients with schizophrenia experience elevated rates of morbidity and mortality, largely due to an increased incidence of cardiovascular disease and diabetes. There is increasing concern that some atypical antipsychotic therapies are associated with adverse metabolic symptoms, such as weight gain, dyslipidaemia and glucose dysregulation. These metabolic symptoms may further increase the risk of coronary heart disease (CHD) and diabetes in this population and, subsequently, the cost of treating these patients' physical health. The STAR study showed that the metabolic side effects of aripiprazole treatment are less than that experienced by those receiving standard-of-care (SOC). In a follow-up study the projected risks for diabetes or CHD, calculated using the Stern and Framingham models, were lower in the aripiprazole treatment group. Assuming the risk of diabetes onset/CHD events remained linear over 10 years, these risks were used to estimate the difference in direct and indirect cost consequences of diabetes and CHD in schizophrenia patients treated with aripiprazole or SOC over a 10-year period. Diabetes costs were estimated from the UKPDS and UK T(2)ARDIS studies, respectively, and CHD costs were estimated using prevalence data from the Health Survey of England and the published literature. All costs were inflated to 2007 costs using the NHS pay and prices index. The number of avoided diabetes cases (23.4 cases per 1,000 treated patients) in patients treated with aripiprazole compared with SOC was associated with estimated total (direct and indirect) cost savings of 37,261,293 pounds over 10 years for the UK population. Similarly, the number of avoided CHD events (3.7 events per 1,000 treated patients) was associated with estimated total cost savings of 7,506,770 pounds over 10 years. Compared with SOC, aripiprazole treatment may provide reductions in the health and economic burden to schizophrenia patients and health care services in the UK as a result of its favourable metabolic profile.

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