The Role of a Clinical Pharmacist in the Identification of Potentially Inadequate Drugs Prescribed to the Geriatric Population in Low-Resource Settings Using the Beers Criteria: A Pilot Study.

Population aging is a global phenomenon. Each country in the world faces an increased number of older persons in the total population. With aging, a high prevalence of multiple chronic diseases occurs, leading to the use of complex therapeutic regimens and often to polypharmacy. Potentially inappropriate medication (PIM) is a medicine prescribed to a patient for whom the risks outweigh the benefits. Today, several tools are used to evaluate the use of pharmacotherapy in older adults, one of them is the 2019 AGS Beers Criteria. In this prospective, pilot study, we aimed to investigate if the number of PIMs in elderly patients would be significantly reduced if a clinical pharmacist performed a pharmacotherapy review. The study included 66 patients over 65 years of age who were hospitalized at the 1200-bed university hospital. The intervention was conducted by a clinical pharmacist who reviewed the patients' pharmacotherapy and provided written suggestions to physicians. The pharmacotherapy was again reviewed at the patients' discharge from the hospital. A total number of 204 PIMs were identified in the pharmacotherapy of the study population. At discharge, the number of PIMs decreased to 67. A total of 67% of the pharmacist's suggestions were accepted by the physicians. The pharmacist's intervention led to significant decrease in the number of PIMs on patients' discharge letters.

Understanding hemoglobin contribution to high-dose methotrexate disposition-population pharmacokinetics in pediatric patients with hematological malignancies.

PURPOSE: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) and to describe the influence of variability factors. METHODS: The study included 50 patients of both sexes (aged 1-18 years) who received 3 or 5 g/m2 of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis. Parameter estimation was performed by first-order conditional estimation method with interaction (FOCEI), whereas stepwise covariate modeling was used to assess variability factors. RESULTS: The final model is a two-compartment model that incorporates the effect of body surface area and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical subject were estimated at 5.75 L/h/m2 for clearance (CL), 21.3 L/m2 for volume of the central compartment (V1), 8.2 L/m2 for volume of the peripheral compartment (V2), and 0.087 L/h/m2 for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 32% in MTX CL was observed among patients' hemoglobin values reported in the study. CONCLUSION: The developed population pharmacokinetic model can contribute to the therapy optimization during HDMTX in pediatric patients with ALL and NHL. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to the disposition of HDMTX.

Association of clozapine and norclozapine levels with patient and therapy characteristics-focus on interaction with valproic acid.

PURPOSE: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. METHODS: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients' data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. RESULTS: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. CONCLUSION: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.

Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes.

Clinical pharmacy as an area of practice, education and research started developing around the 1960s when pharmacists across the globe gradually identified the need to focus more on ensuring the appropriate use of medicines to improve patient outcomes rather than being engaged in manufacturing and supply. Since that time numerous studies have shown the positive impact of clinical pharmacy services (CPS). The need for wider adoption of CPS worldwide becomes urgent, as the global population ages, and the prevalence of polypharmacy as well as shortage of healthcare professionals is rising. At the same time, there is great pressure to provide both high-quality and cost-effective health services. All these challenges urgently require the adoption of a new paradigm of healthcare system architecture. One of the most appropriate answers to these challenges is to increase the utilization of the potential of highly educated and skilled professionals widely available in these countries, i.e., pharmacists, who are well positioned to prevent and manage drug-related problems together with ensuring safe and effective use of medications with further care relating to medication adherence. Unfortunately, CPS are still underdeveloped and underutilized in some parts of Europe, namely, in most of the Central and Eastern European (CEE) countries. This paper reviews current situation of CPS development in CEE countries and the prospects for the future of CPS in that region.

Methotrexate concentrations and associated variability factors in high dose therapy of children with acute lymphoblastic leukemia and non-Hodgkin lymphoma.

