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Institute
We aimed to characterize non-oncologic chronic drug therapy of bladder cancer (BC) patients and evaluate a possible impact on recurrence-free (RFS) and cancer-specific survival (CSS). Patients with a first diagnosis (FD) of BC or radical cystectomy (RC) were included in a prospective, monocentric, observational study. Drugs and medical data was assessed at start and three-monthly for 24 months. Drugs were classified by anatomical-therapeutic-chemical code (ATC). Endpoints for outcome analysis were RFS and CSS in univariate (Kaplan–Meier curves and log-rank test, Cox regression for Hazard Ratio (HR)) and multivariate (Cox regression models) analyses. Of 113 patients, 52 had FD and 78 RC. Median age was 74 and 72 years, 83% and 82% were male. Drugs of 114 ATC classes were taken by 48 (92%) FD patients (median number 4.5/IQR 2–7.5) and 73 (94%) of RC patients (median 5/IQR 2–9). In univariate analysis (log-rank test (p)/Cox regression (HR, 95% CI, p)), polypharmacy (p = 0.036/HR = 2.83, 95% CI = 1.02–7.90, p = 0.047), calcium channel blockers (p = 0.046/HR = 2.47, 95% CI = 0.97–6.27, p = 0.057) and proton pump inhibitors (p = 0.015/HR = 3.16, 95% CI = 1.18–8.41, p = 0.022) had a significant negative impact on RFS in RC patients, statins (p = 0.025/HR = 0.14, 95% CI = 0.02–1.06, p = 0.057) a positive effect on RFS in FD patients, angiotensin-converting enzyme inhibitors (p = 0.008/HR = 10.74, 95% CI = 1.20–96.17, p = 0.034) and magnesium (p = 0.042/HR = 5.28, 95% CI = 0.88–31.59, p = 0.067) a negative impact on CSS in FD patients. In multivariate analysis, the only significant drug effects were the negative impact of angiotensin-converting enzyme inhibitors (HR = 15.20, 95% CI = 1.30–177.67, p = 0.030) and magnesium (HR = 22.87, 95% CI = 1.57–333.81), p = 0.022) on CSS in FD patients, and the positive impact of statins (HR = 0.12, 95% CI = 0.01–0.97, p = 0.047) on RFS in FD patients. Impact of non-oncologic drugs on RFS and CSS was small in this prospective study. Thus, appropriate treatment of comorbidities is encouraged.
What is known and Objective
Hepatic impairment (HI) is a known risk factor for drug safety. The MELD score (Model-for-endstage-liver-disease), calculated from serum creatinine, bilirubin and International Normalized Ratio (INR), is a promising screening tool corresponding to Child-Pugh Score (CPS) for drug adjustment. We tested the feasibility of MELD as an automatic screening tool accounting for correct calculation, interfering factors (IF) and detection of patients corresponding to CPS-B/C potentially requiring drug adjustment.
Methods
We retrospectively calculated MELD for a 3-month cohort of surgical patients and assessed need for adjustment of MELD parameters to standard values. IF for INR (oral anticoagulants) and serum creatinine (renal insufficiency (RI; eGFR<60 ml/min/1.73m²); as well as drugs elevating creatinine levels (DECL)) and the number of patients with MELD scores corresponding to CPS-B/C were analysed. For MELD ≥7.5, liver and bile diagnoses were recorded.
Results and discussion
Of 1183 patients, MELD was calculable for 761 (64%; median 7.5, range 6.4–36.8). Parameters had to be adjusted for 690 (91%) patients. IF of parameters were RI in 172 (23%), INR-elevating drugs in 105 (14%) and DECL in 33 (4%) patients. Of 335 (44%) patients with MELD ≥7.5, 122 (36%) had documented liver or bile diagnoses. MELD 10-<15 (corresponding to CPS-B) was found for 105 (14%), MELD ≥15 (corresponding to CPS-C) for 66 (9%) of the 761 patients with a calculated MELD. Referred to all patients, drug adjustments due to possible HI were recommendable for 14% of patients with suspected CPS-B/C.
What is new and Conclusion
MELD is a feasible screening tool for HI as a risk factor for drug safety at hospital admission when appropriately considering correct parameter adjustment and RI and INR-elevating drugs as IF. Further evaluation of sensitivity and specificity is needed.
