Characteristics of patients with depression initiating or switching antidepressant treatment: baseline analyses of the PERFORM cohort study.

BACKGROUND: Patients who require a switch in their antidepressant therapy may have different clinical profiles and treatment needs compared with patients initiating or maintaining a first-line antidepressant therapy. METHODS: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (MDD) (PERFORM) study was a 2-year observational cohort study in outpatients with MDD in five European countries. Enrolled patients were either initiating or undergoing the first switch to an antidepressant monotherapy. Baseline data on patients' clinical status, functioning, productivity, quality of life and medical-resource use were compared in a cross-sectional baseline analysis. RESULTS: A total of 1402 patients were enrolled, of whom 1159 (82.7%) provided analysable baseline data. The majority (78.7%) of the analysable population were initiating antidepressant treatment and most (83.6%) were enrolled and followed up by general practitioners. Compared with patients initiating antidepressants, those switching antidepressants (21.3%) tended to have more severe depressive symptoms, greater anxiety, worse health-related quality of life, greater functional impairment, greater medical-resource use and had a different medical history. Limitations included an over-representation of switches due to lack of efficacy among patients who were switching treatment, as patients were selected based on presence of depressive symptoms. CONCLUSIONS: Patients with MDD who are switching treatment for the first time have a different profile and different depression-associated health needs compared with those initiating treatment. Therapeutic management should therefore be adapted for patients who switch. TRIAL REGISTRATION: ClinicalTrials.gov NCT01427439 ; Retrospectively registered 26 August 2011.

Creating an index to measure health state of depressed patients in automated healthcare databases: the methodology.

Background and objective: Automated healthcare databases (AHDB) are an important data source for real life drug and healthcare use. In the filed of depression, lack of detailed clinical data requires the use of binary proxies with important limitations. The study objective was to create a Depressive Health State Index (DHSI) as a continuous health state measure for depressed patients using available data in an AHDB. Methods: The study was based on historical cohort design using the UK Clinical Practice Research Datalink (CPRD). Depressive episodes (depression diagnosis with an antidepressant prescription) were used to create the DHSI through 6 successive steps: (1) Defining study design; (2) Identifying constituent parameters; (3) Assigning relative weights to the parameters; (4) Ranking based on the presence of parameters; (5) Standardizing the rank of the DHSI; (6) Developing a regression model to derive the DHSI in any other sample. Results: The DHSI ranged from 0 (worst) to 100 (best health state) comprising 29 parameters. The proportion of depressive episodes with a remission proxy increased with DHSI quartiles. Conclusion: A continuous outcome for depressed patients treated by antidepressants was created in an AHDB using several different variables and allowed more granularity than currently used proxies.

A Trial-Based Predictive Microsimulation Assessing the Public Health Benefits of Nalmefene and Psychosocial Support for the Reduction of Alcohol Consumption in Alcohol Dependence.

BACKGROUND: Alcohol dependence causes considerable harm to patients. Treatment with nalmefene, aiming to reduce consumption rather than maintain complete abstinence, has been licensed based on trials demonstrating a reduction in total alcohol consumption and heavy drinking days. Relating these trial outcomes to harmful events avoided is important to demonstrate the clinical relevance of nalmefene treatment. METHODS: A predictive microsimulation model was developed to compare nalmefene plus brief psychosocial intervention (BRENDA) versus placebo plus BRENDA for the treatment of patients with alcohol dependence and a high or very high drinking risk level based on three pooled clinical trials. The model simulated patterns and level of alcohol consumption, day-by-day, for 12 months, to estimate the occurrence of alcohol-attributable diseases, injuries and deaths; assessing the clinical relevance of reducing alcohol consumption with treatment. RESULTS: The microsimulation model predicted that, in a cohort of 100,000 patients, 971 (95 % confidence interval [CI] 904-1038) alcohol-attributable diseases and injuries and 133 (95 % CI 117-150) deaths would be avoided with nalmefene versus placebo. This level of benefit has been considered clinically relevant by the European Medicines Agency. CONCLUSIONS: This microsimulation model supports the clinical relevance of the reduction in alcohol consumption, and has estimated the extent of the public health benefit of treatment with nalmefene in patients with alcohol dependence and a high or very high drinking risk level.

A cross-sectional study of functional disabilities and perceived cognitive dysfunction in patients with major depressive disorder in South Korea: The PERFORM-K study.