Monitoring and optimization procedures improved high dose methotrexate (HDMTX) treatment outcomes. However, there are still some concerns regarding unexplained concentration variability. The objective of this study was to evaluate drug concentrations and associated variability factors in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) on HDMTX. Fifty patients (aged 1-18 years), receiving in total 184 HDMTX cycles of 3 or 5 g/m2/24 h infusion, were included in the study. Comparisons of MTX concentrations and concentrations to dose ratio between two dosing groups were conducted by Mann-Whitney U test. Regression analysis was performed with transformed data to assess relationship between MTX concentration to dose ratio and patient characteristics, biochemical analysis and therapy data. Statistically significant difference in concentrations between 3 and 5 g/m2 dosing groups was detected only at 24 h after the start of infusion (p < 0.001), but not at 48 and 72 h (p > 0.05). There was no difference between dose-normalized concentrations. Regression analysis showed that 73.9% of variability in dependent variable can be explained by included variables: time since dose, creatinine clearance (CrCl), hemoglobin and certain concomitant therapy. Our results highlight the importance of not only renal function and concomitant therapy, but also hemoglobin in reducing the variation in MTX concentrations. Therefore, monitoring of aforementioned biochemical parameters during HDMTX is important not only to assess toxicity, but also in predicting their impact on drug level.

Lidocaine clearance as pharmacokinetic parameter of metabolic hepatic activity in patients with impaired liver.

Background: The study aimed to estimate lidocaine (LID) pharmacokinetic parameter values in patients with impaired liver function, level of correlation between the pharmacokinetic parameters and Child-Pugh class and change in pharmacokinetic parameters after liver tumor resection compared to the preoperative value. Methods: Patients with impaired liver function were subject to the LID test 1 day prior to, 3 and 7 days after the intervention. LID was administered in single i.v. dose of 1 mg/kg. Blood samples were collected at 15, 30 and 90 minutes after drug administration. Non-compartmental analysis was applied for calculating the pharmacokinetic parameters. Results: The study included 17 patients with the diagnosis of cirrhosis and 41 patients with liver tumor. In both groups of patients, the values of the coefficients of correlation show the best correlation between clearance (CL) and Child-Pugh score (-0.693, p<0.005) over other pharmacokinetic parameters. The results indicate worsening hepatic function on 3rd day after operation in comparison to the values of LID CL prior to operation (mean LID CL for patients with Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively; while for B class are 16.89 L/h, 22.65 L/h, respectively). On day 7th, the values of LID CL (mean value for patients with Child-Pugh class A and B are 40.98 L/h and 21.46 L/h, respectively) are increased in comparison to 3rd day after. Conclusions: LID pharmacokinetic parameters consequently changed according to the severity of liver impairment, assessed by Child-Pugh score. Values of LID CL and volume of distribution (Vd) coupled with standard biochemical parameters may be used for preoperative assessment of liver function and monitoring of its postoperative recovery.

Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology.

OBJECTIVE: Therapeutic monoclonal antibodies in oncology are slowly becoming the dominant treatment option for many different cancer types. The main route of administration, infusion, requires extensive product preparations, patient hospitalization and close monitoring. Patient comfort improvement, staff workload reduction and cost savings dictated the development of subcutaneous formulations. The aim of this review is to present pharmacokinetic characteristics of subcutaneous products, discuss the differences between intravenous and subcutaneous routes and to point out the advantages as well as challenges of administration route shift from the formulation development and pharmacometric angle. DATA SOURCES: Food and Drug administration's Purple book database and electronic medicines compendium were used to identify monoclonal antibodies in oncology approved as subcutaneous forms. Using keywords subcutaneous, monoclonal antibodies, pharmacokinetics, model, as well as specific drugs previously identified, both PubMed and ScienceDirect databases were researched. DATA SUMMARY: There are currently six approved subcutaneous onco-monoclonal antibodies on the market. For each of them, exposure to the drug was similar in relation to infusion, treatment effectiveness was the same, administration was well tolerated by the patients and costs of the medical service were reduced. CONCLUSION: Development of subcutaneous forms for existing and emerging new monoclonal antibodies for cancer treatment as well as shifting from administration via infusion should be encouraged due to patient preference, lower costs and overall lack of substantial differences in efficacy and safety between the two routes.

Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria

Abstract The study aimed to estimate and compare the prevalence and type of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) between the STOPP/START original (v1) and updated version (v2) among older patients in various settings, as well as associated factors. The study included 440 patients attending a community pharmacy, 200 outpatients and 140 nursing home users. An increase in the prevalence of STOPP v2 (57.9%) compared to v1 (56.2%) was not statistically significant in the total sample and within each setting (p>0.05). A decrease in the prevalence of START v1 (55.8%) to v2 (41.2%) was statistically significant (p<0.001) in the total sample and within each setting (p<0.05). Drug indication (32.9%) and fall-risk medications (32.2%) were most commonly identified for STOPP v2, while cardiovascular system criteria (30.5%) were the most frequently detected for START v2. The number of medications was the strongest predictor for both STOPP v1 and v2, with odds ratio values of 1.35 and 1.34, respectively. Patients' characteristics associated with the occurrence of STOPP and START criteria were identified. According to both STOPP/START versions, the results indicate a substantial rate of potentially inappropriate prescribing among elderly patients. The prevalence of PIMs was slightly higher with the updated version, while the prevalence of PPOs was significantly lower

Review of the Clinical Pharmacokinetics, Efficacy and Safety of Pembrolizumab.

BACKGROUND: Treatment of various types of cancer has been improved significantly with the discovery of biological drugs that act as immune checkpoint inhibitors (ICIs). Pembrolizumab is a humanized monoclonal anti- PD-1 antibody currently approved for the treatment of a wide range of tumors, with more indications still being investigated in ongoing clinical trials. OBJECTIVE: The aim of this paper is to present all currently available data regarding pembrolizumab pharmacokinetic and pharmacodynamic characteristics. Also, the possibility of using predictive biomarkers to monitor patients during cancer treatment is discussed. METHODS: Database research was carried out (PubMed, ScienceDirect). Information was gathered from original articles, the European Medicines Agency datasheets and results from clinical trials. RESULTS: This review summarizes present-day knowledge about the pharmacokinetics, different modeling approaches and dosage regimens, efficacy and safety of pembrolizumab and therapeutic monitoring of disease progression. CONCLUSION: This review points out consistent pharmacokinetic characteristics of pembrolizumab in various cancer patients, the lack of pharmacokinetic-pharmacodynamic/outcome relationships, and the need for adequate biomarkers to predict treatment success. Hence, there is a clear necessity for more data and experience in order to optimize pembrolizumab treatment for each individual patient.

Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study.

BACKGROUND: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia. METHODS: A prospective cohort study was conducted including adult patients diagnosed with an initial episode of HA CDI. Their demographic and clinical characteristics associated with risk factors for CDI were documented. Outcomes such as all-cause 30-day mortality, cure of infection, diarrhoea relaps and recurrence of disease were followed. Patients were assigned to cancer and non-cancer groups. Within the cancer group, patients were divided into the solid tumour subgroup and haematological malignancy subgroup. RESULTS: During a 7-year period, HA CDI was observed in 28 (5.1%) patients with haematological malignancy, 101 (18.3%) patients with solid tumours and 424 (76.7%) non-cancer patients. Older age (OR 1.04, 95% CI 1.02 to 1.07, p<0.001), admission to the intensive care unit (ICU) (OR 2.61, 95% CI 1.37 to 4.95, p=0.003), mechanical ventilation (OR 5.19, 95% CI 2.78 to 9.71, p<0.001) and use of antibiotics prior to CDI (OR 1.04, 95% CI 1.02 to 1.06, p=0.02) were associated with increased mortality. Compared with patients with solid tumours, patients with haematological malignancy were younger (65 vs 57 years, p=0.015), did not require ICU admission (25.0% vs 0%) or mechanical ventilation (8.9% vs 0%) and were treated longer with antibiotics prior to CDI (14 vs 24 days, p=0.002). CONCLUSIONS: Patients with haematological malignancy were exposed to different risk factors for CDI associated with mortality compared with patients with solid tumours and non-cancer patients. Older age, ICU stay and mechanical ventilation, but not presence or type of cancer, predicted the all-cause 30-day mortality.

