Antidepressant switching patterns in the treatment of major depressive disorder: a General Practice Research Database (GPRD) Study.

AIMS: To investigate switching patterns of major antidepressant treatments and associated factors in a primary care adult population with major depressive disorder (MDD) using data from the General Practitioner Research Database (GPRD). METHODS: A retrospective cohort study was conducted using the GPRD. The study included patients with MDD, aged [18-70], with a new prescription for amitriptyline, citalopram, escitalopram, fluoxetine, paroxetine, sertraline or venlafaxine between January 1, 2001 and September 30, 2003 and having no antidepressant prescription in the 6 months preceding index date. Switching of antidepressant treatment was defined as a prescription of a different antidepressant among all available marketed antidepressant treatment at this time (no restriction of compound) from 1 month before up to 2 months after the calculated end of the previous antidepressant treatment. Survival analysis techniques were used to describe switching of antidepressant and time to switch. Profiles of switchers were described and by-treatment analyses performed. RESULTS: Data from over 59,000 patients showed that 16% switched antidepressants. Seventy-two per cent of switches appeared within 3 months after treatment initiation. Within switchers, median time to switch was 53 days. Switching patients had generally a more severe psychiatric profile, including more previous episodes of depression or other psychiatric disorders. They also had a higher proportion of concurrent psychiatric disorders (especially anxiety) and concomitant prescription of anxiolytics or hypnotics. Patients initially prescribed amitriptyline were almost twice as likely to switch (27%) as patients prescribed venlafaxine (17%) or an SSRI (15%). CONCLUSIONS: This population-based study confirmed that antidepressant switch is more likely to occur within the first 3 months of treatment and in patients with a more severe psychiatric profile. A particular attention paid to these patients within the early phase of treatment may therefore help to improve their management.

The use of contrast media in deceased kidney donors does not affect initial graft function or graft survival.

Patients receiving cadaveric kidney transplants often experience delayed graft function. As iodinated contrast media injection (ICMI), necessary for cerebral angiography, which is often used to diagnose brain death, can be nephrotoxic, we compared renal function recovery (RFR) and 1-year and long-term graft survival according to the method used to diagnose brain death. Data from 9921 cadaveric kidneys, transplanted between 1 January 1998 and 31 December 2003, were retrieved from the French National Registry for organ donation. We defined RFR as the number of days for the recipient to reach a plasma creatinine less than 250 mumol/l, and/or a 24-h urine output greater than 1000 ml. RFR and 1-year and long-term graft survival were compared between four different donor groups (according to ICMI and diabetes mellitus). A total of 41.5% of deceased donors received ICMI before organ procurement and 1.95% of them were diabetic. History of ICMI or diabetes in the donor did not influence RFR or 1-year graft survival. Long-term graft survival was decreased in the group of patients transplanted with a diabetic graft as compared to patients transplanted with a non-diabetic graft (P=0.001). History of ICMI in the donor did not affect long-term graft survival in the non-diabetic donor group (P=0.2); however, in the diabetic group, ICMI tended to decrease long-term graft survival (P=0.056). ICMI did not affect RFR or graft survival in non-diabetic deceased donors. However, its use in diabetic deceased donors requires further study.

Monitoring organ donor rates: a predictive model based on routinely available data in France applied to the year 2002.

Temporal trends in organ donor harvesting rates are subject to variability. It is important to detect variations as early as possible using current data. We developed a predictive model for monitoring harvesting activity using the number of donors harvested monthly between 1996 and 2001. A Poisson model was used to predict the number of donors harvested each month along with their confidence intervals. This model also updates, on a monthly basis, the predicted number of donors for the current year. During 2002, the number of donors observed each month followed the predicted monthly variations, but a significant increase was observed in March and May. These models can be used by transplantation agencies for monitoring purposes and for the evaluation of organ donation programmes.

[Inequalities to the access of renal transplantation for French patients living in the overseas French territories]. / Disparités d'accès à la greffe rénale pour les malades résidant dans les Départements et Territoires d'Outre-Mer.

This study explored the access to the French national renal transplantation waiting list and the waiting time before transplantation for the patients with ESRD on dialysis living in the FOT. Overseas health authorities gave data on ESRD incidence and prevalence. Data on patients registered between 1997 and 2000 were extracted from the French national waiting list (390 patients from the FOT and 9378 from continental France). Registered prevalence of ESRD in FOT (726 to 1418 per million population (pmp)) were higher than continental France (580 pmp). The yearly incidence of registration on the national French waiting list was 36 pmp. The same figure was observed in the FAT (French Guyana and Caribbean's islands: 36.8 to 43 pmp), very low in New Caledonia and Tahiti (7.7 and 18.1 pmp), and very high in the Reunion Island, where a renal transplantation unit is available (77.5 pmp). Median waiting times before transplantation varied significantly, FAT: 35.4 months, Reunion Island: 9.9 months, Pacific Territories: 8.8 months and the Metropolitan territory: 12.2 months. After adjustment on risk factors known to be associated with the waiting times before transplantation, we still observed a longer waiting time for patients from FAT (RR = 1,4, p < 0.05) and a lower waiting time for patients from Reunion Island (RR = 0.6, p < 0.001) compared to waiting time observed in patients from continental France. Consequently, transplantation teams in FAT must be developed.

[Geographic variations in access to heart transplantation in France]. / Variations géographiques de l'accès à la greffe cardiaque en France.

