[Appropriate medication prescribing in older people]. / Bon usage des médicaments chez le sujet âgé.

Drug-induced adverse effects are one of the main avoidable causes of hospitalization in older people. Numerous lists of potentially inappropriate medications for older people have been published, as national and international guidelines for appropriate prescribing in numerous diseases and for different age categories. The present review describes the general rules for an appropriate prescribing in older people and summarizes, for the main conditions encountered in older people, medications that are too often under-prescribed, the precautions of use of the main drugs that induce adverse effects, and drugs for which the benefit to risk ratio is unfavourable in older people. All these data are assembled in educational tables designed to be printed in a practical pocket format and used in daily practice by prescribers, whether physicians, surgeons or pharmacists.

Systematic review with meta-analysis: infliximab and immunosuppressant therapy vs. infliximab alone for active ulcerative colitis.

BACKGROUND: The benefit of the combination of infliximab (IFX) and immunosuppressant (IS) therapy is debated in ulcerative colitis (UC). AIMS: To determine whether the combination of IFX and IS therapy is more effective than infliximab alone for active UC regardless of prior IS use. METHODS: We identified all controlled trials including patients with moderate-to-severe active UC, treated by either IFX or combined IFX-IS therapy. The main outcome was clinical remission at 4-6 months. Two statistical methods were used, Mantel-Haenszel and Der-Simonian and Laird. Inter-trial heterogeneity was taken into account and publication bias was assessed. RESULTS: Four controlled trials were analysed and included in the meta-analysis. These four trials included 765 patients, 389 treated with IFX alone and 376 treated with IFX and IS. At 4-6 months' therapy, the clinical remission rate was significantly lower for the IFX monotherapy group OR 0.50, 95% CI [0.34-0.73], P < 0.01 (P-heterogeneity = 0.49). The Harbord test did not show evidence of publication bias (P = 0.29). Calculation of an adjusted OR using the Duval and Tweedie method did not significantly modify results [OR 0.63, 95% CI (0.47-0.85)]. According to Orwin's formula, four additional medium-sized nonsignificant studies would be necessary to reduce the effect size to a nonsignificant value. At 12 months of therapy, there was no significant difference between the two groups: OR 0.60, 95% CI [0.17-2.06], P = 0.41 (P-heterogeneity = 0.01). CONCLUSION: Combination therapy with IFX-IS is more effective than IFX alone for achieving and maintaining clinical remission at 4-6 months for patients with moderate-to-severe ulcerative colitis, regardless of prior IS use.

Tacrolimus and the risk of solid cancers after liver transplant: a dose effect relationship.

Although increased rates of solid organ cancers have been reported following liver transplantation (LT), the impact of quantitative exposure to calcineurin inhibitors (CNI) remains unclear. We have therefore probed the relationship between the development of solid organ cancers following LT and the level of CNI exposure. This prospective single-center study was conducted between 1995 and 2008 and is based on 247 tacrolimus-treated liver transplant recipients who survived at least 1 year following surgery. The incidence of cancer was recorded, and the mean blood concentration of tacrolimus (TC) was determined at 1 and 3 years following LT. The study results indicate that 43 (17.4%) patients developed de novo solid cancers. Mean TC during the first year after LT was significantly higher in patients who developed solid organ tumors (10.3 ± 2.1 vs. 7.9 ± 1.9 ng/mL, p < 0.0001). Independent risks factors in multivariate analysis were tobacco consumption before LT (OR = 5.42; 95% CI [1.93-15.2], p = 0.0014) and mean annual TC during the first year after LT (p < 0.0001; OR = 2.01; 95% CI [1.57-2.59], p < 0.0001). Similar effects were observed in 216 patients who received tacrolimus continuously for ≥3 years. It appears therefore that CNI should be used with caution after LT, and that new immunosuppressive therapies could deliver significant clinical benefits in this regard.

[Did the recommendation of the French public health council modify the antipapillomavirus vaccines' prescription level?]. / Impact de la modification d'avis du Haut Conseil de la santé publique (HCSP) sur le taux de prescription des vaccins papillomavirus humains en région Midi-Pyrénées.

BACKGROUND: In France, two vaccines are approved for prevention of papillomavirus infection: Cervarix(®) and Gardasil(®). The 17th of December 2010 the French High Committee of Public Hearth changed its recommendation about Cervarix(®) and decided that no scientific element justified a preference using Gardasil(®). This notification was published the 25th of January 2011. Our study aimed to determine whether this decision changed medical prescriptions. METHODS: An ecological study was performed with reimbursement data for the two vaccines. We performed a Chi(2) test for qualitative variables and Student's t test for quantitative variables. RESULTS: A significant difference was observed between the prescription of Cervarix(®) before and after the 25th January 2011. The difference favored increased prescription, compared to Gardasil(®) (P ≤ 0.05). CONCLUSION: This variation can be explained by the impact of recommendations for medical decisions. The strong involvement of pharmaceutical firms in medical education may explain why prescribers reacted so rapidly after the publication of the new recommendations.