Population exposure-response model of 131I in patients with benign thyroid disease.

PURPOSE: The study aimed to explore the relationship of different exposure measures with 131I therapy response in patients with benign thyroid disease, estimate the variability in the response, investigate possible covariates, and discuss dosing implications of the results. METHODS: A population exposure-response analysis was performed using nonlinear mixed-effects modelling. Data from 95 adult patients with benign thyroid disease were analysed. Evaluated exposure parameters were: administered radioactivity dose (Aa) [MBq], total absorbed dose (ABD) [Gy], maximum of absorbed dose-rate (MXR) [Gy/h] and biologically effective dose (BED) [Gy]. The response was modelled as ordered categorical data: hyper-, eu- and hypothyroidism. The final model performance was evaluated by a visual predictive check. RESULTS: The probability of the outcome following 131I therapy was best described by a proportional-odds model, including the log-linear model of 131I effect and the exponential model of the response-time relationship. All exposure measures were statistically significant with p<0.001, with BED and ABD being statistically better than the other two. Nevertheless, as BED resulted in the lowest AIC value, it was included in the final model. Accordingly, BED value of 289.7 Gy is associated with 80% probability of successful treatment outcome 12 months after 131I application in patients with median thyroid volume (32.28 mL). The target thyroid volume was a statistically significant covariate. The visual predictive check of the final model showed good model performance. CONCLUSION: Our results imply that BED formalism could aid in therapy individualisation. The larger thyroid volume is associated with a lower probability of a successful outcome.

Impact of pharmacist's intervention on decreasing erlotinib interactions in the treatment of lung cancer patients in low resource settings.

BACKGROUND: This study aimed to demonstrate that having clinical pharmacist as a member of oncology team in low and middle income countries might lead to significant reduction in the number of erlotinib interactions in the treatment of non-small cell lung cancer patients. METHODS: A group of 44 patients was labeled as intervention group and they were analyzed prospectively in the period from 1 January 2017 to 1 May 2018 during clinical pharmacist's participation in regular weekly multidisciplinary oncology team meetings. The control group consisted of 44 out of 110 patients treated with erlotinib before the involvement of a clinical pharmacist in oncology team, match paired with 44 patients in intervention group. RESULTS: Clinically significant interactions were identified in two-thirds of studied patients (57 out of 88). Most drug interactions, 38%, potentially result in decrease of serum concentration of erlotinib. Clinical pharmacist provided therapy modification suggestions for 32 out of 44 (72.72%) patients in the intervention group, most of which were accepted by doctors. In the intervention group, there were significantly less clinically significant interactions compared to the control group (10 versus 24, p = 0.002). Progression-free survival was significantly longer in the pharmacist's intervention group (p = 0.001). CONCLUSIONS: Clinical pharmacist's intervention led to significant decrease in erlotinib interactions which may result in treatment optimization of lung cancer patients.

Pentoxifylline with metformin treatment improves biochemical parameters in patients with nonalcoholic steatohepatitis.

