Perspectives of primary care physicians on academic detailing for antimicrobial stewardship: feasibility and impact assessment.

OBJECTIVE: To understand primary care physicians' perspectives on academic detailing from an antimicrobial stewardship team to combat antibiotic overuse for upper respiratory infections and bronchitis in the COVID-19 era, which will help prevent avoidable outpatient visits. METHODS: In this prospective study, 14 female Croatian physicians completed standardized qualitative interviews using a semi-structured guide. The data were analyzed using inductive methodology based on reflexive thematic analysis. We used a theoretically informed approach based on a conceptual framework of healthcare intervention implementability focused on three domains: acceptability, fidelity, and feasibility. RESULTS: We identified six key themes highlighting barriers to changing prescribing practices, with patient pressure and specialist recommendations having an impact on the effectiveness of academic detailing. Despite challenges, primary care physicians described appreciation of direct interaction with evidence-based practices and reported usefulness, effectiveness, and further need for academic detailing. CONCLUSION: This study highlights the complex dynamics involved in implementing healthcare interventions and provides valuable insights for enhancing strategies directed at improving antibiotic prescribing practices. Specifically, our findings emphasize factors influencing behavior changes in physicians' antibiotic prescribing. The authors advocate for a collaborative approach involving community and hospital-based professionals to provide tailored guidance and address questions, ultimately improving prescribing practices.

Pharmacotherapy Problems in Best Possible Medication History of Hospital Admission in the Elderly.

Transfer of care is a sensitive process, especially for the elderly. Polypharmacy, potentially inappropriate medications (PIMs), drug-drug interactions (DDIs), and renal risk drugs (RRDs) are important issues in the elderly. The aim of the study was to expand the use of the Best Possible Medication History (BPMH) and to evaluate polypharmacy, PIMs, DDIs, and inappropriately prescribed RRDs on hospital admission, as well as to determine their mutual relationship and association with patients' characteristics. An observational prospective study was conducted at the Internal Medicine Clinic of Clinical Hospital Dubrava. The study included 383 elderly patients. Overall, 49.9% of patients used 5−9 prescription medications and 31.8% used 10 or more medications. EU(7)-PIMs occurred in 80.7% (n = 309) of the participants. In total, 90.6% of participants had ≥1 potential DDI. In total, 43.6% of patients were found to have estimated glomerular filtration rate < 60 mL/min/1.73 m2, of which 64.7% of patients had one or more inappropriately prescribed RRDs. The clinical pharmacist detected a high incidence of polypharmacy, PIMs, DDIs, and inappropriately prescribed RRDs on hospital admission. This study highlights the importance of early detection of pharmacotherapy problems by using the BPMH in order to prevent their circulation during a hospital stay. The positive correlations between polypharmacy, PIMs, DDIs, and inappropriately prescribed RRDs indicate that they are not independent, but rather occur simultaneously.

Health-Related Quality of Life in Patients with Haemophilia and Its Association with Depressive Symptoms: A Study in Croatia and Slovenia.

BACKGROUND: There are only a few studies in patients with haemophilia (PWH) that examined both quality of life and depressive symptoms, with only few studies examining their association. Aim of this study was to examine the association between depressive symptoms and health-related quality of life (HRQoL) in PWH from Croatia and Slovenia. SUBJECTS AND METHODS: A total of 112 adult PWH on prophylactic (73%) or on-demand (27%) treatment were included in the study (median age 46 years, range 18-73 years). Depressive symptoms were assessed with BDI-II, HRQoL with SF-36v2, demographic and socioeconomic data were collected using a questionnaire, and clinical data were obtained from medical records. RESULTS: All HRQoL scores were significantly negatively correlated with BDI-II in the -0.42 to -0.70 range (all p<0.05). Socio-demographic and clinical variables explained 28-51% of HRQoL variance scores. Depressive symptoms explained additional variance for six HRQoL domain scores, with incremental variance being larger for mental domain scores (ranging between 10-27%), and for Mental Component Summary score (26%). CONCLUSIONS: This study's findings support that having depressive symptoms is associated with HRQoL of PWH, more so in the mental health than in the physical health domains.

