Deprescribing: An umbrella review.

This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic outcomes, barriers and facilitators, and tools for deprescribing are presented. The Medline database was used. The search was limited to systematic reviews and meta-analyses published in English up to April 2022. Reviews reporting deprescribing were included, while those where depre-scribing was not planned and supervised by a healthcare professional were excluded. A total of 94 systematic reviews (23 meta--analyses) were included. Most explored clinical or humanistic outcomes (70/94, 74 %); less explored attitudes, facilitators, or barriers to deprescribing (17/94, 18 %); few focused on tools (8/94, 8.5 %). Reviews assessing clinical or humanistic outcomes were divided into two groups: reviews with deprescribing intervention trials (39/70, 56 %; 16 reviewing specific deprescribing interventions and 23 broad medication optimisation interventions), and reviews with medication cessation trials (31/70, 44 %). Deprescribing was feasible and resulted in a reduction of inappropriate medications in reviews with deprescribing intervention trials. Complex broad medication optimisation interventions were shown to reduce hospitalisation, falls, and mortality rates. In reviews of medication cessation trials, a higher frequency of adverse drug withdrawal events underscores the importance of prioritizing patient safety and exercising caution when stopping medicines, particularly in patients with clear and appropriate indications.

Effectiveness of pharmacist-led medication reconciliation on medication errors at hospital discharge and healthcare utilization in the next 30 days: a pragmatic clinical trial.

Transitions of care often lead to medication errors and unnecessary healthcare utilization. Medication reconciliation has been repeatedly shown to reduce this risk. However, the great majority of evidence is limited to the provision of medication reconciliation within clinical trials and countries with well-established clinical pharmacy. Thus, this pragmatic, prospective, controlled trial evaluated the effectiveness of routine pharmacist-led medication reconciliation compared to standard care on medication errors and unplanned healthcare utilization in adult general medical patients hospitalized in a teaching hospital in Slovenia. All patients hospitalized in a ward where medication reconciliation was integrated into routine clinical practice were included in the intervention group and received admission and discharge medication reconciliation, coupled with patient counselling. The control group consisted of randomly selected patients from the remaining medical wards. The primary study outcome was unplanned healthcare utilization within 30 days of discharge, and the secondary outcomes were clinically important medication errors at hospital discharge and serious unplanned healthcare utilization within 30 days of discharge. Overall, 414 patients (53.4% male, median 71 years) were included-225 in the intervention group and 189 in the control group. In the intervention group, the number of patients with clinically important medication errors at discharge was significantly lower (intervention vs control group: 9.3% vs 61.9%). Multiple logistic regression revealed that medication reconciliation reduced the likelihood of a clinically important medication error by 20-fold, while a higher number of medications on admission was associated with an increased likelihood. However, no significant differences were noted in any and serious unplanned healthcare utilization (intervention vs control group: 33.9% vs 27.8% and 20.3% vs 14.6%, respectively). The likelihood of serious healthcare utilization increased with the age of the patient, the number of medications on admission and being hospitalized for an acute medical condition. Our pragmatic trial confirmed that medication reconciliation, even when performed as part of routine clinical practice, led to a substantial reduction in the risk of clinically important medication errors at hospital discharge but not to a reduction in healthcare utilization. Medication reconciliation is a fundamental, albeit not sufficient, element to ensure patient safety after hospital discharge. Clinical Trial Registration: https://clinicaltrials.gov/search?id=NCT06207500, identifier NCT06207500.

Real-world outcomes of immunotherapy with or without chemotherapy in first-line treatment of advanced non-small cell lung cancer.