Background Chronic drug therapy may impact recurrence and survival of patients with bladder cancer and thus be of concern regarding drug choice and treatment decisions. Currently, data are conflicting for some drug classes and missing for others. Objective To analyze the impact of common non-oncologic chronic drug intake on survival in patients with bladder cancer and radical cystectomy. Setting. Patients with bladder cancer and radical cystectomy (2004–2018) at the University Hospital Munich. Method Data from an established internal database with patients with bladder cancer and radical cystectomy were included in a retrospective study. Drug therapy at the time of radical cystectomy and survival data were assessed and follow-up performed 3 months after radical cystectomy and yearly until death or present. Impact on survival was analyzed for antihypertensive, antidiabetic, anti-gout, antithrombotic drugs and statins, using the Kaplan–Meier method, log-rank test and Cox-regression models. Main outcome measure Recurrence free survival, cancer specific survival and overall survival for users versus non-users of predefined drug classes. Results Medication and survival data were available in 972 patients. Median follow-up time was 22 months (IQR 7–61). In the univariate analysis, a significant negative impact among users on recurrence free survival (n = 93; p = 0.038), cancer specific survival (n = 116; p < 0.001) and overall survival (n = 116; p < 0.001) was found for calcium-channel blockers, whereas angiotensin-receptor-blockers negatively influenced overall survival (n = 96; p = 0.020), but not recurrence free survival (n = 73; p = 0.696) and cancer specific survival (n = 96; p = 0.406). No effect of angiotensin-receptor-blockers and calcium-channel blockers was seen in the multivariate analysis. None of the other studied drugs had an impact on survival. Conclusion There was no impact on bladder cancer recurrence and survival for any of the analyzed drugs. Considering our results and the controverse findings in the literature, there is currently no evidence to withhold indicated drugs or choose specific drug classes among the evaluated non-oncologic chronic drug therapies. Thus, prospective studies are required for further insight. Trail registration This is part of the trial DRKS00017080, registered 11.10.2019.
What is known and objective
Renal impairment (RI) and renal drug-related problems (rDRP) often remain unrecognized in the community setting. A “renal pharmacist consultant service” (RPCS) at hospital admission can support patient safety by detecting rDRP. However, the efficient information sharing from pharmacists to physicians is still discussed. The aim of the study was to test the implementation of a RPCS and its effectiveness on prescription changes and to evaluate two ways of written information sharing with physicians.
Methods
Urological patients with eGFRnon-indexed of 15-59 ml/min and ≥1 drug were reviewed for manifest and potential rDRP at admission by a pharmacist. Written recommendations for dose or drug adaptation were forwarded to physicians comparing two routes: July-September 2017 paper form in handwritten chart; November 2017-January 2018 digital PDF document in the electronic patient information system and e-mail alert. Prescription changes regarding manifest rDRP were evaluated and compared with a previous retrospective study without RPCS.
Results and discussion
The RPCS detected rDRP in 63 of 234 (26.9%) patients and prepared written recommendations (median 1 rDRP (1-5) per patient) concerning 110 of 538 (20.5%) drugs at admission. For manifest rDRP, acceptance rates of recommendations were 62.5% (paper) vs 42.9% (digital) (P = 0.16). Compared with the retrospective study without RPCS (prescription changes in 21/76 rDRP; 27.6%), correct prescribing concerning manifest rDRP significantly increased by 27.1%.
What is new and conclusion
A RPCS identifies patients at risk for rDRP and significantly increases appropriate prescribing by physicians. In our hospital (no electronic order entry, electronic chart or ward pharmacists), consultations in paper form seem to be superior to a digital PDF document.
Purpose
Two to seven percent of the German adult population has a renal impairment (RI) with an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2. This often remains unrecognized and adjustment of drug therapy is lacking. To determine renal function in clinical routine, the CKD-EPI equation is used to calculate an indexed eGFR (ml/min/1.73m2). For drug dosing, it has to be individualized to a non-indexed eGFR (ml/min) by the patient’s body surface area. Here, we investigated the number of patients admitted to urological wards of a teaching hospital with RI between July and December 2016. Additionally, we correctly used the eGFRnon-indexed for drug and dosage adjustments and to analyse the use of renal risk drugs (RRD) and renal drug-related problems (rDRP).
Methods
In a retrospective observational study, urological patients with pharmacist-led medication reconciliation at hospital admission and eGFRindexed (CKD-EPI) of 15–59 ml/min/1.73m2 were identified. Indexed eGFR (ml/min/1.73m2) was recalculated with body surface area to non-indexed eGFR (ml/min) for correct drug dosing. Medication at admission was reviewed for RRD and based on the eGFRnon-indexed for rDRP, e.g. inappropriate dose or contraindication.
Results
Of 1320 screened patients, 270 (20.5%) presented with an eGFRindexed of 15–59 ml/min/1.73m2. After readjustment, 203 (15.4%) patients had an eGFRnon-indexed of 15–59 ml/min. Of these, 190 (93.6%) used ≥ 1 drugs at admission with 660 of 1209 (54.7%) drugs classified as RRD. At least one rDRP was identified in 115 (60.5%) patients concerning 264 (21.8%) drugs.
Conclusion
Renal impairment is a common risk factor for medication safety in urologic patients admitted to a hospital. Considerable shifts were seen in eGFR-categories when correctly calculating eGFRnon-indexed for drug dosing purposes. The fact that more than half of the study patients showed rDRP at hospital admission underlines the need to consider this risk factor appropriately.