Pharmacists' interventions improve health-related quality of life of rural older person on warfarin: a randomized controlled trial.

Warfarin therapy can significantly affect patients' quality of life and cause therapy discontinuation. This study aimed to investigate the effect of the pharmacists' interventions on the health-related quality of life (HRQoL) in older rural patients on warfarin therapy. Eligible older patients from rural area of Croatian province Slavonia were randomized into the intervention and control groups and followed for six months. Repeated education and a follow-up plan were provided to the participants in the intervention group, and if needed, the pharmacist intervened to optimize warfarin therapy. Secondary analysis on HRQoL data are presented here. Main outcome measure was Duke anticoagulation satisfactions scale questionnaire score. In total, 131 participants finished the study (median age 73 years; 51.1% male). Participants in the intervention group scored significantly lower (median being 86.5 and 66.0 in the control and intervention groups, respectively; p < 0,001), indicating higher HRQoL. Adverse drug reactions and pharmacist's intervention were identified as predictive factors for patients' HRQoL (r2 = 65.5%, P < 0.001). The study demonstrated that community pharmacist's interventions can improve HRQoL of older patients taking warfarin what is of particular significance for patients living in rural areas with less accessible healthcare and lower socio-economic status.Clinicaltrials.gov (ID: NCT03212898), 11/07/2017, retrospectively registered.

Patients perspectives on drug shortages in six European hospital settings - a cross sectional study.

BACKGROUND: It is known that drug shortages represent a major challenge for all stakeholders involved in the process, but there is little evidence regarding insights into patients' awareness and perspectives. This study aimed to investigate the patients-perceived drug shortages experience and their view on outcomes in different European hospital settings. Furthermore, we wanted to explore information preferences on drug shortages. METHODS: A retrospective, cross sectional, a mixed method study was conducted in six European hospital settings. One hospital (H) from each of this country agreed to participate: Bosnia and Herzegovina (H-BiH), Croatia (H-CR), Germany (H-GE), Greece (H-GR), Serbia (H-SE) and Poland (H-PO). Recruitment and data collection was conducted over 27 months from November 2017 until January 2020. Overall, we surveyed 607 patients which completed paper-based questionnaire. Questions related to: general information (demographic data), basic knowledge on drug shortages, drug shortages experienced during hospitalization and information preferences on drug shortage. Differences between hospital settings were analyzed using Chi-squared test or Fisher's exact test. For more complex contingency tables, Monte Carlo simulations (N = 2000) were applied for Fisher's test. Post-hoc hospital-wise analyses were performed using Fisher's exact tests. False discovery rate was controlled using the Bonferroni method. Analyses were performed using R: a language and environment for statistical computing (v 3.6.3). RESULTS: 6 % of patients reported experiences with drug shortages while hospitalized which led to a deterioration of their health. The majority of affected patients were hospitalized at hematology and/or oncology wards in H-BiH, H-PO and H-GE. H-BiH had the highest number of affected patients (18.1 %, N = 19/105, p < 0.001) while the fewest patients were in H-SE (1 %, N = 1/100, p = 0.001). In addition, 82.5 %, (N = 501/607) of respondents wanted to be informed of alternative treatment options if there was a drug shortage without a generic substitute available. Majority of these patients (66.4 %, N = 386/501) prefer to be informed by a healthcare professional. CONCLUSIONS: Although drug shortages led to serious medical consequences, our findings show that most of the patients did not perceive shortages as a problem. One possible interpretation is that good hospital management practices by healthcare professionals helped to mitigate the perceived impact of shortages. Our study highlights the importance of a good communication especially between patients and healthcare professionals in whom our patients have the greatest trust.

Impact of an integrated medication reconciliation model led by a hospital clinical pharmacist on the reduction of post-discharge unintentional discrepancies.

