Time in Therapeutic Range of Oral Vitamin K Antagonists in Hospitalized Elderly Patients.

BACKGROUND: Oral vitamin K antagonists (VKAs) are commonly used in older adults. To ensure the efficiency and safety of these drugs, the international normalized ratio (INR) must be monitored. The time in therapeutic range (TTR) is an internationally recommended assessment of the anticoagulation quality. OBJECTIVE: Our study aimed to assess the TTR of VKAs in a hospitalized geriatric population and identify factors associated with low TTR. METHODS: This was a multicenter retrospective study of data from 1899 patients with a mean age of 87 years between 2013 and 2015 in the geriatric units of four French hospitals. The data collection consisted of 2450 VKA prescriptions. We excluded prescriptions with a duration of < 7 days, monitoring with fewer than two INR values and patients with prosthetic heart valves. TTR was assessed using the Rosendaal method. Factors associated with a low TTR (< 50%) were assessed using a non-parametric method. RESULTS: The mean TTR observed in this population was 42.6%. The TTR was < 50% for 62.5% of the patients included in this study. Significant associations were found between TTR < 50% and aspartate transaminase (AST), alkaline phosphatase (ALT), thyroid-stimulating hormone (TSH), prescription duration, fluconazole instauration, hemoglobin, and C-reactive protein (CRP). CONCLUSIONS: Both our results and those in the literature indicate that TTR in geriatric populations is lower than that in the general population. Most patients had an insufficient TTR, exposing them to an increased risk of thromboembolic and hemorrhagic events. These data provide a perspective on poor-quality anticoagulation and illustrates the difficulty of using VKAs in geriatric patients.

[Emergent adverse effects of proton pump inhibitors]. / Effets indésirables émergents des inhibiteurs de la pompe à protons.

BACKGROUND: Recent literature reports of potential adverse effects (AEs) of proton pump inhibitors (PPIs), especially during long-term treatments. PURPOSE: To present a literature review of major AEs: digestive infections, pneumonia, bone fracture, hypomagnesemia, interstitial nephritis, gastric cancer and neutropenia. DATA SOURCES: The authors used Pubmed; articles in English or French, published between August 2006 and August 2011 were analyzed. STUDY SELECTION: Two reviewers analyzed the references of title and summary to retain mainly observational studies, controlled clinical trials, meta-analyzes, case reports. RESULTS: For digestive infections: observational studies have shown a link moderate to high (OR 1.4 to 8.3) with exposure to PPIs. For pneumonia: some case-control studies reported a modest significative risk (OR 1.2 to 1.6), some not. The risk appears dose dependent and greater in subjects at risk. For fractures: the majority of observational studies report a significative increase in low to moderate risk (OR 1.2 to 3.1), correlated with the dose and duration of treatment. For magnesium deficiency: rare but potentially severe, they are described in case reports. Interstitial nephritis are described in case reports and for different PPIs, suggesting a class effect. For the stomach neoplasm: if three observational studies show an increased cancer risk (OR 1.5 to 2, 3), confounding factors make the causal link uncertain. Neutropenia is reported in a clinical observation, a class effect is suggested. LIMITATIONS: One can regret the absence of controlled clinical trials; indeed the observational studies have the interest to move closer to "real life", but often have methodological bias. CONCLUSION: Although AEs PPIs do not call into question the usefulness of this drug class, they show the need to limit their prescribing to indications for which efficacy has been proven. Moreover, PPIs treatment must be regularly reassessed to avoid exposing patients to unnecessary risks.

Comparison of four renal function estimation equations for pharmacokinetic modeling of gentamicin in geriatric patients.

Most aminoglycoside pharmacokinetic models include an index of renal function, such as creatinine clearance, to describe drug clearance. However, the best clinical descriptor of renal function for the pharmacokinetic modeling of aminoglycosides has not been established. This analysis was based on 412 gentamicin concentrations from 92 geriatric patients who received intravenous gentamicin for various infectious diseases. Four two-compartment population models were fitted to gentamicin concentrations in a learning set of 64 patients using the nonparametric adaptive grid (NPAG) algorithm. Each model included an index of renal function, namely, the Cockcroft-Gault (CG), Jelliffe (JEL), modification of diet in renal disease (MDRD), or modified MDRD (MDRDm; adjusted to individual body surface area) equation as a covariate influencing gentamicin serum clearance. Goodness of fit and predictive performance of the four models were compared using standard criteria in both the learning set and in a validation set of 28 patients. A final analysis was performed to estimate the population pharmacokinetic parameter values of the entire 92-patient group. In the learning set, the CG-based model best fit the data, followed by JEL-, MDRD-, and MDRDm-based models, with relative reductions of the Akaike information criterion of 29.4, 20.2, 14.2, and 4.2, respectively. Bias and precision of population predictions were significantly different among the four models. In the validation set, individual predictions from the four models showed marginally different biases. The final estimation confirmed the previous results. Specifically, the CG-based model showed predictive performance that was comparable to or better than that of the MDRD-based model at each stage of the analysis. This study shows that methods used to estimate renal function should not be considered interchangeable for the model-based estimation of gentamicin concentrations.