This study was undertaken to determine whether there were regional variations in the access to the national waiting list for cardiac transplantation and in access to cardiac transplantation itself in France. The incidence of inscription on the waiting list for transplantation was calculated for new candidates living in each region between 1998 and 2000, indicating the level of access to the waiting list. The average interval before transplantation between 1995 and 2000 was calculated by the Kaplan-Meier method. The regional lack of transplant organs was estimated by the ratio of the difference between patients inscribed on the waiting list and those operated, over the number of patients operated. The overall national incidence of inscription of the waiting list for cardiac transplantation was 8 new patients per year per million inhabitants with a range of 1.7 in Corsica to 12.1 in Lorraine. The regional incidence was lower than the national reference in 5 regions in higher in 4 regions. There was a strong attraction of patients to the Ile-de-France, Pays de la Loire and Rhone-Alpes regions. The average waiting time for transplantation in France was 3.7 months and ranged from 1.2 months in Brittany to 15.4 months in Aquitaine (p < 0.001). The degree of regional lack of transplant organs was significantly and positively correlated with the average waiting time for transplantation. The results of this study show that there are regional differences in the incidence of inscription on the waiting list for cardiac transplantation in France and a significant variation in waiting times for cardiac transplantation, and therefore, in access to cardiac transplantation.

Organ allocation in pediatric transplantation in France.

In France, ministerial decrees in 1995 and 1996 gave children under 16 who are awaiting transplantation national priority for kidneys and livers from donors under 16, and regional priority for kidneys and livers from donors under 30. We analyzed the effects of these changes on waiting time, death on the waiting list, and balance between demand and supply. The percentage of children who received a transplant during the year of registration increased from 40% in 1993 to 67% in 1998 for kidney transplantation, but only from 50% to 67% for liver transplantation. The number of new children registered on the renal transplant waiting list (84 in 1998) and the number transplanted (85 in 1998) are balanced. But, because of the number of children still on the waiting list at the end of each year, there remains an imbalance of about 70 for kidney transplantation. For liver transplantation, there remains an imbalance of about 35. Death on the renal transplant waiting list has been below 2% since 1993. Death on the liver transplant waiting list decreased from 10-20% in 1993-1995 to 3% in 1998. The number of children who died on the thoracic organ waiting list in 1998 was the same as the number transplanted. In conclusion, the new rules governing organ allocation to children in France have shortened waiting time for renal transplantation, but not for liver transplantation. Many children still die on the waiting list for thoracic organ transplantation.

Analysis of the French liver transplant waiting list, 1992-1996.

BACKGROUND: In organ transplantation, each country has specific rules of allocation. We have retrospectively evaluated the French liver transplant waiting list for the period 1992-1996, during which time the rules for allocation remained stable. Mortality while on the waiting list and waiting times were the two principal endpoints. METHODS: Using the Etablissement Français des Greffes (EFG) registry, the study was conducted in three steps: (1) description of the waiting list population; (2) analysis of the outcome of patients, with the use of a logistic model to explain death while on the waiting list; (3) estimation of waiting times and use of a Cox model to explain waiting times. RESULTS: The distribution of patients with regard to degree of urgency, age, blood type, and liver disease was variable according to the the EFG region. The outcome of patients was variable according to blood type and to EFG region. Patients classed as "extremely urgent" did not have a different outcome compared to elective patients. The logistic model indicated that two factors influenced the death: blood group and EFG region. Waiting times were variable according to EFG region; age and blood group had an influence on waiting times for a graft. The Cox model indicated the independent influence of EFG region on waiting times. CONCLUSION: We found geographical disparities between patients with respect to time on the waiting list. However, the database must be improved by including the risk profile of each patient, leading to changes in rules for a better allocation of transplants.

[Evaluation of the results of organ transplantation in France: is there a center effect?]. / Evaluation des résultats des greffes d'organes en France: existe-t-il un effet centre?

The evaluation of the results of organ allografts for each type of organ and for each center is one of the prioritary missions of the Etablissement français des Greffes (EfG). The objectives, the methodology and the results of this evaluation have been defined and discussed with all the organ transplantation teams, after a preliminary work of the Conseil Médical et Scientifique of the Etablissement. This paper describes the evaluation experiment conducted by the EfG between 1995 and 1998. The main objectives of this first phase of the evaluation project are the identification of centers with outside of the norm results and the study of the relationship between the number of transplants performed by each center and the quality of their results. The chosen quality indicators are the excess in the patients mortality rate, computed one year after the first transplantation, for vital organs, and in the one year kidney graft loss rate for kidney transplantation. The excess of mortality is defined as the difference between observed and expected mortality rates. The expected mortality rate is estimated, for each program, by a statistical model based on a set of patient specific risk factors. All the vital organ transplantation teams who have performed more than 10 transplants between 1991 and 1995, and all the kidney transplantation teams who have performed more than 15 transplants between 1991 and 1996 have been included in the study. The main results of this evaluation experiment are the following ones: even if the intercenter variability of the results was statistically significant, it remained of low magnitude, particularly for heart, liver and kidney transplantation. None of the evaluated centers presented results outside of the norm. The results were positively correlated to the number of transplants for liver and lung transplantation. This was not the case for heart and kidney transplantation; this relationship is difficult to analyze for heart-lung transplantation, due to the small number of centers included. Thanks to the data base constituted since 1959 by all the organ transplantation teams, and in spite of the partially retrospective nature of this study, which explains its limits, this evaluation experiment, opens a perspective of extension to other domains of public health. In the future, however, this kind of evaluation should be prospective; a project aimed to developing the evaluation of the results of organ transplant actions in real time was defined and is currently on-going.