WHAT IS KNOWN AND OBJECTIVE: There is no optimal standardized model in the transfer of care between hospitals and primary healthcare facilities. Transfer of care is a critical point during which unintentional discrepancies, that can jeopardize pharmacotherapy outcomes, can occur. The objective was to determine the effect that an integrated medication reconciliation model has on the reduction of the number of post-discharge unintentional discrepancies. METHODS: A randomized controlled study was conducted on an elderly patient population. The intervention group of patients received a medication reconciliation model, led entirely by a hospital clinical pharmacist (medication reconciliation at admission, review and optimization of pharmacotherapy during hospitalization, patient education and counselling, medication reconciliation at discharge, medication reconciliation as part of primary health care in collaboration with a primary care physician and a community pharmacist). Unintentional discrepancies were identified by comparing the medications listed on the discharge summary with the first list of medications prescribed and issued at primary care level, immediately after discharge. The main outcome measures were incidence, type and potential severity of post-discharge unintentional discrepancies. RESULTS AND DISCUSSION: A total of 353 patients were analysed (182 in the intervention and 171 in the control group). The medication reconciliation model, led by a hospital clinical pharmacist, significantly reduced the number of patients with unintentional discrepancies by 57.1% (p < 0.001). The intervention reduced the number of patients with unintentional discrepancies associated with a potential moderate harm by 58.6% (p < 0.001) and those associated with a potential severe harm by 68.6% (p = 0.039). The most common discrepancies were incorrect dosage, drug omission and drug commission. Cardiovascular medications were most commonly involved in unintentional discrepancies. WHAT IS NEW AND CONCLUSION: The integrated medication reconciliation model, led by a hospital clinical pharmacist in collaboration with all health professionals involved in the patient's pharmacotherapy and treatment, significantly reduced unintentional discrepancies in the transfer of care.

Association between reported medication adherence and health-related quality of life in adult patients with haemophilia.

Background Medication adherence is an important issue, not just health-related, for patients with haemophilia. Poor medication adherence to long-term therapies limits the potential of effective treatments to improve patients' health-related quality of life. Objective The aim of this study was to investigate the association of reported medication adherence and health-related quality of life in patients with haemophilia. Setting Data were collected from patients at University Hospital Centre Zagreb, Croatia and at University Medical Centre Ljubljana, Slovenia. Method Adult male patients with severe or moderate haemophilia receiving prophylactic treatment were eligible for the study. Main outcome measure Implementation phase of medication adherence was assessed with the self-reported VERITAS-Pro instrument and health-related quality of life with SF-36v2. Results A total of 82 participants were included in the study (median age was 44.50, range 18-73 years). The majority of our participants reported being adherent to medication (83%). Participants showed better health in the mental health domains and Mental Component Summary than in the physical health domains and Physical Component Summary. After controlling for demographic, socioeconomic and clinical predictors, better reported medication adherence explained an additional 4-6% of better health variance in Bodily Pain and Social Functioning domains and Mental Component Summary. Conclusion We found that reported medication adherence can contribute to better health-related quality of life in patients with haemophilia. Since life with a chronic condition is demanding, it is an important finding that medication adherence to replacement therapy can improve life conditions for patients with haemophilia.

Potentially inappropriate medications involved in drug-drug interactions at hospital discharge in Croatia.

Background The potentially inappropriate medications (PIMs) and drug-drug interactions (DDIs) can significantly affect patient safety in the elderly, especially at transition of health care. Objective The aim of this study is to evaluate PIMs involved in potentially clinically significant DDIs in prescribed pharmacotherapy of elderly patients at hospital discharge. Setting Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia. Method During a 16-month period, the pharmacotherapy data were assessed using Lexicomp Online screening software to identify category C (monitor drug therapy), D (consider therapy modification) and X (avoid combination) DDIs. The European Union (EU)(7)-PIM criteria were applied to detect inappropriately prescribed medications involved in DDIs. Clinical pharmacists obtained data from patients' medical records and patient/caregiver interviews. Main outcome measure The incidence of PIMs involved in potentially clinically significant DDIs. Results A total of 364 consecutive elderly patients were enrolled in the study. The mean number of prescription medications at discharge was 9.3. Overall, 2833 potentially clinically significant DDIs were identified: 2445 (86.3%) of them were category C, 347 (12.3%) category D and 41 (1.4%) were category X interactions. A total of 1164 PIMs were involved in 31.2% of category C interactions, 60.2% of category D interactions and 43.9% of category X interactions. The most frequent PIMs involved in potentially clinically significant DDIs were tramadol, benzodiazepines, moxonidine, vildagliptin and metoclopramide. Conclusion A very high incidence of DDIs in elderly patients and a high incidence of PIMs involved in DDIs was determined at hospital discharge.