Background Hepatic insufficiency can affect patient safety and should therefore be considered during drug therapy. Hospital admission offers an ideal point to screen for patients at risk and to adjust drug therapy accordingly. Objective To assess the number of patients admitted to hospital with clinically elevated liver parameters. To identify high-risk patients in need of potential drug therapy adjustment to liver function by calculation of liver scores. Finally, to investigate whether pre-hospital medication needed adjustment to liver function. Setting Patients admitted to surgical wards of a tertiary teaching hospital. Method Surgical patients were included in a 3-month retrospective study. A pharmacist-led screening process, including recording of elevated liver parameters and calculation of liver scores (Child–Pugh-score, Model of End-stage Liver Disase [MELD], MELDNa), was used to assess frequency of hepatic insufficiency and patients potentially needing medication adjustment. Additionally, pre-hospital medication was checked for contraindications and correct dosage with regard to liver function. Main outcome measure Percentage of surgical patients with clinically elevated liver parameters at admission, percentage of patients with hepatic insufficiency potentially needing drug therapy adjustment, and percentage of pre-hospital drug intakes not adjusted to liver function. Results Of 1200 patients, 130 (11%) had at least one clinically relevant elevated liver parameter at hospital admission. Of these, need for drug adjustment to liver function was found for 16–36%, depending on the liver score used (equivalent to 2–4% of all patients), with the highest number of patients detected by the MELD- and MELDNa-score. Pre-hospital medication concerned 719 drug intakes and was contraindicated in 2%, dosage not adjusted in 3%, and evaluation not possible in 44% of all drug intakes due to lack of information on the drug. Conclusion A significant proportion of patients admitted for surgery have clinically elevated liver parameters and potentially need medication adjustment. A pharmacist-led screening already at hospital admission can support the identification of patients with clinically relevant elevated liver parameters and patients at risk by calculating liver scores under routine conditions. Evaluation of drug adjustment to liver function is challenging, since no data are available in routine resources for a considerable number of drugs.
Tyrosinkinaseinhibitoren beeinflussen renale Transporter: was bedeutet das für die klinische Praxis?
(2019)
Background
QTc interval prolongation can result in potentially lethal arrhythmias. One risk factor is QTc-prolonging drugs, including some antifungals often used in hemato-oncology patients. Screening tools for patients at risk have not yet been investigated in this patient population.
Aim
Our aim was to evaluate the sensitivity and specificity of five QTc risk scores in hemato-oncology patients receiving systemic antifungal therapy.
Method
Data were retrieved from an internal study database including adult hemato-oncology patients prescribed systemic antifungal therapy. Data on QTc-prolonging medication, risk factors for QTc prolongation, and electrocardiograms (ECG) were collected retrospectively for a period of 12 months. The QTc risk scores according to Tisdale, Vandael, Berger, Bindraban, and Aboujaoude as well as their sensitivity and specificity were calculated.
Results
During the evaluated period, 77 patients were prescribed systemic antifungals resulting in 187 therapy episodes. Regarding therapy episodes, median age was 56 years (IQR 44–68), 41% (77) were female, and a median of 3 QTc-prolonging drugs were prescribed (range 0–6). ECGs were available for 45 (24%) of the therapy episodes 3–11 days after initiation of the antifungal therapy, 22 of which showed QTc prolongation. Regarding these 45 therapy episodes, sensitivity and specificity of the risk scores were calculated as follows: Tisdale 86%/22%, Vandael 91%/35%, Berger 32%/83%, Bindraban 50%/78%, Aboujaoude 14%/87%.
Conclusion
The QTc risk scores according to Tisdale and Vandael showed sufficient sensitivity for risk stratification in the studied patient population. In contrast, risk scores according to Berger, Bindraban, and Aboujaoude cannot be considered suitable due to poor sensitivity.
Hepatic impairment (HI) influences the pharmacokinetics and pharmacodynamics of drugs and represents an important risk factor for drug safety. A reliable screening tool for HI identification at hospital admission by pharmacists would be desirable but is currently lacking. Therefore, we tested four liver scores as potential screening instruments. We retrospectively recorded liver/bile diagnoses, symptoms and abnormalities (summarized as hepatic findings) of 200 surgical patients followed by an assessment of the relevance of these findings for drug therapy (rating). The agreement between the Model of Endstage Liver Disease (MELD), Non-alcoholic fatty liver disease fibrosis score (NFS), Fibrosis 4 index (FIB-4), and aspartate-aminotransferase to platelet ratio index (APRI) and the rating was quantified by Cohen’s Kappa. The performance of the scores in this setting was further evaluated by their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Of 200 patients, 18 (9%) had hepatic findings relevant for drug therapy. Fair agreement was found for FIB-4 and MELD and slight agreement for APRI and NFS compared to the rating. The highest values for sensitivity, specificity, PPV, and NPV were 41.2% (MELD), 99.3% (APRI), 66.7% (APRI), and 93.6% (MELD), respectively. Due to low performance, none of the scores can be recommended for clinical use as a single screening tool for HI at hospital admission.