PERFORM-K was a cross-sectional observational study that investigated functional disability, productivity and quality of life in MDD outpatients in South Korea, and the associations of these with depressive symptoms, perceived cognitive dysfunction and other factors. A total of 312 outpatients who started antidepressant monotherapy underwent a single study interview. Physicians and patients assessed depression severity. Patients also assessed: perceived cognitive dysfunction, functional disability, impaired productivity and quality of life. Patients had moderate to severe depression (MADRS mean total score: 28.9±7.3), and reported marked functional disability (SDS mean total score: 16.7±8.6), impaired productivity (WPAI mean overall work productivity loss: 52.4±31.8%), perceived cognitive dysfunction (PDQ-D mean total score: 29.9±18.6) and impaired quality of life (EQ-5D mean utility index score of 0.726±0.192). Greater functional disability and impairment in daily activities were associated with more severe depression and greater perceived cognitive dysfunction. Irrespective of depression severity, patients with more severe perceived cognitive dysfunction reported worse work-related productivity outcomes (higher presenteeism and greater overall work productivity loss). PERFORM-K confirms the impact of MDD on functional status and well-being in South Korean patients, and highlights the importance of recognising cognitive dysfunction in clinical practice.

The Effects of as-Needed Nalmefene on Patient-Reported Outcomes and Quality of Life in Relation to a Reduction in Alcohol Consumption in Alcohol-Dependent Patients.

BACKGROUND: The objective of this article was to investigate the effect of as-needed nalmefene on health-related quality of life (HRQoL) in patients with alcohol dependence, and to relate changes in drinking behavior and status to HRQoL outcomes. METHODS: This post hoc analysis was conducted on a pooled subgroup of patients with at least a high drinking risk level (men: >60 g/day; women: >40 g/day) who participated in one of two randomized controlled 6-month studies, ESENSE 1 and ESENSE 2. Patients received nalmefene 18 mg or placebo on an as-needed basis, in addition to a motivational and adherence-enhancing intervention (BRENDA). At baseline and after 12 and 24 weeks questionnaires for the Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36), European Quality of life-5 Dimensions (EQ-5D) and the Drinker Inventory of Consequences (DrInC-2R) were completed. RESULTS: The pooled population consisted of 667 patients (nalmefene: 335; placebo: 332), with no notable between-group differences in baseline patient demographics/characteristics. At week 24, nalmefene had a superior effect compared to placebo in improving SF-36 mental component summary scores (mean difference [95% CI], p-value: 3.09 [1.29, 4.89]; p=0.0008), SF-36 physical component summary scores (1.23 [0.15, 2.31]; p=0.026), EQ-5D utility index scores (0.03 [0.00, 0.06]; p=0.045), EQ-5D health state scores (3.46 [0.75, 6.17]; p=0.012), and DrInC-2R scores (-3.22 [-6.12, 0.33]; p=0.029). The improvements in SF-36 mental component summary scores at week 24, and the DrInC-2R total score change from baseline to week 24, were significantly correlated to reductions in heavy drinking days and total alcohol consumption at week 24. CONCLUSIONS: As-needed nalmefene significantly improved almost all patient-reported HRQoL measures included in SF-36 and EQ-5D compared with placebo. These HRQoL gains were significantly correlated to reduced drinking behavior, as determined by reductions in heavy drinking days and total alcohol consumption.

A predictive microsimulation model to estimate the clinical relevance of reducing alcohol consumption in alcohol dependence.

BACKGROUND: Alcohol consumption is one of the most important factors for disease and disability in Europe. In clinical trials, nalmefene has resulted in a significant reduction in the number of heavy-drinking days (HDDs) per month and total alcohol consumption (TAC) among alcohol-dependent patients versus placebo. METHODS: A microsimulation model was developed to estimate alcohol-attributable diseases and injuries in patients with alcohol dependence and to explore the clinical relevance of reducing alcohol consumption. RESULTS: For all diseases and injuries considered, the number of events (inpatient episodes) increased with the number of HDDs and TAC per year. The model predicted that a reduction of 20 HDDs per year would result in 941 fewer alcohol-attributable events per 100,000 patients, while a reduction in intake of 3,000 g/year of pure alcohol (ethanol) would result in 1,325 fewer events per 100,000 patients. CONCLUSION: The potential gains of reducing consumption in alcohol-dependent patients were considerable.

Variability in case mix and peritoneal dialysis selection in fifty-nine French districts.

