Diagnosis, quality of life, and treatment of patients with Hunter syndrome in the French healthcare system: a retrospective observational study.

BACKGROUND: Mucopolysaccharidosis II (MPS II) is associated with a broad spectrum of chronic and progressive, life-limiting symptoms. Idursulfase is approved for MPS II enzyme replacement therapy (ERT) in over 50 countries. This retrospective study evaluated the MPS II burden, organization of clinical care, and effects of idursulfase treatment on the disease in France. METHODS: MPS II patients who had received idursulfase ERT in the French healthcare system were enrolled. In addition to clinician and patient questionnaires, the Clinical Global Impression-Improvement (CGI-I); Patient Global Impression-Improvement (PGI-I); KIDSCREEN-27, and EuroQoL-5D for adult patients scales were used to assess quality of life (QoL) and efficacy. RESULTS: Fifty-two patients were enrolled from 5 sites in France. The majority of patients (69.2%) presented a severe MPS II phenotype with progressive neurocognitive impairment. Major impacts on QoL were apparent, with at least 1 member of the family having to reorganize working hours (45.5%) or to stop working (22.7%). KIDSCREEN-27 and EuroQoL-5D scale scores were well below those for referent (control) populations. Most families (70.0%) experienced a diagnostic delay of at least 3 years after the initial observation of symptoms. The MPS II diagnosis was often delivered without adequate sensitivity, psychological support, or comprehensive information about the disease. The study population had received a mean of 3.8 ± 1.3 years ERT. Forty-four percent of patients with the attenuated phenotype (without progressive neurocognitive impairment) showed symptom improvement during both the first year (Period 1) and from the end of the first year of treatment to "the present" (Period 2), as measured by CGI-I/PGI-I. 30.3% and 9.1% of severe patients experienced symptom improvement during Periods 1 and 2, respectively, while 63.6% and 51.5% displayed no change. The most common adverse reactions reported were skin rash and other infusion-associated reactions. CONCLUSIONS: MPS II adversely affects multiple domains of QoL for patients and families, requiring multiple healthcare services and social aid programs. The majority of patients with either phenotype experienced either improvement or stability in their symptoms during the first year of ERT, but this was clearly less so for patients with the severe phenotype after the first year of treatment.

Hereditary angioedema with C1 inhibitor deficiency: clinical presentation and quality of life of 193 French patients.

BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially life-threatening disease. New specific treatments are available. OBJECTIVE: To identify patients' features and patients' best therapeutic option. METHODS: A 1-year, multicenter, retrospective study was performed. The primary objective was to examine the clinical presentation of HAE. Secondary objectives included patient characteristics, management of HAE over 12 months, and health-related quality of life using the SF-36v2 questionnaire. RESULTS: One hundred ninety-three patients were included, and 69.4% were women. In the 12-month period, the mean number of HAE attacks was 7.6. Among the 568 reported attacks, localizations were the abdomen (57.1%), peripheral limbs (42.5%), upper airway (7.9%), and face (6.9%); 31.6% of attacks were severe and occurred statistically more often in women (P < .02). Compared with a population of allergic patients, all age- and sex-adjusted scores were significantly lower in patients with HAE (P < .05) except for the physical component summary. Health-related quality of life negatively correlated with the annual number of attacks and was markedly altered for patients having more than 5 attacks per year (P < .05 for all dimensions). CONCLUSION: HAE is a severe disease that places a heavy burden on quality of life.

[Screening of clinical benign prostatic hypertrophy in general practice: survey of 18,540 men]. / Dépistage de l'hypertrophie bénigne de la prostate clinique en médecine générale: enquête sur 18.540 hommes.

OBJECTIVES: Urinary symptoms, mainly attributed to benign prostatic hyperplasia (BPH), are frequent in men over the age of 50, but their prevalence appears to be largely underestimated, as patients fail to report this complaint. We therefore tried to identify the reasons for failure to seek medical attention by symptomatic but undiagnosed patients and to evaluate the management of these patients by general practitioners. PATIENTS AND METHODS: This cross-sectional, prospective, multicentre epidemiological survey studied patients over the age of 50 without a diagnosis of BPH and not spontaneously reporting any urological symptoms. A clinical interview was systematically performed in order to identify such symptoms and the reasons why the patient did not complain of these symptoms. The management by general practitioners was then analysed, including appropriate clinical and complementary examinations to attribute the symptoms to BPH. RESULTS: 18,540 outpatients were recruited by 2,200 general practitioners. The prevalence of "confirmed BPH" (diagnosis established at the visit and I-PSS > or = 8, Bother score (I-PSS-Q) > or = 3) was 49.4%. These patients (mean age: 66 years) had suffered from urinary symptoms for almost 3 years; 70.1% of them reported to be at least "mostly dissatisfied" if they were to spend the rest of their life with these urinary symptoms. The mean I-PSS was 14.1 and 86.7% of patients were considered to be moderately symptomatic. The I-PSS increased with age (p = 0.001) and the history of symptoms (p = 0.001). The I-PSS-Q increased in parallel with the I-PSS (p = 0.0001). The main reasons for not consulting were "a problem considered to be common at this age" (69.8%) and "fear of surgery" (47.7%). Following a clinical diagnosis of BPH, 93% of patients underwent complementary diagnostic investigations and 33.5% of them were referred to a urologist. A treatment decision (medical treatment in 83.5% of cases) was taken in 85.9% of cases, especially in older patients (p = 0.001) with higher I-PSS scores (p = 0.001). CONCLUSION: This epidemiological survey confirmed the difficulties of detection of BPH in general practice, as patients did not report any specific symptoms despite increasing discomfort. Management of the disease by general practitioners, following the diagnosis. complied with generally accepted clinical guidelines.

Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg).

Depot GnRH agonists are widely used for the treatment of precocious puberty. Leuprorelin 3-month depot is currently used in adults but has not been evaluated in children. We evaluated the efficacy of this new formulation (11.25 mg every 3 months), for the suppression of gonadotropic activation and pubertal signs in children with central precocious puberty. We included 44 children (40 girls) with early-onset pubertal development in a 6-month open trial. The inclusion criteria were clinical pubertal development before the age of 8 (girls) or 10 (boys), advanced bone age, enlarged uterus (>36 mm), testosterone more than 1.7 nmol/liter (boys), and pubertal response of LH to GnRH (peak >5 IU/liter). The principal criterion for efficacy assessment, GnRH-stimulated LH peak less than 3 IU/liter, was met in 81 of 85 (95%) of the tests performed at months 3 and 6. The remaining four values were slightly above the threshold. The levels of sex steroids were also significantly reduced and clinical pubertal development was arrested. Plasma leuprorelin levels, measured every 30 d, were essentially stable after d 60. Local intolerance was noted after 10 of 86 injections (12%), and was mild in four cases, moderate in five cases, and severe in one. Among these 10 events, 4 consisted in local pain at injection's site. In conclusion, leuprorelin 3-month depot efficiently inhibits the gonadotropic axis in 95% of children with central precocious puberty studied for a 6-month period. This regimen allows the reduction of the number of yearly injections from 12 to 4.