Abstract
The interpretation of long-acting cabotegravir and rilpivirine concentrations is complicated by the lack of consensus on the threshold to consider. Building on real-world therapeutic drug ...monitoring data and documented virologic failures, this article provides a reappraisal of the existing thresholds and guidance for the interpretation of cabotegravir and rilpivirine concentrations.
There is no established threshold for the interpretation of long-acting cabotegravir/rilpivirine concentrations. Building on real-world TDM data and documented virologic failures, this article provides a reappraisal of the existing thresholds, and guidance for the interpretation of cabotegravir and rilpivirine concentrations.
Patient-Reported Outcomes (PRO) integrate a wide range of holistic dimensions that arenot captured within clinical outcomes. Particularly, from induction treatment to maintenance therapy, patient ...quality-of-life (QoL) of kidney transplant recipients have been sparsely investigated in international settings.
In a prospective, multi-centric cohort study, including nine transplant centers in four countries, we explored the QoL during the year following transplantation using validated elicitation instruments (EQ-5D-3L index with VAS) in a population of kidney transplant patients receiving immunosuppressive therapies. Calcineurin inhibitors (tacrolimus and ciclosporin), IMPD inhibitor (mycophenolate mofetil), and mTOR inhibitors (everolimus and sirolimus) were the standard-of-care (SOC) medications, together with tapering glucocorticoid therapy. We used EQ-5D and VAS data as QoL measures alongside descriptive statistics at inclusion, per country and hospital center. We computed the proportions of patients with different immunosuppressive therapy patterns, and using bivariate and multivariate analyses, assessed the variations of EQ-5D and VAS between baseline (i.e., inclusion Month 0) and follow up visits (Month 12).
Among 542 kidney transplant patients included and followed from November 2018 to June 2021, 491 filled at least one QoL questionnaire at least at baseline (Month 0). The majority of patients in all countries received tacrolimus and mycophenolate mofetil, ranging from 90.0% in Switzerland and Spain to 95.8% in Germany. At M12, a significant proportion of patients switched immunosuppressive drugs, with proportion varying from 20% in Germany to 40% in Spain and Switzerland. At visit M12, patients who kept SOC therapy had higher EQ-5D (by 8 percentage points,
< 0.05) and VAS (by 4 percentage points,
< 0.1) scores than switchers. VAS scores were generally lower than EQ-5D (mean 0.68 0.5-0.8 vs. 0.85 0.8-1).
Although overall a positive trend in QoL was observed, the formal analyses did not show any significant improvements in EQ-5D scores or VAS. Only when the effect of a therapy use was separated from the effect of switching, the VAS score was significantly worse for switchers during the follow up period, irrespective of the therapy type. If adjusted for patient characteristics and medical history (e.g., gender, BMI, eGRF, history of diabetes), VAS and EQ-5D delivered sound PRO measures for QoL assessments during the year following renal transplantation.
Aims To assess the associations of exposure and modifications in exposure (i.e., discontinuation on admission, initiation during hospitalization) to eight common cardiovascular therapies with the ...risk of in-hospital death among inpatients with coronavirus disease 2019 (COVID-19). Methods In this observational study including 838 hospitalized unvaccinated adult patients with confirmed COVID-19, the use of cardiovascular therapies was assessed using logistic regression models adjusted for potential confounders. Results No cardiovascular therapy used before hospitalization was associated with an increased risk of in-hospital death. During hospitalization, the use of diuretics (aOR 2.59 1.68–3.98) was associated with an increase, and the use of agents acting on the renin-angiotensin system (aOR 0.39 0.23–0.64) and lipid-lowering agents (aOR 0.41 0.24–0.68) was associated with a reduction in the odds of in-hospital death. Exposure modifications associated with decreased survival were the discontinuation of an agent acting on the renin-angiotensin system (aOR 4.42 2.08–9.37), a β-blocker (aOR 5.44 1.16–25.46), a lipid-modifying agent (aOR 3.26 1.42–7.50) or an anticoagulant (aOR 5.85 1.25–27.27), as well as the initiation of a diuretic (aOR 5.19 2.98–9.03) or an antiarrhythmic (aOR 6.62 2.07–21.15). Exposure modification associated with improved survival was the initiation of an agent acting on the renin-angiotensin system (aOR 0.17 0.03–0.82). Conclusion In hospitalized and unvaccinated patients with COVID-19, there was no detrimental association of the prehospital use of any regular cardiovascular medication with in-hospital death, and these therapies should be continued as recommended.
Poncet A, Gencer B, Blondon M, Gex-Fabry M, Combescure C, Shah D, et al. (2015) Electrocardiographic Screening for Prolonged QT Interval to Reduce Sudden Cardiac Death in Psychiatric Patients: A ...Cost-Effectiveness Analysis.
...the TdP-related mortality and TdP avoidance parameters were varied in a 2-way sensitivity analysis to assess their effect on the incremental cost-effectiveness ratio (ICER).
The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with ...an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported.
SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023.
Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p < 0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load.
Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated.
This work was funded by the Swiss National Science Foundation, grant number N
324730_192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers).
Aims
The aim of this study was to assess the cost-effectiveness of eight common diagnostic work-up strategies for coronary heart disease (CHD) in patients with stable angina symptoms in Switzerland.
...Methods and results
A decision analytical model was used to perform a cost-effectiveness comparison of eight common multitest strategies to diagnose CHD using combinations of four diagnostic techniques: exercise treadmill test (ETT), single-photon emission computed tomography (SPECT), cardiac magnetic resonance imaging (CMR), and coronary angiography (CA). We used a Markov state transition model to extrapolate the results over a life-time horizon, from a third-party payer perspective. We used a CHD prevalence rate of 39% in patients and a base-case scenario with 60-year-old male patients with intermediate symptom severity Canadian Cardiovascular Society grading of angina pectoris 2 and at least one cardiovascular (CV) risk factor but without a history of myocardial infarction and without need for revascularization. Among the eight work-up strategies, one strategy was dominant, i.e. least costly and most effective: ETT followed by CMR if the ETT result was inconclusive and then CA if the CMR result was positive or inconclusive. The CMR features a favourable balance between false-negative diagnoses, associated with an elevated risk of CV events, and false-positive diagnoses, leading to unnecessary CA and related mortality. Key parameters guiding the diagnostic strategy are the prevalence of CHD in patients with angina symptoms and the diagnostic costs of CA and CMR.
Conclusion
Cardiac magnetic resonance imaging appears to be a cost-effective work-up strategy compared with other regimens using SPECT or direct CA. Cardiac magnetic resonance imaging should be more widely recommended as a diagnostic procedure for patients with suspected angina symptoms.
The list of drugs whose abrupt discontinuation is likely to induce withdrawal symptoms or a rebound in the pathology being treated is not limited to psychotropic drugs. It includes a number of ...somatic drugs (e.g. proton pump inhibitors, opioids, triptans, fingolimod, corticosteroids, antiepileptics, nootropics, antiparkinsonians, denosumab, beta-blockers, laxatives, nasal vasoconstrictors, etc.). This type of unintended effect, often underestimated, generally results from a drug-induced homeostatic imbalance that persists after the drug has been discontinued. Taking this risk into account right from the initial prescription should make it possible to prevent such complications, by encouraging intermittent use of the drug, or by applying a very gradual reduction in dosage when a regular treatment is stopped.
PDF