In France, the use of peritoneal dialysis (PD) as the first-choice treatment varies greatly between districts, as it is already known to do between countries. Baseline clinical factors associated with choice of first modality were analyzed in 10 815 new end-stage renal disease patients in 59 districts. To describe practices at the district level, we used an agglomerative hierarchical classification, with proximity defined by a likelihood-ratio test that compared multivariate logistic regressions of the following factors: age, gender, diabetes, congestive heart failure, severe behavioral disorders, mobility, and employment. To propose a typology, each cluster of districts was described by a multivariate logistic regression. While populations starting PD in France, as elsewhere, are more likely to be young or employed, they are also more likely to be elderly or have congestive heart failure or severe behavioral disorders. Overall, 14% of patients start with PD, but this rate varies significantly across districts, from 0% to 45%. A specific combination of factors was associated with the first-choice modality in each group of districts. This study highlights the lack of consensual medical criteria for this choice and the likelihood that nonmedical factors may explain the observed differences. The high variability suggests that PD can be used in almost all clinical conditions. Accordingly, patient preference should play a more important role in the decision-making process.

Survival benefits of kidney transplantation with expanded criteria deceased donors in patients aged 60 years and over.

BACKGROUND: The proportion of transplant candidates aged 60 years and over listed on the kidney transplant waiting list is increasing, as is the proportion of potential organ donors of this age. We compared in elderly recipients: kidney graft survival of expanded criteria deceased donor (ECD) to nonexpanded criteria deceased donor (NECD), and survival of patients receiving these grafts to those remaining on the waiting list. METHODS: Between 1996 and 2004, a total of 3001 patients aged 60 years and over were registered on the French kidney transplant waiting list, of which 2099 were transplanted. The data were analyzed using Kaplan-Meier methods and Cox models. RESULTS: ECD was defined as presenting at least one of the following factors: age over 60 years than less (relative risk [RR]=1.26; P=0.02), history of arterial hypertension vs. absence (RR=1.34; P=0.01), history of diabetes mellitus vs. absence (RR=1.6; P=0.01), and death due to cerebrovascular accident vs. other cause (RR=1.3; P=0.01). Patients who did not undergo transplantation had an adjusted risk of death 2.54 times higher than that of transplanted patients of the same age (P<0.0001), regardless of the type of graft. The risk was 3.78 times higher than that for patients receiving NECD grafts (P<0.0001) and 2.31 for patients receiving ECD grafts (P<0.0001). CONCLUSION: In elderly patients, transplantation with an ECD kidney was associated with higher survival rates than remaining on the waiting list. This result suggests that the identification and use of ECD kidney grafts should be optimized, given changes in the characteristics of potential donors and recipients.

Access to, and outcome of, renal transplantation according to treatment modality of end-stage renal disease in France.

BACKGROUND: Although peritoneal dialysis (PD) is recognized as one of the methods of treatment of end-stage renal disease (ESRD), there have been recurrent concerns about the access of patients treated by this modality to kidney transplantation (KTx), as well as reports showing increased complications of KTx in such patients, such as graft thrombosis and infections. METHODS: The aim of this study was to provide a comprehensive view of the impact on transplantation of pretransplant modality of treatment of ESRD using a multivariate analysis of the French database. From 1997 to 2000, after exclusion of pediatric patients, multiple transplantations, and living donors, 6420 were patients registered on the waiting list, and 3464 were transplanted. RESULTS: Using a Cox proportional hazard analysis, we found a shorter waiting time for PD patients (RR 0.71, P < 0.0001), which became equivalent to hemodialysis (HD) patients when taking into account the transplant center as a variable (RR 1.0, P= 0.95). Concerning graft survival, only preemptive transplantation had a significant impact, being associated to a decreased risk of graft failure (RR 0.46, P= 0.005). Conclusion. Our study supports the concept that the choice of any pretransplant dialysis modality does not influence waiting time for transplant or the results of transplantation.

[Regional differences in the access to liver transplantation in France]. / Variations géographiques de l'accès à la greffe de foie en France.

AIM: This study evaluated regional differences in registration on the waiting list and access to liver transplantation in France. METHODS: The annual incidence of registration on the waiting list was calculated with the number of transplantation candidates registered in each region between 1996 and 1998 and was used as an indicator for access to the waiting list. The median waiting time before receiving a graft was estimated for patients registered between 1992 and 1998 by the Kaplan Meier method using transplantation as the event. This was used as an indicator for access to transplantation. Shortage of liver grafts was based on the ratio between the number of registered patients and the number of transplantations. RESULTS: The national incidence rate on the liver transplantation waiting list was 11.5 candidates per million inhabitants (pmi). There were no significant statistical differences among regions but it was high for the Rhône-Alpes region (18.6 pmi) and low for the French West Indies (3.6 pmi). The median waiting time before a graft is 2.2 months, and varied from 0.5 month to 3.8 months in French regions (p<0.001). Lack of a graft was strongly correlated with the median waiting time but not with the harvested liver rate. CONCLUSION: Although there is no statistical significant difference in access to the waiting list for liver transplantations, access to grafts differs among the regions in France.