BACKGROUND: The progression of the nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) is multifactorial, and there is still a lack of approved medications for its treatment. The study aimed to evaluate the impact of combined treatment with Pentoxifylline and Metformin on biochemical parameters in patients with Nash. Setting: Outpatient hepatology clinic. METHODS: A prospective trial was conducted. The first cohort included patients with biopsy-proven Nash, while the second cohort consisted of patients with biopsy-confirmed NAFLD. Blood tests were checked at baseline and every three months. Pentoxifylline at a dosage of 400 mg t.i.d. and Metformin at the dosage of 500 mg t.i.d. were introduced for six months in Nash group. The impact of the treatment was assessed based on biochemical results after combined treatment with low-cost medications. RESULTS: All 33 Nash patients completed 24 weeks of treatment. We observed significant improvement (p<0.05) of median values after treatment for the following parameters: serum uric acid levels decreased by 51.0 mmol/L, calcium decreased for 0.27 mmoL/L, magnesium showed an increase of 0.11 mmoL/L. Insulin resistance improved as a reduction of HOMA - IR by 1.3 was detected. A significant decrease of median in liver enzymes, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase by 24.0 U/L, 9.1 U/L, 10.8 U/L respectively, was noted. CONCLUSIONS: Pentoxifylline and Metformin may provide possible treatment option in Nash. Some new potential benefit of the therapy in improving liver function whilst decreasing cardiovascular risk was perceived.

Understanding variability in the pharmacokinetics of atypical antipsychotics - focus on clozapine, olanzapine and aripiprazole population models.

Antipsychotic medicines are widely used for the management of psychotic symptoms regardless of the underlying diagnosis. Most atypical antipsychotics undergo extensive metabolism prior to excretion. Various factors may influence their pharmacokinetics, particularly elimination, leading to highly variable drug concentrations between individual patients following the same dosing regimen. Population pharmacokinetic approach, based on nonlinear mixed effects modeling, is a useful tool to identify covariates explaining pharmacokinetic variability, as well as to characterize and distinguish unexplained residual and between-subject (interindividual) variability. In addition, this approach allows the use of both sparsely and intensively sampled data. In this paper, we reviewed the pharmacokinetic characteristics of clozapine, olanzapine and aripiprazole, focusing on a population modeling approach. In particular, models based on a nonlinear mixed effects approach performed by NONMEM® software in order to identify and quantify sources of pharmacokinetic variability are presented. Population models were identified through systematic searches of PubMed and sixteen studies were selected. Some of the factors identified that significantly contribute to variability in elimination among clozapine, olanzapine, and aripiprazole are demographic characteristics, body weight, genetic polymorphism, smoking and in some cases drug interactions. Scientific research based on pharmacometric modeling is useful to further characterize sources of variability and their combined effect.

A Simple Index for Nonalcoholic Steatohepatitis-HUFA-Based on Routinely Performed Blood Tests.

Background and objectives: Data suggests that nearly 30% of the general population have steatosis and up to 5% of this population develops nonalcoholic steatohepatitis (NASH). Liver biopsy is still considered to be the gold standard for the diagnosis of NASH. Great effort is being made toward the identification of sensitive diagnostic tests that do not involve invasive procedures to address a common concern in patients with the nonalcoholic fatty liver disease-whether they have NASH or simple steatosis. We aimed to investigate the independent predictors and develop a non-invasive, easy-to-perform, low-cost set of parameters that may be used in clinical practice to differentiate simple steatosis from NASH. Methods: А cross-sectional study of nonalcoholic fatty liver disease (NAFLD) patients divided into two groups: group I-simple steatosis (SS) and group II-biopsy-proven NASH. Strict inclusion criteria and stepwise analysis allowed the evaluation of a vast number of measured/estimated parameters. Results: One hundred and eleven patients were included-82 with simple steatosis and 29 with biopsy-proven NASH. The probability of NASH was the highest when homeostatic model assessment of insulin resistance (HOMA-IR) was above 2.5, uric acid above 380 µmol/L, ferritin above 100 µg/L and ALT above 45 U/L. An acronym of using first letters was created and named the HUFA index. This combined model resulted in an area under the receiver operator characteristic curve (AUROC) of 0.94, provided sensitivity, specificity, positive predictive value and a negative predictive value for NASH of 70.3%, 95.1%, 83.1% and 90.0%, respectively. Conclusion: We suggest a simple non-invasive predictive index HUFA that encompasses four easily available parameters (HOMA-IR, uric acid, ferritin and ALT) to identify patients with NASH, which may reduce the need for a liver biopsy on a routine basis in patients with NAFLD.