[Causes of early mortality after liver transplantation: a twenty-years single centre experience]. / Mortalité trois mois après transplantation hépatique : étude monocentrique sur une période de vingt ans.

OBJECTIVE: To define the causes of mortality of patients who died within the first three months after a liver transplantation. TYPE OF STUDY: Retrospective, observational, and single centre study. PATIENTS AND METHODS: Between March 1989 and July 2010, all patients who died within three months after a liver transplantation were included. Demographic characteristics, preoperative and peroperative data, donor characteristics, postoperative complications and causes of mortality were collected. RESULTS: Among the 788 performed liver transplantations, 76 patients died in intensive care unit (11%). The main indications of liver transplantation were alcoholic cirrhosis (30%), hepatitis C (28%), hepatocarcinoma (15%), primitive or secondary biliary cirrhosis (10%). Fifty percent of the patients were categorized as Child C. The main causes of death were non-function or dysfunction with retransplantation contra-indication graft (18%), sepsis (18%), neurological complications (12%), hemorrhagic shock (13%), (9%), multiorgan failures (5%), cardiac complications (6%). CONCLUSION: In this study, the main causes of mortality were infectious, neurological and hemorrhagic. These results emphasize the necessity for better control of sepsis, haemorrhage and immunosupressors.

[Liver transplantation in a patient with alcoholic cirrhosis: discussion about nonabstinence]. / Discussion d'une transplantation hépatique chez un patient cirrhotique alcoolique incomplètement sevré.

Liver transplantation is the recognized treatment for serious cases of alcoholic cirrhosis. However, due to their poor image within society, patients with alcoholic cirrhosis are often less referred to transplant centres. This is even more surprising since in terms of patient' and graft's survival, the results of transplantation are comparable, if not better, than in other indications. Transplantation is the treatment for the liver disease, not a treatment for alcoholism. In the case of severe alcoholic disease, a relapse is neither surprising nor unacceptable or insignificant if severe. In this case, it has an impact on the long-term survival, notably due to mortality by cancer. All the medical teams carrying out transplants agree that abstinence is necessary when a patient is being evaluated for liver transplantation. However, it is not proven that a set period of 6 months' abstinence prior to the transplantation can modify the results. The problem of alcoholism must be treated specifically in terms of addiction both before and after transplantation.

[Codification procedures for medical acts and diagnostic procedures in dermatology and allergology]. / Comment coder les actes et les diagnostics en dermato-allergologie ?

For a number of years, the French health system has utilized an activity-based fee scale (T2A) with remuneration of technical acts based on a coding system (CCAM). In this article, we present the nomenclature of the various clinical and biological acts undertaken in dermatology and allergology.

Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis.

BACKGROUND: Proteasomes are the main non-lysosomal proteolytic structures which regulate crucial cellular processes. Circulating proteasome levels can be measured using an ELISA test and can be considered as a tumour marker in several types of malignancy. Given that there is no sensitive marker of hepatocellular carcinoma (HCC) in patients with cirrhosis, we measured plasma proteasome levels in 83 patients with cirrhosis (33 without HCC, 50 with HCC) and 40 controls. METHODS AND RESULTS: Patients with HCC were sub-classified into three groups according to tumour mass. alpha-Fetoprotein (AFP) was also measured. Plasma proteasome levels were significantly higher in patients with HCC compared to controls (4841 (SEM 613) ng/ml vs 2534 (SEM 187) ng/ml; p<0.001) and compared to patients with cirrhosis without HCC (2077 (SEM 112) ng/ml; p<0.001). This difference remained significant when the subgroup of patients with low tumour mass (proteasome level 3970 (SEM 310) ng/ml, p<0.001) was compared to controls and patients with cirrhosis without HCC. Plasma proteasome levels were independent of the cause of cirrhosis and were weakly correlated with AFP levels. With a cut-off of 2900 ng/ml, diagnostic specificity for HCC was 97% with a sensitivity of 72%, better than results obtained with AFP. Diagnostic relevance of plasma proteasome measurement was also effective in low tumour mass patients (sensitivity 76.2% vs 57.1% for AFP). CONCLUSION: The plasma proteasome level is a reliable marker of malignant transformation in patients with cirrhosis, even when there is a low tumour mass.