Background: Immunotherapy alone (mono-IT) or combined with chemotherapy (chemo-IT) has recently become the cornerstone of first-line treatment for advanced non-small cell lung cancer (NSCLC) patients. Here, real-world outcomes of first-line mono-IT and chemo-IT of advanced NSCLC treated within routine clinical practice at a single academic center in the Central Eastern European (CEE) region are presented. Materials and methods: A total of 176 consecutive patients with advanced NSCLC treated with mono-IT (118 patients) or chemo-IT (58 patients) were included. At the participating institution, all medical data relevant for providing oncology care are collected prospectively and in a standardized manner using purposely created pro-forms. Adverse events (AEs) were recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE). The Kaplan-Meier method was used to estimate median overall survival (mOS) and median duration of treatment (mDOT). Results: The 118 patients in the mono-IT cohort had a median age of 64 years, most were male (59%), 20% had ECOG PS ≥2, and 14% had controlled CNS metastases at baseline. With a median follow-up time (mFU) of 24.1 months, the mOS was 19.4 months (95% CI, 11.1-27.6), and the mDOT was 5.0 months (95% CI, 3.5-6.5). The 1-year OS was 62%. The 58 patients in the chemo-IT cohort had a median age of 64 years, most were male (64%), 9% had ECOG PS ≥2, and 7% had controlled CNS metastases at baseline. With a mFU of 15.5 months, the mOS was 21.3 months (95% CI, 15.9-26.7), and the mDOT was 12.0 months (95% CI, 8.3-15.6). The 1-year OS was 75%. Adverse events of severe grade were recorded in 18% and 26% of patients, and immunotherapy discontinuation due to AEs occurred in 19% and 9% in the mono-IT and chemo-IT groups, respectively. No treatment-related deaths were recorded. Conclusion: The results from the present real-world observational study from a CEE country suggest similar effectiveness and safety of first-line mono-IT and chemo-IT in patients with advanced NSCLC to those observed in randomized clinical trials. However, continuous follow-up will offer better insight into the magnitude of long-term benefits in routine clinical practice.

Deprescribing proton pump inhibitors: A study in hospitalized patients in Slovenia.

OBJECTIVE: To evaluate the possibility of deprescribing proton pump inhibitors in adult inpatients hospitalized in a teaching hospital in Slovenia. MATERIALS AND METHODS: We conducted a prospective observational clinical study in 120 patients taking a proton pump inhibitor. Data were obtained from hospital medical records and patient interviews. First, treatment compliance with relevant guidelines was assessed, and then the possibility of deprescribing was considered. RESULTS: Treatment with a proton pump inhibitor was in accordance with guidelines in only 39% of the 120 patients. In 24% of patients, the indication for proton pump inhibitor use was invalid, and 22% and 15% of patients were taking a proton pump inhibitor at a higher dose or for a longer period than recommended, respectively. Deprescribing could be undertaken in 61% of patients, as discontinuation in 38%, and dose reduction in 23%. A deprescribing possibility was noted more frequently in patients prescribed proton pump inhibitors for peptic ulcer disease, Helicobacter pylori infection, or without a valid indication (p < 0.001), as well as in patients taking a double or higher dose of a proton pump inhibitor (p < 0.001). CONCLUSION: Deprescribing of proton pump inhibitors could be undertaken in nearly 2/3 of our cohort of adult hospitalized patients. Hospitalization may serve as an opportunity to deprescribe proton pump inhibitors.

Population pharmacokinetics of cisplatin in small cell lung cancer patients guided with informative priors.

PURPOSE: Cisplatin-etoposide treatment is recommended as a first line in small cell lung cancer patients (SCLC). However, the prognosis is poor and the dosing is not tailored beyond the body surface area, which is related with indeterminate cisplatin exposure-response relationship. We aimed to evaluate cisplatin pharmacokinetics (PK) and the exposure to unbound cisplatin in SCLC patients using the informative priors, and assess the relationship between the cisplatin exposure and probability of neutropenia. METHODS: Observational clinical study was performed including 17 cisplatin-treated SCLC patients. External population cisplatin PK models were identified and NONMEM® software and $PRIOR subroutine were used for the model evaluation. The bias and precision of the model-predicted cisplatin concentrations were evaluated. The best models were combined in a final model including several sets of informative priors, which was used to estimate individual cisplatin exposure, analyze the relationship between the exposure and neutropenia and simulate several cisplatin dosing regimens in a virtual patient cohort. RESULTS: The models by Urien with the informative priors best fitted the data. The individual cisplatin exposure ranged between 2430 and 4560 µg*h/L. There was a trend of increasing probability of neutropenia and febrile neutropenia with increasing cisplatin exposure. Approximately 50%, 75% and 90% of patients receiving 60 mg/m2, 70 mg/m2 and 80 mg/m2, respectively, achieved the previously identified exposure threshold of 2860 µg*h/L. CONCLUSION: We developed a tool to individualize cisplatin dosing based on the estimated probability of neutropenia. The benefit of more intense dosing regimens in SCLC patients should be further assessed.