Consumption of high-dose statins in patients older than 65 years in the Republic of Croatia in the period 2005 - 2015.

OBJECTIVE: Patients over 65 years of age on high-dose statins are most sensitive to the development of adverse effects of statins. The objective of this study is to analyze the consumption of high-dose statins in this patient group in Croatia in the period of 2005 - 2015. MATERIALS AND METHODS: For the period of January 1, 2005 to December 31, 2015, the Croatian Institute for Health Insurance provided us with the total number of: all insured, insured over 65 years of age, insured using statins, insured using high-dose statins, insured over 65 using statins, insured over 65 using high-dose statins, number of packages dispensed through all community pharmacies for all statins registered in Croatia divided by year and sex. Studied high-dose statins were: simvastatin 40 mg; atorvastatin 40 mg, 60 mg, 80 mg; fluvastatin 80 mg; rosuvastatin 40 mg. The yearly consumption of each form of statin was calculated in DDD/1,000 insured/day and was statistically processed. RESULTS: The consumption of all statins increased by 194%, while the consumption of high-dose statins in patients over 65 increased by 296%. The number of all patients on statin therapy increased by 58%, the number of patients over 65 on statin therapy increased by 87%, and the number of patients over 65 on high-dose statins increased by 326%. 60% of all patients over 65 receiving high-dose statins were women. The most used high-dose statins were atorvastatin and simvastatin. CONCLUSION: Consumption of all statins increased, mostly high-dose statins in the 65+ age group, the most sensitive population for adverse effects. The number of 65+ patients on high-dose statins grew much faster than the general statin user group, thus increasing the risk potential. Women are dominating all age and dose groups of statin users.

Depressive symptoms and adherence to prophylaxis in patients with haemophilia from Croatia and Slovenia.

INTRODUCTION: Adherence to a prophylactic therapy is obligatory to prevent bleeding in patients with haemophilia. It has already been recognized that depression is associated with treatment adherence. AIM: The aim of this study was to examine the prevalence of depressive symptoms in adults with haemophilia using an instrument designed or validated for diagnosing or screening for depression and to investigate the association of symptoms of depression with nonadherence to prophylactic therapy in patients from two East European countries. METHODS: Adult patients with severe or moderate haemophilia receiving prophylaxis were eligible for the study. Depressive symptoms were assessed with BDI-II, adherence with VERITAS-Pro, demographic and socioeconomic data were collected using a questionnaire, and clinical data were obtained from medical records. RESULTS: Final sample included 81 participants (median age was 45 years, range 18-73 years). There were 9 (11%) participants with scores on BDI-II above 14 points, the cut-off score for depressive symptomatology. In general, participants were adherent. However, there were 14 (17%) participants who had scores above 57 points, the cut-off score for nonadherence. There was an association between having depressive symptoms and being nonadherent, and depressive symptoms explained additional variance in adherence after controlling for sociodemographic, psychosocial and clinical characteristics. CONCLUSION: Since there is an association between depressive symptoms and nonadherence, it would be beneficial for both patients and the public health system for screening for depressive symptoms to be included as a part of the treatment protocol.

Pharmacists' influence on adverse reactions to warfarin: a randomised controlled trial in elderly rural patients.