Nocardiosis revealed by thyroid abscess in a liver--kidney transplant recipient.

Nocardiosis is a life-threatening infection, particularly among immunocompromised patients, which usually affects lungs, skin and central nervous system. We report a case of disseminated nocardiosis revealed by suppurative thyroiditis in a liver-kidney transplant recipient with poor nutritional status at the time of infection. Nocardia Asteroides was isolated from fine-needle aspiration material of the thyroid abscess. Clinical manifestations resolved after surgical drainage of the thyroid abscess, prolonged antibiotherapy and diminution of immunosuppressive regimen. Clinicians should be aware of this entity, as Nocardia Asteroides may need more than 5 days of culture to be isolated.

Transferrin receptor-2 gene and non-C282Y homozygous patients with hemochromatosis.

More than 80% of the patients affected by hereditary hemochromatosis, a common inherited iron disorder, are homozygotes for the 845G --> A (C282Y) mutation of the HFE gene. However, depending on the population, 10-20% of hereditary hemochromatosis can be linked either to other HFE genotypes, particularly the compound heterozygous state for C282Y and the 187 C --> G (H63D) mutation, or to mutations of new other genes. Recently, Camaschella et al. (Nat. Genet. 25, 14-15, 2000) identified a stop mutation (exon 6 nt 750 C --> T, Y250X) on the transferrin receptor-2 (TFR2) gene in two unrelated Sicilian families with hereditary hemochromatosis. The TFR2 gene is a transferrin receptor gene homologue that seems to be involved in iron metabolism. Moreover, one of the patients described by Camaschella et al. was a H63D homozygote. H63D homozygosity can be associated with various phenotypes from asymptomatic subjects to patients with a typical form of hereditary hemochromatosis. Thus, the Y250X mutation could be the molecular defect responsible for hereditary hemochromatosis in subjects with atypical HFE genotypes. We have searched for the Y250X mutation in 63 unrelated French subjects. Forty-three had a diagnosis of hereditary hemochromatosis based on classical criteria. This group included 12 H63D homozygotes, 3 C282Y heterozygotes, and 3 patients with none of the two most prevalent HFE mutants. These 18 patients had no other HFE sequence change and were subsequently subjected to DNA sequencing of the 15 last exons and flanking sequences of the TFR2 gene. The 25 remaining hereditary hemochromatosis patients who were tested for the Y250X mutant were compound heterozygotes for the C282Y and H63D mutations. Finally, we also tested for this TFR2 mutation 20 H63D homozygotes with milder manifestations of iron overload and no acquired cause of iron overload. None of the 63 tested subjects had the Y250X mutation. Concurrently, none of the 18 hereditary hemochromatosis patients who had their TFR2 gene sequenced had any deleterious mutation. Thus, TFR2 mutations are not responsible for hemochromatosis in non-C282Y homozygous patients of our area.

Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?

BACKGROUND: First considered as a polymorphism of the HFE gene, the H63D mutation is now widely recognised as a haemochromatosis associated allele. But few H63D homozygotes with clinical manifestations of hereditary haemochromatosis (HH) have been reported. Concurrently, an increasing number of genes have been shown to interact with HFE in iron metabolism. AIMS: To describe the clinical expression of iron overload (IO) associated with H63D homozygosity, and search for potential genetic modifiers (within the HFE or other genes) that could explain the variability of the phenotypes. PATIENTS AND METHODS: We retrospectively analysed the clinical phenotype of 56 H63D homozygotes referred for a personal or family history of IO. For each subject we examined intragenic HFE haplotypes and transferrin receptor (TfR) gene polymorphisms and searched for the Y250X mutation on the TFR2 gene. Additionally, we sequenced the HFE gene of H63D homozygotes with HH. RESULTS: Fifty of 56 subjects had biological and/or clinical abnormalities of iron metabolism. Up to two thirds of patients (n=34) had no acquired cause of IO. Among these, 12 had a phenotypic diagnosis of HH. In the iron loaded group there was a strong prevalence of male patients. No correlation was found between the potential genetic modifiers and phenotypes. No additional mutation of HFE was identified. CONCLUSION: The variable phenotypes associated with H63D homozygosity do not appear to be linked to other HFE mutations, to the TFR2 Y250X mutation, or to HFE or TfR gene intragenic polymorphisms. The exact role of H63D homozygosity in IO and HH needs to be further investigated in unselected populations.