Adverse drug events during transitions of care : Randomized clinical trial of medication reconciliation at hospital admission.

BACKGROUND: During transitions of care, patient's medications are prone to medication errors. This study evaluated the impact of pharmacist-led medication reconciliation at hospital admission on unintentional medication discrepancies and adverse drug events. METHODS: A randomized controlled clinical trial was conducted in 120 adult medical patients hospitalized in a tertiary hospital in Slovenia. In the intervention group, a pharmacist-led medication reconciliation was performed on admission, while the control group received usual care. Patient's drug treatment before admission was compared with their admission and inpatient treatment to identify discrepancies. The intention of discrepancies and related adverse drug events were assessed as a consensus of an expert panel. RESULTS: Included patients were elderly (median 72 years) and treated with polypharmacy (median 7 medications). Upon admission, discrepancies and unintentional discrepancies, representing a medication error, were identified in 61.2% (825/1347) and 18.3% (247/1347) of medications, respectively. In the intervention group, only 29.1% (37/127) of unintentional discrepancies were reported to the physicians in person. The majority of admission discrepancies (88%) persisted through hospitalization. Unintentional discrepancies resulted in 51 adverse drug events even during hospitalization. There were no differences between the intervention and control group in the occurrence of unintentional discrepancies (p = 0.481) or adverse drug events (p = 0.801). CONCLUSIONS: Medication reconciliation at hospital admission failed to reduce unintentional discrepancies and adverse drug events, possibly due to its poor integration into clinical practice. Discrepancies resulted in patient harm even during the short period of hospitalization, which warrants the implementation of medication reconciliation at hospital admission.

Immunotherapy for Metastatic Non-Small Cell Lung Cancer: Real-World Data from an Academic Central and Eastern European Center.

BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICIs) recently became the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). Here, we present the first results of a real-world observational study on the effectiveness of ICI monotherapy in patients with advanced NSCLC treated at a single academic center in a Central and Eastern European (CEE) country. MATERIALS AND METHODS: Overall, 66 consecutive patients with advanced NSCLC treated with ICIs in everyday clinical practice, either with first-line pembrolizumab (26 patients) or second-line atezolizumab, nivolumab, or pembrolizumab (40 patients), from August 2015 to November 2018, were included. All data were retrieved from a hospital lung cancer registry, in which the data is collected prospectively. RESULTS: Included patients had a median age of 64 years, most were male (55%), 6% were in performance status ≥2, and 18% had controlled central nervous system metastases at baseline. In first-line, the median progression-free survival (mPFS) was 9.3 months, while the median overall survival (mOS) was not reached. The 1-year overall survival (OS) was 62%. In second-line, the mPFS and mOS were 3.5 months and 9.9 months, respectively, with a 1-year OS of 35%. In the overall population, adverse events of any grade were recorded in 79% of patients and of severe grade (3-4) in 12% of patients. CONCLUSION: The first real-world outcomes of NSCLC immunotherapy from a CEE country suggest comparable effectiveness to those observed in clinical trials and other real-world series, mainly coming from North America and Western European countries. Further data to inform on the real-world effectiveness of immunotherapy worldwide are needed. IMPLICATIONS FOR PRACTICE: Immunotherapy is a standard treatment of advanced non-small cell lung cancer (NSCLC). The real-world data on immunotherapy are still limited. This article presents the first data on the effectiveness of mono-immunotherapy with immune checkpoint inhibitors for patients with advanced NSCLC treated at a single academic center in a Central and Eastern European country. The survival rates and toxicity are comparable to those achieved in randomized clinical trials and other real-world series, coming mainly from North American and Western European countries. There is a pressing need to gather further data on the effectiveness of immunotherapy in everyday practice worldwide.

Time to access to novel anticancer drugs and the correlation with ESMO-Magnitude of Clinical Benefit Scale in Slovenia.