Investigation of factors influencing radioiodine (131I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach.

PURPOSE: Radioiodine (131I) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize 131I biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal 131I kinetics by developing a population model. METHODS: Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of 131I biokinetics representing the blood compartment and thyroid gland was used as the structural model. RESULTS: Results of the study indicate that the rate constant of the uptake of 131I into the thyroid (ktu) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT4), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of 131I is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for ktu from 91 (3.9) to 53.9 (4.5)%. CONCLUSIONS: This is the first population model that accounts for the influence of fT4 and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to 131I and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.

Elderly polypharmacy patients' needs and concerns regarding medication assessed using the structured patient-pharmacist consultation model.

OBJECTIVE: To evaluate elderly polypharmacy patients' needs and concerns regarding medication through the Structured Patient-Pharmacist Consultation (SPPC). METHODS: Older patients on chronic treatment with ≥5 medications were asked to fill in the SPPC form at home. A consultation with the community pharmacist, structured according to patient's answers, followed within 2-4 weeks. Logistic regression associated patients' individual treatment with care issues and consultation outcomes. RESULTS: Out of 440 patients, 39.5% experienced problems, and 46.1% had concerns about medication use. 122 patients reported reasons for discontinuing treatment. The main outcome of the consultation was a better understanding of medication use (75.5%). Side effects and/or non-adherence were identified in 50% of patients, and 26.6% were referred to the doctor. Atrial fibrillation, COPD, anticoagulants, benzodiazepines, and beta agonists/corticosteroids were associated with problems during medication use. Patients with diabetes improved their understanding of medication use significantly. CONCLUSION: Patients on benzodiazepines, anticoagulants, and beta agonists/corticosteroids, with atrial fibrillation and/or COPD, may have a higher potential for non-adherence. Counseling patients based on the SPPC model may be particularly useful for patients with diabetes. PRACTICE IMPLICATIONS: The SPPC model is a useful tool for counseling based on patient needs.

Evaluation of drug-related problems in older polypharmacy primary care patients.

AIMS AND OBJECTIVES: Targeting older patients with predictive factors for drug-related problems (DRPs) could make clinical medication reviews more cost-effective. The aim of this study was to identify the number, type, and potential predictive factors for DRPs in older polypharmacy patients. METHODS: Community pharmacists performed clinical medication reviews and documented DRPs, types of interventions, and their implementation in older patients. RESULTS: Three hundred eighty-eight medication reviews were analyzed, 964 DRPs (average 2.5 ± 1.9), and 1022 interventions (average 2.6 ± 2.0) were identified. The overall implementation rate of interventions was 70.1%, the highest was observed in interventions aiming to resolve the lack of therapy monitoring (86.8%). Patients with ≥12 medications had an increased risk of ≥5 DRPs (P < .001). Asthma was associated with lack of adherence (P = .002), lack of aspirin, statins, and proton pump inhibitors use with additional therapy needed (P = .002-.004). Predictive factors for drug interactions were antihypertensive medications and/or medications with narrow therapeutic index (P < .05). Lack of efficacy was associated with diabetes (P = .006). Nonsteroidal anti-inflammatory drugs were risk factors for inappropriate drug selection (P = .002). Lack of monitoring was associated with hypertension (P = .013), whereas benzodiazepines (P < .001) and aspirin (P = .021) were overused. CONCLUSION: Patients with asthma, hypertension, and diabetes and lack of statin, antithrombotic agent, and/or proton pump inhibitor use were associated with higher risks for DRPs.

Low fresh gas flow balanced anesthesia versus target controlled intravenous infusion anesthesia in laparoscopic cholecystectomy: a cost-minimization analysis.

