29 research outputs found
Insulin-Like Growth Factor-1 but Not Insulin Predicts Cognitive Decline in Huntington's Disease
BACKGROUND: Huntington\u27s disease (HD) is one of several neurodegenerative disorders that have been associated with metabolic alterations. Changes in Insulin Growth Factor 1 (IGF-1) and/or insulin input to the brain may underlie or contribute to the progress of neurodegenerative processes. Here, we investigated the association over time between changes in plasma levels of IGF-1 and insulin and the cognitive decline in HD patients.
METHODS: We conducted a multicentric cohort study in 156 patients with genetically documented HD aged from 22 to 80 years. Among them, 146 patients were assessed at least twice with a follow-up of 3.5 ± 1.8 years. We assessed their cognitive decline using the Unified Huntington\u27s Disease Rating Scale, and their IGF-1 and insulin plasmatic levels, at baseline and once a year during the follow-up. Associations were evaluated using a mixed-effect linear model.
RESULTS: In the cross-sectional analysis at baseline, higher levels of IGF-1 and insulin were associated with lower cognitive scores and thus with a higher degree of cognitive impairment. In the longitudinal analysis, the decrease of all cognitive scores, except the Stroop interference, was associated with the IGF-1 level over time but not of insulin.
CONCLUSIONS: IGF-1 levels, unlike insulin, predict the decline of cognitive function in HD
Effectiveness of anti-psychotics and related drugs in the Huntington French-speaking group cohort.
PURPOSE: Huntington's disease is a rare condition. Patients are commonly treated with antipsychotics and tetrabenazine. The evidence of their effect on disease progression is limited and no comparative study between these drugs has been conducted. We therefore compared the effectiveness of antipsychotics on disease progression.
METHODS: 956 patients from the Huntington French Speaking Group were followed for up to 8 years between 2002 and 2010. The effectiveness of treatments was assessed using Unified Huntington's Disease Rating Scale (UHDRS) scores and then compared using a mixed model adjusted on a multiple propensity score.
RESULTS: 63% of patients were treated with antipsychotics during the survey period. The most commonly prescribed medications were dibenzodiazepines (38%), risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no difference between treatments on the motor and behavioural declines observed, after taking the patient profiles at the start of the drug prescription into account. In contrast, the functional decline was lower in the dibenzodiazepine group than the other antipsychotic groups (Total Functional Capacity: 0.41 ± 0.17 units per year vs. risperidone and 0.54 ± 0.19 vs. tetrabenazine, both p<0.05). Benzamides were less effective than other antipsychotics on cognitive evolution (Stroop interference, Stroop color and Literal fluency: p<0.05).
CONCLUSIONS: Antipsychotics are widely used to treat patients with Huntington's disease. Although differences in motor or behavioural profiles between patients according to the antipsychotics used were small, there were differences in drug effectiveness on the evolution of functional and cognitive scores
Guidelines for clinical pharmacological practices in Huntington's disease
OBJECTIVE: Evidence-based medicine is a difficult goal to achieve in rare diseases where randomized controlled trials are lacking. This report provides guidelines that capitalize on both the literature and expertise of the French National Huntington Disease Reference Centre to optimalize pharmacological therapeutic interventions for Huntington\u27s disease (HD).
MATERIAL AND METHODS: HD experts conducted a systematic analysis of the literature from 1965 to 2013, using a scoring procedure established by the French National Authority for Health. These experts offered their views when evidence was missing to set up provisional guidelines for care in HD. These guidelines were then scored and amended through two subsequent online questionnaires (using SurveyMonkey scoring), and one face-to-face meeting with an external multidisciplinary working group as a step towards validation.
RESULTS: Except for the beneficial effects of tetrabenazine in chorea, none of the published recommendations were grounded on established scientific evidence. Second-generation antipsychotics are nevertheless the first choice for patients with psychiatric manifestations (low level of evidence). All other guidelines are based on low-level evidence and little professional agreement.