Objectives: Timely access to novel anticancer drugs is challenging and value frameworks such as the European Society of Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) could assist in drug prioritization. We assessed the overall time to access to novel anticancer drugs in Slovenia and its correlation with ESMO-MCBS scores.Methods: Anticancer drugs with European Medicines Agency marketing authorization (EMA MA), applying for national reimbursement approval (NRA) in the period 2008-2018 with assigned ESMO-MCBS score, were included. Publically available data from EMA and the Slovenian National Health Insurance Institute were used for time calculations.Results: Among 53 studied drugs; a majority (47) of them obtained reimbursement approval within the observed time. The median time to EMA MA was 397 (range 98-615) days with the NRA requiring additional 422 (range 154-892) days. Neither time to EMA MA nor NRA correlated with ESMO-MCBS substantial clinical benefit (p = 0.332 and p = 0.965, respectively).Conclusions: In Slovenia, time to access to novel anticancer drugs exceeds two years and, more importantly, is equally long for drugs with or without substantial clinical benefit. Integration of the ESMO-MCBS into reimbursement deliberations could improve access to drugs with substantial clinical benefit.

Immunohistochemistry for EGFR Mutation Detection in Non-Small-Cell Lung Cancer.

INTRODUCTION: The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation-positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing. METHODS: The trial included 79 consecutive EGFR mutation-positive and 29 EGFR mutation-negative NSCLC cases diagnosed with reflex PCR-based testing. Two mutation-specific antibodies against the most common exon 19 deletion, namely E746-A750del (clone SP111) and L858R mutation (clone SP125) were tested by using automated immunostainer. Sixty of 79 EGFR mutation-positive cases were treated with EGFR TKIs for advanced disease and included in treatment outcome analysis. A decision tree was used for the cost-effectiveness analysis. RESULTS: The overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 84.8% (95% confidence interval [CI] 74.6-91.6) and 100% (95% CI 85.4-100), respectively. The median progression-free survival (PFS) and overall survival (OS) of patients with IHC-positive EGFR mutation status were highly comparable to the total cohort (PFS: 14.3 vs. 14.0 months; OS: 34.4 vs. 34.4 months). The PCR and IHC cost ratio needs to be approximately 8-to-1 and 4-to-1 in White and Asian populations, respectively, to economically justify upfront use of IHC. CONCLUSION: The trial confirmed an excellent specificity with fairly good sensitivity of IHC with mutation-specific antibodies for common EGFR mutations and the accuracy of IHC testing for predicting response to EGFR TKIs. The use of upfront IHC depends mainly on the population EGFR mutation positivity probability.

Update on systemic therapy of advanced non-small-cell lung cancer.

In the last decade, major progress in the treatment of advanced non-small-cell lung cancer has been made through the better understanding of the molecular biology of lung cancer, identification of new oncogene drivers and development of oncogene-directed drugs. Oncogene-directed therapies with EGFR or anaplastic lymphoma kinase tyrosine kinase inhibitors became standard practice in patients with activating EGFR mutations or anaplastic lymphoma kinase rearrangements, improving median survival rates to up to 35 months. Encouragingly, there are still numerous other targeted drugs and treatment strategies under development. In addition, nowadays chemotherapy can be tailored based on histology of the primary tumor and response to induction chemotherapy, raising median survival rates up to 13 months. These major developments, both in oncogene- and non-oncogene-directed therapies is presented in this review, together with a further designation of the most relevant future strategies, such as immunotherapy.

Oral treatment with etoposide in small cell lung cancer - dilemmas and solutions.

BACKGROUND: Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be at risk for excess toxicity. CONCLUSIONS: The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions (e.g. with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient. Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice.

Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting.

BACKGROUND: Small cell lung cancer (SCLC) represents approximately 13 to 18% of all lung cancers. It is the most aggressive among lung cancers, mostly presented at an advanced stage, with median survival rates of 10 to12 months in patients treated with standard chemotherapy and radiotherapy. In approximately 15-20% of patients brain metastases are present already at the time of primary diagnosis; however, it is unclear how much it influences the outcome of disease according the other metastatic localisation. The objective of this analysis was to evaluate the median survival of SCLC patients treated by specific therapy (chemotherapy and/or radiotherapy) with regard to the presence or absence of brain metastases at the time of diagnosis. PATIENTS AND METHODS: All SCLC patients have been treated in a routine clinical practice and followed up at the University Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana. RESULTS: We found 251 patients eligible for the study. The median age of them was 65 years, majority were male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients (25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmed by a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. All patients received chemotherapy and all patients with confirmed brain metastases received whole brain irradiation (WBRT). The radiotherapy with radical dose at primary tumour was delivered to 27 patients with limited disease and they got 4-6 cycles of chemotherapy. Median overall survival (OS) of 34 patients with brain metastases was 9 months (95% CI 6-12) while OS of 153 patients with metastases in other locations was 11 months (95% CI 10-12); the difference did not reach the level of significance (p = 0.62). As expected, the OS of patients without metastases at the time of primary diagnosis turned out to be significantly better compared to the survival of patients with either brain or other location metastases at the primary diagnosis (15 months vs 9 and 11 months, respectively, p < 0.001). CONCLUSIONS: In our investigated population, the prognosis of patients with extensive SCLS with brain metastases at the primary diagnosis treated with chemotherapy and WBRT was not significantly worse compared to the prognosis of patients with extensive SCLC and metastases outside the brain. In extensive SCLC brain metastases were not a negative prognostic factor per se if the patients were able to be treated appropriately. However, the survival rates of extensive SCLC with or without brain metastases remained poor and novel treatment approaches are needed. The major strength of this study is that it has been done on a population of patients treated in a routine clinical setting.