Background Adverse reactions to warfarin may be serious and can lead to hospitalisation or death. Minimising the risk of adverse drug reactions through the intervention of community pharmacists is important for patients receiving warfarin, especially for elderly (≥ 65 years) patients living in rural areas. Objective To evaluate the impact of an intervention by community pharmacists on the risk of adverse drug reactions in elderly rural patients receiving warfarin. Setting: A community pharmacy in a rural area of Croatia. Method We conducted a prospective randomised trial. Eligible patients were recruited at the pharmacy and randomised into one of two groups. The participants were followed up every month for 6 months. Main outcome measure: The incidence and type of adverse drug reactions caused by warfarin and the time-to-event. Results In total, 140 patients were randomized and 131 patients completed the study; 65 patients were in the intervention group. The median age of patients was 73 years of age. The cumulative incidence of adverse drug reactions was significantly lower in the intervention group (6-months rate 29% vs. 85% for intervention and control, respectively; hazard ratio = 0.17, p < 0.001) than in the control group. Factors multivariately associated with the development of adverse drug reactions related to warfarin (p < 0.05) were the absence of pharmaceutical intervention, higher time in therapeutic range, change of warfarin dose, changes in dietary vitamin K intake, and marital status other than married. Conclusion Overall, the pharmacist's intervention significantly prolonged the time to occurrence of adverse drug reactions and reduced their incidence.

Pharmacist's interventions improve time in therapeutic range of elderly rural patients on warfarin therapy: a randomized trial.

Background Community pharmacists can play an important role in optimizing warfarin treatment, which is very important in vulnerable patient groups such as the elderly patients in rural areas. Objective To evaluate the impact of a community pharmacist's interventions on the quality of anticoagulation in elderly rural patients receiving warfarin. Setting A community pharmacy in Donji Miholjac in Croatia's province of Slavonia. Method We conducted a prospective randomized trial. Eligible patients were recruited at the pharmacy and randomized into two groups. All participants were followed up monthly for a period of 6 months. Repeated education and a follow up plan were provided to the participants in the intervention group, and their general practitioners were contacted to correct the warfarin dose or to avoid drug interactions. Main outcome measure Time in therapeutic range (TTR) calculated by the Rosendaal method. Results A total of 140 patients were randomized and 131 patients finished the study, 65 patients in the intervention group. Median age was 73 years. At the end of the follow-up period, the median TTR was significantly higher in the intervention group (93 vs. 31.2% for intervention and control, respectively; P < 0.001). The proportion of patients with TTR ≥ 65% was also significantly higher in the intervention group (86.2 vs. 7.6% for intervention and control, respectively; P < 0.001). Factors independently associated with TTR ≥ 65% were intervention (P < 0.001), less frequent dose change (P = 0.005), better adherence (P < 0.001) and less variable vitamin K intake (P = 0.010).

Potentially inappropriate medicines in elderly hospitalised patients according to the EU(7)-PIM list, STOPP version 2 criteria and comprehensive protocol.

PURPOSE: The aim of this study was to measure the prevalence of potentially inappropriate medications (PIMs) by using the EU(7)-PIM list, STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) version 2 criteria and the new comprehensive protocol. METHODS: This prospective study involved a sample of 276 consecutive elderly patients discharged from the university teaching hospital. Age, gender, diagnoses, medication history and medicines at discharge were recorded. The main outcome measure was the prevalence of PIMs according to each set of criteria: EU(7)-PIM list, STOPP version 2 criteria and comprehensive protocol. RESULTS: The median patient age (range) was 74 (65-92) years. The median number of prescribed medications was 7 (1-17). STOPP identified 393 PIMs affecting 190 patients (69%), EU(7)-PIM list identified 330 PIMs in 184 patients (66.7%) whilst the comprehensive protocol identified 134 PIMs in 102 patients (37%). STOPP version 2 criteria identified significantly more PIMs per patient than the other two protocols (p < 0.001). Gender (p = 0.002), glomerular filtration rate (p = 0.039) and number of comorbidities (p = 0.001) were associated with the proportion of PIMs for the STOPP version 2 criteria only. CONCLUSION: A very high PIM prevalence at discharge was reported suggesting the urgent need for actions to reduce them. STOPP version 2 criteria identified significantly more PIMs than the EU(7)-PIM list and the comprehensive protocol and was found as a more sensitive tool for PIM detection.

Implementation of Venous Thromboembolism Prophylaxis Guidelines in Clinical Practice: A Retrospective Study in Two Croatian Hospitals.

