Is the time in therapeutic range on coumarins predicted by previous time in therapeutic range?

Background The benefit of vitamin K antagonists depends on the time within the therapeutic range (TTR). A patient's previous TTR could be a factor in the decision to change the anticoagulation regimen. However, the predictive value of a previous TTR for a future TTR is not well established, nor is it clear which TTR should prompt action. Objectives To investigate the predictive performance of a TTR and identify a threshold below which no recovery of TTR should be expected. Patients/Methods From 18 031 patients who used acenocoumarol in a first-line anticoagulation clinic, a TTR was calculated over multiple periods of 90, 180, and 365 days each. We assessed the correlation between baseline and later TTR and the separation between groups by quintile of baseline TTR. We describe the proportion of patients who obtain a TTR >= 70% conditional on baseline TTR. Results The correlation between baseline and later TTR was 0.25 (95% confidence interval [CI], 0.24-0.26), 0.27 (95% CI, 0.26-0.28) and 0.34 (95% CI, 0.32-0.35) for analyses over 90, 180, and 365 days. Corresponding c statistics for discrimination by baseline group were 0.60, 0.61, and 0.63. The probability to obtain a TTR >= 70% increased with baseline TTR: from 42% with a baseline TTR of 50%-65% when TTR was 100% (TTR calculated over 180 days). Conclusions We conclude that a current TTR hardly predicts a future TTR. Physicians and patients should deliberate together which probabilities to accept, take measures to improve TTR, and consider potential alternatives

Switching from acenocoumarol to phenprocoumon:step in personalised anticoagulation?

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.</p

Quality of life after switching from well-controlled vitamin K antagonist to direct oral anticoagulant:Little to GAInN

BACKGROUND: Direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) prevent thromboembolism in atrial fibrillation (AF). DOAC have a fixed dosing regimen and obviate INR monitoring. Therefore, DOAC presumably affect quality of life (QoL) less than VKA. However, some VKA users appreciate the monitoring. A high time in the therapeutic range (TTR) leads to a lower impact on QoL. We assessed the influence of switching from well-controlled VKA to a DOAC on QoL. METHODS: In the GAInN study, 241 patients with AF, a TTR ≥ 70%, and neither bleeding nor thrombosis while on VKA were randomised to switching to DOAC (n = 121) or continuing VKA (n = 120). Health-related (SF-36) and anticoagulation-related QoL (PACT-Q) was assessed at baseline and after six and twelve months of follow-up. RESULTS AND CONCLUSION: SF-36 development did not differ between groups. After one year, average PACT-Q Convenience improvement was 2.5 (0.3-4.7) higher on DOAC. DOAC users were 6percentage points (95%CI -4-16) more likely to improve >5 points on Convenience; 22 pp. (95%CI 1-43) in patients who scored <95/100 at baseline. The probability to meaningfully improve on PACT-Q Satisfaction was 12 pp. (95%CI 0-25) higher on DOAC. However, 5 (4.1%) and 4 (3.3%) DOAC users resumed VKA because of side-effects and patient preference. Switching from well-controlled VKA to DOAC for AF leads to a higher probability of improved PACT-Q convenience and satisfaction, but also to a higher risk of side-effects. Arguably only patients who are not satisfied with VKA should switch, because they have more to gain by switching

Effect of switching from acenocoumarol to phenprocoumon on time in therapeutic range and INR variability:A cohort study

BACKGROUND: Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control. AIMS: We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability. METHODS AND RESULTS: In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'. CONCLUSION: Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase

Influence of endotoxin induced fever on the pharmacokinetics of intramuscularly administered cefepime in rabbits

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 × 108 colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1–. There was a significant reduction in the elimination half-life by 21.8% in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9%, the mean residence time by 19.9%, the area under the plasma-concentration-time curve by 53.6% and the area under the moment curve by 62.3%. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits

Field testing two existing, standardized respiratory severity scores (LIBSS and ReSViNET) in infants presenting with acute respiratory illness to tertiary hospitals in Rwanda - a validation and inter-rater reliability study.

INTRODUCTION: There is a substantial burden of respiratory disease in infants in the sub-Saharan Africa region. Many health care providers (HCPs) that initially receive infants with respiratory distress may not be adequately skilled to differentiate between mild, moderate and severe respiratory symptoms, which may contribute to poor management and outcome. Therefore, respiratory severity scores have the potential to contributing to address this gap. OBJECTIVES: to field-test the use of two existing standardized bronchiolitis severity scores (LIBSS and ReSViNET) in a population of Rwandan infants (1-12 months) presenting with respiratory illnesses to urban, tertiary, pediatric hospitals and to assess the severity of respiratory distress in these infants and the treatments used. METHODS: A cross-sectional, validation study, was conducted in four tertiary hospitals in Rwanda. Infants presenting with difficulty in breathing were included. The LIBSS and ReSViNET scores were independently employed by nurses and residents to assess the severity of disease in each infant. RESULTS: 100 infants were recruited with a mean age of seven months. Infants presented with pneumonia (n = 51), bronchiolitis (n = 36) and other infectious respiratory illnesses (n = 13). Thirty-three infants had severe disease and survival was 94% using nurse applied LIBSS. Regarding inter-rater reliability, the intra-class correlation coefficient (ICC) for LIBSS and ReSViNET between nurses and residents was 0.985 (95% CI: 0.98-0.99) and 0.980 (0.97-0.99). The convergent validity (Pearson's correlation) between LIBSS and ReSViNET for nurses and residents was R = 0.836 (p<0.001) and R = 0.815 (p<0.001). The area under the Receiver Operator Curve (aROC) for admission to PICU or HDU was 0.956 (CI: 0.92-0.99, p<0.001) and 0.880 (CI: 0.80-0.96, p<0.001) for nurse completed LIBSS and ReSViNET respectively. CONCLUSION: LIBSS and ReSViNET were designed for infants with bronchiolitis in resource-rich settings. Both LIBSS and ReSViNET demonstrated good reliability and validity results, in this cohort of patients presenting to tertiary level hospitals. This early data demonstrate that these two scores have the potential to be used in conjunction with clinical reasoning to identify infants at increased risk of clinical deterioration and allow timely admission, treatment escalation and therefore support resource allocation in Rwanda