CONCLUSION: Patients\u27 care has greatly improved over the last few years despite the lack of high-level evidence standards. Guidelines are based on the expertise of trained specialists from the French National Plan for Rare Diseases. This strategy should now be extended internationally to promote future studies and to harmonize worldwide care of HD
Survival and treatment patterns of patients with relapsed or refractory multiple myeloma in France â a cohort study using the French National Healthcare database (SNDS)
International audienceAbstract Over the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database (SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide. Data were analyzed overall, by first-line (1L) autologous stem cell transplant (ASCT) status and by lenalidomide treatment status at 2L. In total, 12987 patients with RRMM were included in the study (mean age 69.5 years); 27% received an ASCT at 1L, and 30% received a lenalidomide-sparing regimen at 2L. Overall, and among the ASCT and non-ASCT subgroups, most patients received a bortezomib-based regimen at 1L, whereas lenalidomide-based regimens were most common at 2L. Among patients who received a lenalidomide-sparing regimen at 2L, this was most often a proteasome inhibitor-based regimen. Mortality rate was 26.1/100 person-years, and median (95% confidence interval) survival from 2L initiation was 32.4 (31.2â33.6) months. Survival differed by various factors, shorter survival was reported in the non-ASCT group, those receiving a lenalidomide-sparing regimen at 2L, older patients (â„ 70 years), and those with multiple comorbidities. This analysis provides insight into the real-world use of approved novel MM treatments and highlights an ongoing unmet need to improve outcomes, particularly for selected patient groups
Guidelines for clinical pharmacological practices in Huntington's disease.
International audienceOBJECTIVE: Evidence-based medicine is a difficult goal to achieve in rare diseases where randomized controlled trials are lacking. This report provides guidelines that capitalize on both the literature and expertise of the French National Huntington Disease Reference Centre to optimalize pharmacological therapeutic interventions for Huntington's disease (HD).MATERIAL AND METHODS: HD experts conducted a systematic analysis of the literature from 1965 to 2013, using a scoring procedure established by the French National Authority for Health. These experts offered their views when evidence was missing to set up provisional guidelines for care in HD. These guidelines were then scored and amended through two subsequent online questionnaires (using SurveyMonkey scoring), and one face-to-face meeting with an external multidisciplinary working group as a step towards validation.RESULTS: Except for the beneficial effects of tetrabenazine in chorea, none of the published recommendations were grounded on established scientific evidence. Second-generation antipsychotics are nevertheless the first choice for patients with psychiatric manifestations (low level of evidence). All other guidelines are based on low-level evidence and little professional agreement.CONCLUSION: Patients' care has greatly improved over the last few years despite the lack of high-level evidence standards. Guidelines are based on the expertise of trained specialists from the French National Plan for Rare Diseases. This strategy should now be extended internationally to promote future studies and to harmonize worldwide care of HD.</p
DĂ©pistage et traitement de lâhypercholestĂ©rolĂ©mie familiale chez des patients suivis en ambulatoire : Ă©tude longitudinale rĂ©trospective
RealâWorld Effectiveness of Osteoporosis Medications in France: A Nationwide Cohort Study
ABSTRACT Although drugs for osteoporosis have been demonstrated to be effective in reducing fracture risk in placeboâcontrolled clinical trials, data on effectiveness in realâworld practice is limited. Data from the French national health insurance claims database (SNDS) were used to follow five cohorts of women aged â„55âyears after initiating treatment for â„6âmonths with either denosumab, zoledronic acid, oral bisphosphonates, raloxifene, or teriparatide in 2014â2016. Fracture incidence was compared within each cohort between the 3 months following initiation (baseline fracture risk) and the 12month, 18month, and 24 month postinitiation periods. Data are presented as incidence rate ratios (IRRs) with their 95% confidence intervals (CIs)s. Overall, 67,046 women were included in the denosumab cohort, 52,914 in the oral bisphosphonate cohort, 41,700 in the zoledronic acid cohort, 11,600 in the raloxifene cohort, and 7510 in the teriparatide cohort. The baseline vertebral fracture rate ranged from 1.74 per 1000 person years (â°PY) in the raloxifene cohort to 34.75â°PY in the teriparatide cohort, and the baseline hip fracture rate from 0.70â°PY in the raloxifene cohort to 10.52â°PY in the zoledronic acid cohort. Compared with the baseline fracture rate, vertebral fractures involving hospitalization were significantly reduced in the 3â24âmonth postinitiation period with denosumab (IRR 0.6; 95% CI, 0.5â0.7), zoledronic acid (IRR 0.4; 95% CI, 0.3â0.4), teriparatide (IRR 0.3; 95% CI, 0.2â0.5), and oral bisphosphonates (IRR 0.6; 95% CI, 0.4â0.8). Hip fracture incidence was reduced with denosumab (IRR 0.8; 95% CI, 0.6â0.9), but higher for oral bisphosphonates (IRR 1.7; 95% CI, 1.2â2.3); no significant change in hip fracture rate was observed for zoledronic acid, teriparatide, or raloxifene. A reduction in nonvertebral, nonâhip fracture incidence was observed only in the denosumab cohort (IRR 0.8; 95% CI, 0.7â0.9). These findings indicate that treatment with osteoporosis drugs is effective in the realâworld setting. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research