The aim of this study was to evaluate the implementation of the 9th edition of the American College of Chest Physicians (ACCP9) guidelines for prevention of venous thromboembolism in nonsurgical patients in clinical practice in one university and one general Croatian hospital. A retrospective study was conducted at Zadar General Hospital from Zadar and Dubrava University Hospital from Zagreb. Medical charts of all patients admitted to Medical Departments in two periods, before and after implementation of the ACCP9 guidelines, were analyzed. The ACCP9 guidelines were made available to all physicians through the hospital electronic information system immediately after the publication. The Hospital Drug Committees promoted implementation of the guidelines during their periodical clinical visits. Overall, 850 patients were included in the study in two periods. There was no statistically significant difference in the number of high-risk patients receiving thromboprophylaxis after the guidelines implementation in either hospital. In both periods, a signifi-cantly higher number of high-risk patients received thromboprophylaxis in Dubrava University Hos-pital in comparison with Zadar General Hospital (31.7% vs. 3.8% and 40.3% vs. 7.3%, respectively; p<0.001). This study revealed insufficient implementation of evidence-based thromboprophylaxis guidelines in clinical practice in two Croatian hospitals.

Clinical pharmacist-led program on medication reconciliation implementation at hospital admission: experience of a single university hospital in Croatia.

AIM: To evaluate the clinical pharmacist-led medication reconciliation process in clinical practice by quantifying and analyzing unintentional medication discrepancies at hospital admission. METHODS: An observational prospective study was conducted at the Clinical Department of Internal Medicine, University Hospital Dubrava, during a 1-year period (October 2014 - September 2015) as a part of the implementation of Safe Clinical Practice, Medication Reconciliation of the European Network for Patient Safety and Quality of Care Joint Action (PASQ JA) project. Patients older than 18 years taking at least one regular prescription medication were eligible for inclusion. Discrepancies between pharmacists' Best Possible Medication History (BPMH) and physicians' admission orders were detected and communicated directly to the physicians to clarify whether the observed changes in therapy were intentional or unintentional. All discrepancies were discussed by an expert panel and classified according to their potential to cause harm. RESULTS: In 411 patients included in the study, 1200 medication discrepancies were identified, with 202 (16.8%) being unintentional. One or more unintentional medication discrepancy was found in 148 (35%) patients. The most frequent type of unintentional medication discrepancy was drug omission (63.9%) followed by an incorrect dose (24.2%). More than half (59.9%) of the identified unintentional medication discrepancies had the potential to cause moderate to severe discomfort or clinical deterioration in the patient. CONCLUSION: Around 60% of medication errors were assessed as having the potential to threaten the patient safety. Clinical pharmacist-led medication reconciliation was shown to be an important tool in detecting medication discrepancies and preventing adverse patient outcomes. This standardized medication reconciliation process may be widely applicable to other health care organizations and clinical settings.

Adverse drug reactions in elderly patients following discharge from an internal medicine clinic.

OBJECTIVE: The aim of this study was to evaluate the incidence and type of adverse drug reactions (ADRs) and identify risk factors for ADRs in elderly patients within 30 days following discharge from an internal medicine clinic. METHODS: A prospective observational study was conducted at the Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia, between September 1(st) and November 30(th) 2012. Patients aged ≥ 65 years discharged from the clinic during the study period were eligible for inclusion in the study. The follow-up visit was scheduled ~ 30 days after discharge. During the visit, the patients were assessed for the occurrence of ADRs. Two independent physicians evaluated each possible ADR by using the Naranjo ADR probability scale. Multivariate logistic regression analysis was used to identify predisposing factors for ADRs. RESULTS: There were 209 patients included in this study. A total of 72 ADRs were detected in 63 (30.1%) patients. The most frequent ADRs were bleeding disorders associated with warfarin therapy, followed by hypoglycemia associated with antidiabetics. Five (6.9%) ADRs, which resulted in hospital admission, were classified as serious. Multivariate logistic regression analysis indicated number of prescribed drugs ≥4 and prescription of furosemide and warfarin to be associated with increased risk of ADRs. CONCLUSIONS: Our study showed that ADRs are an important cause of morbidity in elderly patients after hospital discharge. Judicious prescription of drugs and careful and frequent monitoring of drug therapy are necessary to reduce the risk of ADRs.

