Abacavir usage patterns and hypersensitivity reactions in the EuroSIDA cohort.

OBJECTIVES: Five to eight per cent of HIV-positive individuals initiating abacavir (ABC) experience potentially fatal hypersensitivity reactions (HSRs). We sought to describe the proportion of individuals initiating ABC and to describe the incidence and factors associated with HSR among those prescribed ABC. METHODS: We calculated the proportion of EuroSIDA individuals receiving ABC-based combination antiretroviral therapy (cART) among those receiving cART after 1 January 2009. Poisson regression was used to identify demographic, and current clinical and laboratory factors associated with ABC utilization and discontinuation. RESULTS: Between 2009 and 2016, of 10 076 individuals receiving cART, 3472 (34%) had ever received ABC-based cART. Temporal trends of ABC utilization were also heterogeneous, with 28% using ABC in 2009, dropping to 26% in 2010 and increasing to 31% in 2016, and varied across regions and over time. Poisson models showed lower ABC utilization in older individuals, and in those with higher CD4 cell counts, higher cART lines, and prior AIDS. Higher ABC utilization was associated with higher HIV RNA and poor renal function, and was more common in Central-East and Eastern Europe and lowest during 2014. During 779 person-years of follow-up (PYFU) in 2139 individuals starting ABC after 1 January 2009, 113 discontinued ABC within 6 weeks of initiation for any reason [incidence rate (IR) 14.5 (95% confidence interval (CI) 12.1, 17.5) per 100 PYFU], 13 because of reported HSR [IR 0.3 (95% CI 0.1, 1.0) per 100 PYFU] and 35 because of reported HSR/any toxicity [IR 4.5 (95% CI 3.2, 6.3) per 100 PYFU]. There were no factors significantly associated with ABC discontinuation because of reported HSR/any toxicity. CONCLUSIONS: ABC remains commonly used across Europe and the incidence of discontinuation because of reported HSR was low in our study population.

A founding LRRK2 haplotype shared by Tunisian, US, European and Middle Eastern families with Parkinson's disease.

The Leucine-rich repeat kinase 2 (LRRK2) gene has been identified as a disease susceptibility gene for Parkinson's disease (PD), with G2019 (6055G>A) being the most frequent mutation. This mutation was present in 42% (38/91) of Tunisian families and 2% (1/39) of US families we have studied. A founding haplotype was identified in our data and it is shared by families from Tunisia, US, European and Middle Eastern countries. The most recent common founder of the mutation was dated to 2600 (95% CI: 1950-3850) years ago although additional studies are warranted to ensure an accurate age estimate for this mutation.

[The relationships between the general practitioner and the oncological radiotherapist. A preliminary study by telephone interviews]. / I rapporti tra medico generico e radioterapista oncologo. Studio preliminare attraverso interviste telefoniche.

PURPOSE: We addressed the issue of the relationship between the general practitioner (GP) and the radiotherapist to improve the quality of care of cancer patients. MATERIAL AND METHODS: The study consisted in evaluating medical requests and phone interviews, with a questionnaire with yes/no and multiple choice answers to the following 5 questions: 1) Do you think a cancer diagnosis is always a hopeless death sentence? 2) Is it professionally rewarding to cure a cancer patient? 3) Are you satisfied with your relationship, as a general practitioner, with oncologic reference centers? 4) Is it more wearing for a general practitioner to manage a cancer than a noncancer patient? 5) Would you answer a questionnaire about the relationship between the general practitioner, the cancer patient and the oncologist? We evaluated 1590 medical requests and made 401 phone interviews; 255 colleagues (70%) answered the questionnaire. RESULTS: Medical requests were correctly and completely formulated by GPs in 45% of cases. A cancer diagnosis was not considered a hopeless death sentence in 90.9% of cases and 76% of GPs considered it professionally rewarding to cure a cancer patient. 75.6% of GPs considered it more wearing to manage a cancer than a noncancer patient, and female GPs felt this more strongly than their male counterparts. Irrespective of gender, GPs over 50 years of age tend to consider cancer a hopeless and fatal disease. The relationship with oncologic centers was considered satisfactory in 86.2% of cases. However, since cancer patients need greater medical care, GPs would like a closer cooperation with oncologists. DISCUSSION AND CONCLUSIONS: The great interest GPs took in this study encourages further investigation through a more in depth questionnaire designed with the help of GPs themselves and interested statisticians.

Activators and inhibitors of the fibrinolytic system in maturity-onset diabetes mellitus without thromboembolic manifestations.

In patients with maturity-onset diabetes mellitus without thromboembolic manifestations, significant increases in both fibrinolytic and antifibrinolytic activity were demonstrated. The increased fibrinolytic activity observed under basal conditions could be due to the continuous release of plasminogen activators from damaged endothelial cells. This hypothesis is supported by the fact that the higher fibrinolytic activity observed in diabetics is followed by a lesser increase in fibrinolytic activity than in controls after the venous occlusion test. The main antiplasmins, except alpha 2-antiplasmin, were significantly higher in diabetics, and their levels were not affected by sex, metabolic regulation, retinopathy, duration of the disease or cholesterolemia. On the contrary, weight, therapy and triglyceridemia significantly influenced the levels of some antiplasmins. Furthermore, hypertriglyceridemia and hypercholesterolemia were associated with a reduction of fibrinolysis. Thus, these conditions may further increase the risk of thromboembolic complications of diabetes mellitus.