Effects of Weekly Supplementation of Cholecalciferol and Calcifediol Among the Oldest-Old People: Findings From a Randomized Pragmatic Clinical Trial.

Vitamin D inadequacy is pervasive in the oldest-old. Many vitamin D metabolites are available for supplementation, their effects on the recovery of adequate serum levels remain unknown. We investigate the effects of supplementation with cholecalciferol (D3) and calcifediol (25D3) on serum levels of 25(OH)D, 1-25(OH)D, bone and inflammatory markers, ultimately identifying clinical predictors of successful treatment. Sixty-seven oldest-old individuals were randomized to weekly administration of 150 mcg of 25D3 or D3, from hospital admission to 7 months after discharge. Supplementation of 25D3 and D3 were associated with increasing serum levels of 25(OH)D (p < 0.001) and 1-25(OH)D (p = 0.01). Participants on 25D3 experienced a steeper rise than those on D3 (group*time interaction p = 0.01), after adjustment for intact parathyroid hormone (iPTH) levels the differences disappeared (intervention*iPTH interaction p = 0.04). Vitamin D supplementation was associated with a decreasing trend of iPTH and C-reactive protein (CRP) (p < 0.001). Polypharmacy and low handgrip strength were predictors of failure of intervention, independent of vitamin D metabolites. In conclusion, D3 and 25D3 supplementation significantly increase vitamin D serum levels in the oldest-old individuals, with a tendency of 25D3 to show a faster recovery of acceptable iPTH levels than D3. Polypharmacy and low muscle strength weaken the recovery of adequate vitamin D serum levels.

Prescribing patterns of allopurinol and febuxostat according to directives on the reimbursement criteria and clinical guidelines: analysis of a primary care database.

OBJECTIVE: According to American clinical guidelines, allopurinol and febuxostat may be prescribed as first-line therapy to treat hyperuricemia. However, the Italian Medicines Agency directive, called Nota 91, allows the reimbursement of second-line febuxostat in the case of failure and/or intolerance of a previous allopurinol therapy, so partially embracing European League Against Rheumatism recommendations and the British Society for Rheumatology Guideline. Such inconsistency might lead to heterogeneity among General Practitioners (GPs) in treatment of hyperuricemia. This study, therefore, aimed to evaluate the prescribing behavior of GPs in terms of compliance with Nota 91 and/or official guidelines. METHODS: Using the Health Search Database, a retrospective cohort study was conducted to evaluate the patterns of use of allopurinol and febuxostat between 2011 and 2016. RESULTS: In total, 44,257 and 5837 patients were prescribed with allopurinol and febuxostat, respectively. Among febuxostat users, 4321 (74%) had a previous allopurinol treatment; 92% of switches to febuxostat were related to hyperuricemia, whereas 9% of switchers presented intolerance to allopurinol; 26% of patients were prescribed with febuxostat as first-line therapy. The presence of diabetes and/or moderate/severe renal disease were statistically significant determinants of febuxostat use as first-line therapy. CONCLUSION: Prescriptions of febuxostat were highly compliant to Nota 91. Only a sub-group of frontline prescriptions of febuxostat were mainly driven by the presence of renal dysfunction, which is able to increase the risk of allopurinol intolerance and/or inefficacy. These findings indicate that GPs' prescribing behavior for hyperuricemia is highly compliant with both regulatory directives and clinical guidelines.

[Blood pressure: the lower the better? Maybe no]. / Pressione arteriosa: più bassa è, meglio è? Forse no.

Antihypertensive treatment is aimed at reducing as much as possible health outcomes in terms of morbidity and mortality. The main international guidelines and clinical trials showed different positions about blood pressure targets. At present, there is no common opinion about the benefits of an aggressive drug treatment; moreover it is not clear whether lower blood pressure values are related to increased morbidity and mortality. The recent randomized SPRINT trial has compared intensive vs standard drug therapy in a non-diabetic hypertensive population. The trial has shown benefits of intensive treatment in reducing important health outcomes, though results were not confirmed in several patient subsets. We examined the studies on hypertensive patients with comorbidities (i.e., chronic kidney disease, cardiovascular disease) to identify blood pressure targets recommended in these populations, but no strong evidence was found about the benefits of intensive treatment. In geriatric patients the "lower is better" paradigm cannot be entirely applied because of comorbidity, polypharmacy and frailty.