The relationship between methylenetetrahydrofolate reductase C677T gene polymorphism and diabetic nephropathy in Croatian type 2 diabetic patients.

Methylenetetrahydrofolate reductase (MTHFR) polymorphism has been shown to be associated with the development of diabetic nephropathy in many ethnic groups. In this study, we examined the correlation between MTHFR C677T polymorphism and microalbuminuria in patients with diabetes mellitus type 2 in Croatian patients. 85 patients with diabetes mellitus type 2 were recruited. Patients were classified into two groups--with and without diabetic nephropathy according to urinary albumin excretion rate in urine collected during 24 hours. The C677T genotype was determined by real-time PCR analysis. The genotype frequencies were CC 36.5%, CT 42.3% and TT 21.2% in diabetic patients without nephropathy versus CC 39.4%, CT 45.4% and TT 15.2% in those with nephropathy. There was no statistically significant difference in allele distribution between patients with nephropathy and those without (p = 0.788). Our study did not show a correlation between mutations in the MTHFR gene and diabetic nephropathy in Croatian patients. Diabetic nephropathy is influenced by multiple risk factors which can modify the importance of MTHFR polymorphism in its development.

Actual drug-drug interactions in elderly patients discharged from internal medicine clinic: a prospective observational study.

PURPOSE: The aim of the study was to evaluate the incidence and type of actual drug-drug interactions (DDIs) that result in adverse drug reactions (ADRs) or diminished therapeutic effect in elderly patients within 30 days of discharge from an internal medicine clinic. METHODS: A prospective observational study was conducted at the Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia, between October and December 2011. Patients aged ≥ 65 years discharged from the Internal Medicine Clinic during the study period with a prescription for two or more medications were eligible for inclusion in the study. A total of 222 patients were ultimately enrolled in the study. For each patient, potential DDIs were identified using Lexi-Interact software. The follow-up visit was scheduled approximately 30 days after discharge. Causality between DDIs and ADRs or diminished therapeutic effect of drugs was assessed by two independent clinicians. RESULTS: Potential DDIs were identified in 190 (85.6 %) patients. Actual DDIs were detected in 21 (9.5 %) patients. In 19 patients, DDIs resulted in an ADR. Diminished therapeutic effect resulting from DDIs was detected in two patients. Angiotensin-converting enzyme inhibitors were the drug class most frequently associated with DDI-related ADRs. CONCLUSIONS: A significant incidence of actual DDIs suggests that DDIs play an important role in patient safety. Drug therapy should be initiated if absolutely necessary, and the number of drugs used to treat elderly patients should be minimized to reduce the incidence of DDI-related adverse patient outcomes.

Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing acute respiratory infections in children. It results in about 3.4 million hospitalisations annually in children under five. Palivizumab is an anti-RSV monoclonal antibody, administered intramuscularly at a dose of 15 mg/kg once every 30 days. The efficacy and safety of palivizumab has been evaluated in multicentre, randomised controlled trials (RCTs) and a large number of economic evaluations (EEs) have tested its cost-effectiveness. OBJECTIVES: To assess the effectiveness and safety of palivizumab prophylaxis compared with placebo, or another type of prophylaxis, in reducing the risk of complications (hospitalisation due to RSV infection) in high-risk infants and children. To assess the cost-effectiveness (or cost-utility) of palivizumab prophylaxis compared with no prophylaxis in infants and children in different risk groups. SEARCH METHODS: We searched CENTRAL 2012, Issue 7, MEDLINE (1996 to July week 4, 2012), EMBASE (1996 to August 2012), CINAHL (1996 to August 2012) and LILACS (1996 to August 2012) for studies of effectiveness and safety. We searched the NHS Economic Evaluations Database (NHS EED 2012, Issue 4), Health Economics Evaluations Database (HEED, 9 August 2012) and Paediatric Economic Database Evaluations (PEDE, 1980 to 2009), MEDLINE (1996 to July week 4, 2012) and EMBASE (1996 to August 2012) for economic evaluations. SELECTION CRITERIA: We included RCTs comparing palivizumab prophylaxis with a placebo, no prophylaxis or another type of prophylaxis in preventing serious lower respiratory tract disease caused by RSV in paediatric patients at high risk. We included cost-effectiveness analyses and cost-utility analyses comparing palivizumab prophylaxis with no prophylaxis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias for the included studies and extracted data for both the RCTs and EEs. We calculated risk ratios (RRs) and their associated 95% confidence intervals (CIs) for dichotomous outcomes and for adverse events (AEs). We provided a narrative summary of results for continuous outcomes, due to missing data on standard deviations. We performed fixed-effect meta-analyses for the estimation of pooled effects whenever there was no indication of heterogeneity between included RCTs. We summarised the results reported in included EEs, such as incremental costs, incremental effectiveness, and incremental cost-effectiveness and/or cost-utility ratios (ICERs), and we calculated ICER present values in 2011 Euros for all studies. MAIN RESULTS: Of the seven available RCTs, three compared palivizumab with a placebo in a total of 2831 patients, and four compared palivizumab with motavizumab in a total of 8265 patients. All RCTs were sponsored by the drug manufacturing company. The overall quality of RCTs was good, but for most of the outcomes assessed only data from two studies contributed to the analysis. Palivizumab prophylaxis was associated with a statistically significant reduction in RSV hospitalisations (RR 0.49, 95% CI 0.37 to 0.64) when compared to placebo. When compared to motavizumab, palivizumab recipients showed a non-significant increase in the risk of RSV hospitalisations (RR 1.36, 95% CI 0.97 to 1.90). In both cases, the proportion of children with any AE or any AE related to the study drug was similar between the two groups.In terms of economic evidence, we included 34 studies that reported cost-effectiveness and/or cost-utility data for palivizumab prophylaxis compared with no prophylaxis, in high-risk children with different underlying medical conditions. The overall quality of EEs was good, but the variations in modelling approaches were considerable across the studies, leading to big differences in cost-effectiveness results. The cost-effectiveness of palivizumab prophylaxis depends on the consumption of resources taken into account by the study authors; and on the cost-effectiveness threshold set by the healthcare sector in each country. AUTHORS' CONCLUSIONS: There is evidence that palivizumab prophylaxis is effective in reducing the frequency of hospitalisations due to RSV infection, i.e. in reducing the incidence of serious lower respiratory tract RSV disease in children with chronic lung disease, congenital heart disease or those born preterm.Results from economic evaluations of palivizumab prophylaxis are inconsistent, implying that economic findings must be interpreted with caution. ICER values varied considerably across studies, from highly cost-effective to not cost-effective. The availability of low-cost palivizumab would reduce its inequitable distribution, so that RSV prophylaxis would be available to the poorest countries where children are at greatest risk.

The effect of pharmacotherapeutic counseling on readmissions and emergency department visits.

OBJECTIVE: To evaluate the impact of pharmacotherapeutic counseling on the rates and causes of 30-day post-discharge hospital readmissions and emergency department visits. SETTING: The study was conducted at the Medical Clinic of University Hospital Dubrava, Zagreb, Croatia. METHODS: The study included elderly patients prescribed with two or more medications for the treatment of chronic diseases. The patients randomized into the intervention group received pre-discharge counseling by the clinical pharmacologist about each prescribed medication. The control group received no counseling. MAIN OUTCOME MEASURES: The rates and causes of 30-day postdischarge hospital readmissions and emergency department visits. Medication compliance was also evaluated, using the pill count method. RESULTS: A total of 160 patients were randomly selected for the study. No significant difference was found in the readmission and emergency department visit rates between the intervention and control groups (p = 0.224). There were 34.9 % more compliant patients in the intervention group. Significantly more non-compliant patients in the control group were readmitted or visited emergency department because of the disease progression (p = 0.031). In the intervention group, significantly more patients were readmitted or visited emergency department because of an adverse drug reaction (p = 0.022). CONCLUSION: Pharmacotherapeutic counseling can reduce readmission and emergency department visit rates for disease progression. Improved patient knowledge about adverse drug reactions could be the reason for increased rates of readmissions and emergency department visits due to adverse drug reactions in the intervention group.