BACKGROUND: Laparoscopic surgery is widely recognized as a well-tolerated and effective method for cholecystectomy. It is also considered cost saving because it has been associated with a decreased hospital length of stay. Variables that might lead to increased costs in laparoscopic surgery are the technique and drugs used in anesthesia. OBJECTIVE: The goal of this study was to compare the costs of 2 anesthetic techniques used in laparoscopic cholecystectomy (LC)--balanced versus IV anesthesia--from the standpoint of an outpatient surgical department, with a time horizon of 1 year. METHODS: Patients scheduled to undergo elective LC were enrolled in this prospective case study. Patients were randomly allocated to receive balanced anesthesia, administered as low fresh gas flow (LFGF) with inhalational sevoflurane and IV sufentanil in a target controlled infusion (LFGF SS group), or IV anesthesia, administered as IV propofol/sufentanil in a target controlled infusion (TCI group). We used a microcosting procedure to measure health care resource utilization in individual patients to detect treatment differences. The costs of medications used for the induction and maintenance of anesthesia during surgery were considered for LFGF SS and TCI. Other end points included duration of anesthesia; mean times to early emergence, tracheal extubation, orientation, and postanesthesia discharge (PAD); pain intensity before first analgesia; number of analgesics required in the first 24 hours after surgery; and prevalences of nausea, vomiting, and agitation. RESULTS: A total of 60 patients were included in this analysis (male/female ratios in the LFGF SS and TCI groups: 11/19 and 12/18, respectively; mean [SD] ages, 48 [7.9] and 47 [8.6] years; and mean [SD] body mass indexes, 26 [2.0] and 26 [3.0] kg/m2). The costs of anesthetics were significantly lower with LFGF SS compared with TCI (euro17.40 [euro2.66] vs euro22.01 [euro2.50] [2006 euros]). Times to early emergence and tracheal extubation were significantly shorter with LFGF SS than TCI (5.97 [1.16] vs 7.73 [1.48] minutes and 7.57 [1.07] vs 8.87 [1.45] minutes, respectively). There were no significant between-group differences in mean duration of anesthesia; times to orientation and PAD; pain intensity before first analgesia; number of analgesics required in the first 24 hours; or prevalences of nausea, vomiting, and agitation. Because no clinically significant differences in the anesthetic results were observed, a cost-minimization analysis was conducted and found that using LFGF SS, the outpatient surgical department could realize a budget savings of euro454 per 100 patients. For the nearly 1000 expected patients per year, the savings for the department was calculated as euro4540. CONCLUSION: The results from this cost analysis in these patients who underwent elective LC suggest that the use of sevoflurane through the LFGF technique would be cost saving in this outpatient surgical department.

Population pharmacokinetic model of carbamazepine derived from routine therapeutic drug monitoring data.

The aim of the present study was to develop a population pharmacokinetic model of carbamazepine from routine therapeutic drug monitoring data. Steady-state carbamazepine plasma concentrations determined by homogenous enzyme immunoassay technique, dosing history including cotherapy, schedule of blood sampling, and patients' demographic characteristics were collected retrospectively from patients' chart histories. A one-compartment model was fitted to the data using nonlinear mixed effects modeling. The influence of weight, age, gender, smoking, allergy, carbamazepine daily dose, and cotherapy on clearance (CL/F) was evaluated. Additionally, bioavailability of controlled-release relative to immediate-release tablets was assessed. Two hundred sixty-five patients (423 concentrations) were used to develop a population pharmacokinetic model. The population estimate of CL/F from the base model was 5.14 L/h with interindividual variability of 50.20%. Patients' gender, age, smoking, allergy, cotherapy with lamotrigine and benzodiazepines had no effect on CL/F. Patient weight (WT), daily carbamazepine dose (DCBZ), daily dose of phenobarbitone (DPB) and valproic acid (VPA), when its daily dose exceeded 750 mg, significantly influenced CL/F and were included in the final model:[equation: see text] where VPA is 1 if dose is greater than 750 mg or 0 otherwise. No difference in bioavailability of carbamazepine between controlled- and immediate-release tablets was detected. The model predictions in the validation set had no bias and satisfactory precision. The model can be used for estimation of carbamazepine CL/F in individual patients in the postautoinduction phase and for selection of optimum dosing regimen in routine patient care.