[Medico-economic impact of the Program of Medicalization of the Information System on hospital stay for myocardial infarction: influence of the quality of data collection and hospitalization length]. / Impact médico-économique du PMSI sur les séjours pour infarctus du myocarde: influence de la qualité du recueil et de la durée d'hospitalisation.

The aim of the Medicalisation Program of the Information System was to describe the activity of hospital for budget allocation. This work concerned the whole hospitalizations in the unit of intensive care of cardiology of Dijon for a myocardial infarction (MI) during the 1st half of 1998 (59 patients). The objectives of this study were: 1) the estimate of the real cost of MI management; 2) the comparison of this cost with the reference cost, determined from the data of the National Basis of Costs (BNC); 3) the economic impact of the quality of coding. The real global cost of MI was estimated at 2,323,542 FF (average by patient: 39,382 +/- 15,718 FF). Sixty eight per cent of the costs are directly related to the standing fixed overheads; in contrast, the medical and the therapeutic acts accounted for only 32% of the estimated real cost. A 52% over-estimation was highlighted between the estimated real cost and the cost of reference (p < 0.001). The errors of coding accounted for an under-estimation of only 3.6% of the cost of reference. The duration of hospitalization was significantly higher than the stay length taken from the national reference database (12.9 +/- 5.4 versus 9.2 +/- 2.1 days; p < 0.001), and was mainly responsible for these discrepancies of costs.

[Melanoma in organ transplant patients]. / Mélanome chez le transplanté.

OBJECTIVE: The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. PATIENTS AND METHODS: This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. RESULTS: Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean 15 months. The other 12 patients are still alive with a mean 3 year course since tumor treatment. We tried to determine the relative risk of developing melanoma in the renal transplant population (14 cases). The number of expected cases of melanoma was 5.54, giving a relative risk of 2.5. DISCUSSION: Only 4 studies have shown an increase in the incidence of melanoma in the renal transplant population: approximately 2 to 5-fold. In our study, the 2.5-fold increase in melanoma was estimated with an average 5 year follow-up and an average 5 year immunosuppressive therapy. This is probably an underestimation of risk because we were unable to make an exhaustive collection of cases of melanomas even though transplant recipients undergo more physical examinations than a reference population. The mean latency period from transplantation to melanoma diagnosis was 63 months, as in other studies. Histological examination showed that a precursor nevus is frequent with weak host cellular response to the tumor. The prognosis of these melanomas remains difficult to predict, but in our study, it would not appear to be as poor as expected. Discontinuation of immunosuppressive therapy would not appear to be necessary except in the presence of metastasis. Finally, our study demonstrates the importance of good patient follow-up, even after graft rejection due to the persistent risk of melanoma.

[Human immunodeficiency virus infection in patients over 60 years of age. A cohort study of 31 patients followed-up at the Regional University Hospital Center of Bordeaux]. / Infection par le virus de l'immunodéficience humaine chez les personnes âgées de plus de 60 ans. Une étude de cohorte de 31 patients suivis au CHRU de Bordeaux. Le Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.

Thirty-one patients aged 60 years or more and infected with the human immunodeficiency virus type 1 (HIV-1) were followed up retrospectively and prospectively at the Regional University Hospital of Bordeaux. These patients represented 2.3 percent of all HIV infected patients followed up by the AIDS Clinical Epidemiology Group of Aquitaine. The male-to-female sex ratio was 1.4/1. Contamination resulted from blood transfusion in 58 percent of the cases. In 45.2 percent of these patients the belated diagnosis was revealed by a pathology pointing to AIDS. The most frequent clinical signs were candidiasis, herpes zoster or neurological manifestations which created a difficult differential diagnosis problem with senile dementia. The prognosis of the HIV infection was severe, with a 39.7 percent probability of survival at 18 months (confidence limits 95 percent: 18.6%, 60.8%). This prognosis could be improved by an earlier diagnosis and by a treatment suitable for elderly people.

[Remission of rheumatoid arthritis. Apropos of 32 case reports]. / La rémission de la polyarthrite rhumatoïde. A propos de 32 observations.

The remission of rheumatoid arthritis is a generally accepted concept, although few studies have been performed in this area. The authors report 32 cases of rheumatoid arthritis in remission in a population of 300 patients (10.7%). These cases of rheumatoid arthritis did not present any distinctive signs in comparison with the other patients. The remission was obtained an average of 6.5 years after the onset of the disease and has lasted, to date, for an average of 2.55 years. 30 of the 32 patients were still in remission at the last consultation. The criteria of remission proposed by the ARA are confirmed by these cases. The authors raise the question of the influence of basic treatment on the incidence of remission.