Recent case reports of 'sleep attacks' (SA) in patients with Parkinson's disease (PD) generated concerns about drug-induced daytime somnolence in this population. However, there are nearly no comparative data on sleep and vigilance problems between PD patients and normal controls. We performed a cross-sectional survey in PD patients and age-matched controls using a structured questionnaire on PD history, treatments, co-morbidity, activities of daily living, habits, exercise, sleep pattern, driving, pre-existing nocturnal problems, daytime somnolence, episodes of SA and the circumstances in which such episodes occurred. Daytime somnolence was also measured with the Epworth Sleepiness Scale (ESS) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). 176 PD patients and 174 controls were included. The same proportion of PD patients (27%) and controls (32%) reported episodes of SA, but these were more frequent in PD patients and occurred more frequently during situations requiring attention (10.8% vs. 1.7%, p<10(-3)). More PD patients had abnormal daytime somnolence (ESS) and poor sleeping quality (PSQI). The most consistent factor associated with SA was the duration of levodopa therapy and the predictive value of an abnormal ESS score was rather poor (40.7%). Abnormal daytime somnolence and poor sleep quality at night are more frequent in PD patients than in normals. However, SA are reported in both groups, although less frequently in the normals during activities that requires attention.

AimsThere is evidence that different methods used to identify and quantify adverse drug reactions (ADR) in hospitals are not exhaustive (spontaneous repor ting or computerized medical databases). The combination of these different sources of data could improve knowledge about ADR frequency in hospitals. The aim of this study was to estimate the incidence of serious ADRs handled in medical wards of a French university hospital using data from the Programme de Medicalization des Systemes d'Information (PMSI) and spontaneous reports recorded in the French Pharmacovigilance Database. MethodsThe study period was the first semester of 2001. From PMSI, all hospitalization summaries including an ICD-10th code related to a potential ADR were selected. From the French Pharmacovigilance Database, all serious ADRs which occurred during the study period and were reported by physicians working in the University Hospital were collected. After identification of common cases, the capture-recapture method was applied in order to estimate the real number of ADRs occurring during the fi rst semester of 2001. ResultsFrom PMSI, we identified 274 different hospital stays related to an ADR. Out of 241 reports selected from the French Pharmacovigilance Database, we retained 151 ADRs for analysis. Fifty-two ADRs were common in the two databases, g iving an estimated number of serious ADRs of 796 [95% confidence interval (CI) 638, 954], corresponding to 2.9% of inpatients (95% CI 2.3, 3.5).

The effectiveness of spa therapy in the management of patients with Parkinson's disease (PD) has never been evaluated. This is assessed in this pilot study. A prospective, randomized, cross-over, controlled study was conducted in 31 PD patients who underwent a 20-week spa period, including spa therapy for 3 weeks, and a 20-week non-spa period. Effectiveness was assessed using quality of life scales (PDQ-39 and SF-36), motor scale (UPDRS) and psychological questionnaire (GHQ-28), at baseline and at 4 (T4) and at 20 weeks (T20). Direct medical costs (radiological and laboratory tests, physician fees, drug therapy, and ancillary care) were recorded over each 20-week period. At T4, spa therapy improved significantly several dimensions of PDQ-39 and SF-36, part IV of the UPDRS, and GHQ-28. At T20, no difference in any parameter was found. The mean direct medical cost over 20 weeks (euro;1,328 +/- 167; pound 776 +/- 97 per patient) in the spa period was slightly but significantly reduced in comparison with that of the non-spa period (euro;1380 +/- 523; pound 807 +/- 306 per patient). This cost-effectiveness analysis suggests that spa therapy is more effective and less expensive than conventional treatment alone and could be beneficial in the management of PD.

The present pharmacoepidemiologic study was performed to characterize the profile of adverse drug reactions (ADRs) reported with selegiline, a monoamine oxidase B (MAO-B) inhibitor used in the treatment of Parkinson's disease and previously reported to induce an excess of mortality. The analysis was performed with use of the French Pharmacovigilance Database between 1989 and 1997. This database includes all ADRs reported by French practitioners (and especially "serious" and "unexpected" ADRs). Three different analyses were performed: identification of ADRs reported with selegiline, comparison with the ADR profile observed with other antiparkinsonian drugs, and a case/non-case study investigating the occurrence of cardiovascular ADRs with selegiline in comparison with other drugs in general and other antiparkinsonian drugs (e.g., levodopa [L-Dopa], dopamine agonists) in particular. The most often reported ADRs with selegiline were psychiatric (delirium, hallucinations, agitations), cardiovascular (orthostatic hypotension, arterial hypertension, etc.) and neurologic (sedation, abnormal movements, etc.). Psychiatric and cardiovascular ADRs were more frequently reported with selegiline than with L-Dopa or dopamine agonists. The case/ non-case study found an increased risk of cardiovascular ADRs (OR = 1.72; 95% Cl = 1.16-2.55)when selegiline was associated with L-Dopa. These data show that the profile of selegiline-induced ADRs differs from that of other antiparkinsonian drugs (L-Dopa, dopamine agonists) with more psychiatric and cardiovascular ADRs. We suggest that the higher frequency of cardiovascular ADRs could explain, at least partially, the previously reported increase in mortality rate.