Impact of ERCC1 expression on treatment outcome in small-cell lung cancer patients treated with platinum-based chemotherapy.

INTRODUCTION: The excision repair cross-complementing 1 (ERCC1) protein is an extensively investigated molecular marker because it may decrease sensitivity to platinum-based chemotherapy. Low ERCC1 expression has already been correlated with better treatment efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy. However, the data on a prognostic and/or predictive value of ERCC1 in small-cell lung cancer (SCLC) are still very limited. METHODS: This retrospective pilot study evaluated the impact of ERCC1 expression levels on response to first-line platinum-based chemotherapy with or without radiotherapy and survival outcomes of 77 SCLC patients. ERCC1 protein expression was determined immunohistochemically in primary tumour tissue. RESULTS: ERCC1 protein expression was positive in 40/77 (51.9%) of our patients. No significant association was found between ERCC1 protein expression and response rate to first-line platinum-based chemotherapy, progression-free survival (PFS), or overall survival (OS), either in the overall population or in patients stratified by disease stage. CONCLUSIONS: In our limited group of 77 SCLC patients, ERCC1 protein expression was not found to correlate with either response rate to platinum-based chemotherapy or survival outcomes. Multi-centric prospective trials using a validated method of ERCC1 determination are mandatory in order to obtain a definitive answer on the predictive value of ERCC1 in SCLC.

Estimation of renal function in lung cancer patients.

INTRODUCTION: In lung cancer patients treated with chemotherapy, renal function is an important parameter to be monitored. Since measurement of renal function with either isotope or creatinine clearance is time consuming and expensive, we evaluated which of the following equations: Cockcroft-Gault (CG), Wright, modification of diet in renal disease equation (MDRD), MDRD adjusted for body surface area (BSA) and chronic kidney disease epidemiology collaboration (CKD-EPI) best resembles endogenous creatinine clearance (ECC) and could therefore replace its measurement in clinical practice. METHODS: 218 lung cancer patients, who had their 24-h creatinine secretion in urine measured prior to the start of any chemotherapy, were included. Estimation of renal function was calculated and compared to ECC. RESULTS: There were no major differences in the performance of the tested equations. Mean percentage error of more than 20% and general underestimation was common to all equations. Wright equation performed best although it describes only 43% of ECC variability. Mean measured ECC was 94 mL/min (95% confidence interval [CI]: 90-98 mL/min) and 90 mL/min for Wright equation (95% CI: 87-93 mL/min) (Supp. Fig. 3). MDRD and CKD-EPI equation performed poorest since they do not include any body size descriptor. Large deviations of differences were observed, with a median standard deviation of more than 20% and deviations from ECC exceeding 100%. Wright equation performed best, whereas, despite their leading role in the detection of renal diseases, the MDRD and CKD-EPI equation performed poorest since they do not include any body size descriptor. In the range of ECC<50 mL/(min×1.73 m(2)), the CG equation most often detected a contraindication for cisplatin use. Differences between ECC and calculated values correlated with patients' weight, BSA and body mass index when these were not included in the equation itself. CONCLUSIONS: In evaluating the renal function of lung cancer patients, equations adjusted for body size descriptors should be preferred. Estimated renal function should be interpreted against the characteristics of patient's body size and special attention is needed when these are reaching the extremes.