The present paper compares, in terms of mortality, two treatment regimens for Parkinson's disease (PD), i.e., bromocriptine later combined with levodopa versus levodopa only. Between 1982 and 1989, 60 PD patients (29 treated with levodopa alone [group D] and 31 receiving first bromocriptine followed by an association of bromocriptine + levodopa [group B/D]) were recruited. Data were updated in January 2000. Survival functions were estimated using Kaplan Meier product-limit method and comparison between the two groups with the log-rank test. Mortality was also compared with that of the general French population using standardized mortality ratios (SMRs). The mean duration of follow-up was 10.3 +/- 3.0 years. Seventeen patients died during the follow-up: nine in the group B/D and eight in the group D. The probability of survival at 10 years was 79.0% [95% confidence interval [CI]: 71.4-86.6] in group B/D and 72.9% [95% CI: 63.3-82.6] in group D. In comparison with the general French population, SMRs were not statistically different from 1, in the whole sample of PD patients (1.21, 95 % CI [0.71-1.95]), in group D (0.98 [0.42-1.93]), or in group B/D (1.53 [0.70-2.92]). In this population, we were unable to find any favourable effect of an early use of bromocriptine on mortality in PD in comparison with levodopa alone.

Introduction: Population-based studies using health insurance databases are very useful for epidemiological studies, notably for rare diseases such as immune thrombocytopenia (ITP). French health insurance databases, called SNIIRAM (Système d'Information Inter-Régimes de l'Assurance Maladie) cover the entire French population (66 million inhabitants).We developed an algorithm that identifies incident primary ITP cases in the SNIIRAM. The aim of this study was to evaluate the positive predictive value (PPV) of this algorithm. Methods: The SNIIRAM is an electronic database prospectively recording demographic, hospitalization, long term disabling disease (LTD) and out-hospital drugs dispensing as well as other healthcare data. The algorithm used to identify newly diagnosed primary ITP patients follows several steps: 1) extraction of patients with at least one ITP code (D69.3 code of the International Classification of Disease, version 10 -ICD-10) as primary diagnosis during a hospital stay or as LTD; 2) exclusion of patients with ambiguous or contradictory codes, i.e.other D69 ICD-10 codes as LTD or hospital diagnosis between 12 months before and 6 months after the first ITP code, except D69.6 (thrombocytopenia, unspecified) and D69.9 (hemorrhagic condition, unspecified); 3) refining of the presumed date of diagnosis searching ITP drug dispensing in the six-month period before the first ITP code. A six-month wash out period is used to define incident ITP; 4) lastly, secondary ITPs are defined by a LTD or a hospitalization with codes corresponding to hematological malignancies, chronic viral infections and connective tissue diseases between 12 months before and 6 months after the presumed date of diagnosis. For the present validation study, we applied this algorithm to regional SNIIRAM data of the Midi-Pyrénées region (South of France, 3 million inhabitants) to identify incident ITP patients between July 1, 2012 and June 30, 2014. Medical charts were independently reviewed by two investigators. We calculated the PPVs of: 1) the diagnosis of ITP; 2) the fact that ITP was incident or not (compared with the true date of diagnosis and the true date of first ITP symptoms); 3) the identification of secondary ITPs. Results: We identified 200 incident ITP patients in the Midi-Pyrénées regional SNIIRAM during the study period. We could assess by medical chart review 168 cases. At ITP diagnosis, 70.4% of the patients were adults (≥18 years). Median age was 2.8 years in children and 63.0 years in adults. The male:female sex-ratio was 0.83. Overall, 66.6% of the patients had bleeding symptoms. The median platelet count was 10 x 109/L. After medical chart review, 161 cases were true ITP yielding a PPV of 95.8% (95% confidence interval - 95% CI: 92.8-98.8). Among them, 128 were incident according to the date of symptom onset and 134 were incident according to the true diagnosis date yielding PPVs of 79.5% (95% CI: 73.2-85.7) and 83.2% (95% CI: 77.4-89.0), respectively. As expected, the PPV for newly diagnosed ITP was significantly lower in case of low platelet count as first symptom compared tobleeding revealing ITP (respectively, 65.4%, 95% CI: 52.5-78.3 and 92%, 95% CI 86.9-97.0, p=0.08). The median time from the date of first symptoms and the estimated date of ITP onset by the algorithm was 3 days (interquartile range - IQR: 0 to 20). The median time from the true date of diagnosis and the estimated date of ITP diagnosis by the algorithm was 0 days (IQR: 0 to 15). Ten patients were identified as having a secondary ITP using the algorithm: 4 lymphoid neoplasms (2 B-cell lymphoma, 1 Hodgkin lymphoma and 1 chronic lymphoid leukemia), 4 connective tissue diseases (sarcoidosis, rheumatoid arthritis, systemic sclerosis and Sjögren syndrome, 1 case each) and 2 chronic infections (HIV and HCV). There was no misclassification after medical chart review. On the contrary, 7 secondary ITPs identified by medical chart review were not detected by the algorithm: 3 CMV and 1 EBV infections, 1 Waldenström disease, 1 plasmocytoma and 1 myelodysplastic syndrome. Conclusions: This algorithm showed good PPV in identifying incident primary ITP patients and could be extended to other similar databases. The estimated date of ITP onset may be delayed in case of isolated chronic thrombocytopenia because platelet count results are not recorded in the database. The SNIIRAM is not a useful database to detect virus-associated secondary ITP. Disclosures No relevant conflicts of interest to declare.

Our survey allowed us to identify the suspected drug-induced agranulocytosis through a prospective study in a large sample of inpatients using only laboratory data analysis. We also note an important underreporting rate of this serious adverse drug reaction (ADR) to the official French pharmacovigilance system. Laboratory data analysis could be used for identifying serious ADRs.

This study showed a very good PPV of this algorithm identifying incident primary ITP patients in the SNIIRAM.