The need for medication reconciliation: a cross-sectional observational study in adult patients.

BACKGROUND: Poor communication of drug therapy at care interface often results in medication errors and adverse drug events. Medication reconciliation has been introduced as a measure to improve continuity of patient care. The aim of this cross-sectional observational study was to evaluate the need for medication reconciliation. METHODS: Comprehensive information on pre-admission therapy was obtained by a research pharmacist for adult medical patients, admitted to a teaching hospital, specialised in pulmonary and allergic diseases, in Slovenia. This information was compared with the in-patient and discharge therapies to identify unintentional discrepancies (medication errors) whose clinical significance was determined by an expert panel reaching consensus. RESULTS: Most of the included 101 patients were elderly (median age: 73 years) who had multiple medications. Among their in-patient drugs (880), few discrepancies were a medication error (54/654), half of which were judged to be clinically important. A higher rate was observed in the discharge drug therapy (747): 369 of the identified discrepancies (566) were a medication error, over half of which were judged as clinically important. A greater number of pre-admission drugs, poorly taken medication histories and a greater number of medication errors in in-patient therapy predisposed patients to clinically important medication errors in discharge therapy. CONCLUSIONS: This study provided evidence in a small sample of patients on the discontinuity of drug therapy at patient discharge in a hospital in Slovenia and its implications for patient care. To ensure continuity and safety of patient care, medication reconciliation should be implemented throughout a patient's hospital stay.

Predictive value of multidrug resistance proteins, topoisomerases II and ERCC1 in small cell lung cancer: a systematic review.

In small-cell lung cancer (SCLC), resistance to cancer drugs presents a major problem, limiting the effectiveness of chemotherapy. A better understanding of the molecular biology is essential to improve currently available cytotoxic therapy. Herein, a systematic review of studies evaluating the predictive value of multidrug resistance-associated proteins (MDR1, MRP1, MRP2 and MVP), topoisomerase II and ERCC1 for chemotherapy outcomes is presented. The role of MDR1, MRP1 and MRP2 as predictive markers in SCLC has not yet been elucidated. The majority of studies reported an association between protein or gene expression and response to chemotherapy; however, the evidence is limited to univariate analyses performed in the frame of small retrospective trials. In addition, the largest trial did not confirm an independent predictive value for response rates or survival. Genetic variability may be overseen as a more promising marker. Available data on the predictive value of topoisomerase II are scarce and in contrast to the general idea that higher protein or gene expression correlate with greater chemo-sensitivity. The data on a possible predictive value of ERCC1 are also quite limited; in two retrospective studies, ERCC1 turned out to be a significant predictive marker for survival, but only for limited disease patients. In conclusion, a continuous research, with standardized and validated methodology of markers' determination, should be aspired at all times; a better understanding of the biology of SCLC is of utmost importance to enable personalized therapy and to improve survival rates in this, so far, poorly controlled disease.

Evaluation of clinical interventions made by pharmacists in chemotherapy preparation.

BACKGROUND: Cancer drugs are high risk drugs and medication errors in their prescribing, preparation and administration have serious consequences, including death. The importance of a multidisciplinary approach and the benefits of pharmacists' contribution to cancer treatment to minimise risk have been established. However, the impact of services provided by pharmacists to cancer patient care is poorly studied. This study explored the clinical interventions made by pharmacists in dispensing of chemotherapy doses, and evaluated pharmacists' contribution to patient care. METHODS: Pharmacists at the Chemotherapy Preparation Unit at a tertiary cancer centre in London were shadowed by two research pharmacists during the clinical screening of chemotherapy prescriptions and release of prepared drugs. An expert panel of pharmacy staff rated the clinical significance of the recorded interventions. RESULTS: Twenty-one pharmacists' interventions were recorded during the screening or releasing of 130 prescriptions or drugs. "Drug and therapy" (38%), "clerical" (22%) and "dose, frequency and duration" (19%) related problems most often required an intervention, identifying areas in chemotherapy prescribing that need improvement. The proposed recommendations were implemented in 86% of the cases. Many recorded interventions (48%) were ranked to have had a "very significant" influence on patient care. CONCLUSION: Clinical interventions made by pharmacists had a significant impact on patient care. The integration of pharmacists' technical and clinical roles into dispensing of chemotherapy doses is required for providing high-quality cancer services.