Opioid analgesics prescribing trends 2010-2019 in Slovenia: National database study.

OBJECTIVE: Significant increases in global opioid use have been reported in recent decades. This study analyzed opioid utilization in outpatient care in Slovenia between 2010 and 2019. METHODS: This retrospective cross-sectional study performed a nationwide database analysis of all outpatient opioid analgesic prescriptions based on Slovenian health insurance claims data. Prevalence was defined as the number of recipients prescribed at least one opioid per 1000 inhabitants. Opioid consumption was presented as the total number of dispensed prescriptions per 1000 inhabitants and dispensed defined daily doses (DDD) per 1000 inhabitants for each year analyzed. RESULTS: The age-standardized prevalence of opioid recipients decreased by 21.5% during the study period. Total opioid consumption decreased both in the number of prescriptions (-9.2%) and DDD (-5.4%). Tramadol consumption decreased in terms of the number of prescriptions (-12.2%) and DDD (-2.7%), whereas prescriptions for strong opioids increased (10.2%) and DDDs decreased (-16.2%). The results suggest less intensive prescribing of strong opioids and more intensive prescribing for tramadol. The most frequently used strong opioids were fentanyl and oxycodone/naloxone. CONCLUSIONS: The prevalence of opioid recipients and opioid consumption is decreasing in Slovenia. Further research is needed to understand whether this finding reflects safe use or underuse of these important analgesics.

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.

General antidepressants prescribing trends 2009-2018 in Slovenia: a cross-sectional retrospective database study.

BACKGROUND: Antidepressants are one of the most frequently prescribed groups of medications. The aim of the study was to evaluate the prevalence and patterns of antidepressants prescribed between 2009 and 2018 in Slovenia in different patient-age groups. METHODS: This retrospective cross-sectional study performed a nationwide database analysis of all outpatient antidepressant prescriptions based on Slovenian health claims data. Prevalence was defined as number of recipients prescribed at least one antidepressant per 1000 inhabitants. Antidepressant consumption was presented as total dispensed defined daily doses per year. RESULTS: In 2018, 147,300 patients were prescribed at least one antidepressant. The prevalence had increased by 16% in ten years and by 7.6% in age standardised data. The largest increase in prevalence was seen in the oldest patients (>80 years, 25% increase); of these, antidepressants are now prescribed to 1 in 4. Use of antidepressants had increased by 38%, suggesting longer treatment duration, increase in dose prescribed or both. SSRIs (selective serotonin reuptake inhibitors) were the most prescribed antidepressants (70% share), with escitalopram and sertraline the most commonly prescribed antidepressants. CONCLUSION: The prevalence of antidepressant prescribing and antidepressant consumption is increasing, mainly due to the population ageing and the increasing prescribing in elderly patients.Key PointsThe prevalence of antidepressant prescribing as well as antidepressants' consumption is increasing, reflecting both population ageing and rising prescribing rates.The increase in prevalence and consumption is most dramatic in the oldest patients (over 80 years of age).SSRIs continue to be the most commonly prescribed antidepressants, whilst prescribing of SNRIs is increasing.Future research should focus on evaluating appropriate prescribing of antidepressants (treatment selection, dosage and duration), especially in the elderly.

Anticholinergic Burden in Children, Adults and Older Adults in Slovenia: A Nationwide Database Study.

Anticholinergic burden has been widely studied in specific patient populations with specific conditions. However, the prevalence in the general population is poorly understood. This retrospective cross-sectional study was a nationwide database analysis of outpatient prescriptions of anticholinergic medications. The study was based on Slovenian health claims data of all outpatient prescriptions in 2018. Anticholinergic burden was evaluated using the Anticholinergic Cognitive Burden scale. Three age groups were analysed: children (≤18 years), adults (19-64 years) and older adults (≥65 years). Anticholinergic medications were prescribed to 29.8% of the participants; 7.6% were exposed to a clinically significant anticholinergic burden. The proportion of patients exposed to anticholinergic burden was highest in older adults (43.2%), followed by adults (25.8%) and children (20.7%). The most frequently prescribed medications with the highest anticholinergic activity were antipsychotics and medications for urinary diseases (42.8% and 40.2%, respectively). Medications with second highest activity were mostly antiepileptics (87.3%). Medications with possible anticholinergic activity included diverse therapeutic groups. Anticholinergic burden is highest in older adults but is also considerable among adults and children. Medications with anticholinergic activity belong to diverse therapeutic groups. Further research is needed on safe use of these medications in all age groups.

Pharmacy-supported interventions at transitions of care: an umbrella review.

Background Medication discrepancies arising at care transitions are prevalent and are linked with adverse drug events and increased healthcare utilization. Evidence is lacking about which pharmacy-supported interventions at care transitions are most effective for both the patient and the healthcare system. Aim of the review To invesitigate the content and effect of pharmacy-supported interventions at transitions of care. Method The PubMed, Ovid/Medline and Cochrane Database of Systematic Reviews databases were used. The search was limited to systematic reviews and meta-analyses published in English up to May 2018. Included reviews investigated any intervention related to medication therapy performed by pharmacists or multiple healthcare professionals, including a pharmacist, at transition points in any healthcare setting. Reviews were excluded if interventions were not clearly defined or were not performed at care transitions or were not related to medications. A quality assessment was performed using the PRISMA guidelines. The data extracted included general characteristics, methodology, point of transition, pharmacy-supported interventions and outcomes. For systematic reviews, narrative conclusions were extracted. For meta analyses, reported relative risks or odds ratios were extracted along with the 95% confidence intervals. Results Nine systematic reviews and 5 meta-analyses reporting 162 studies were included. The interventions analysed included medication reconciliation (7 reviews) and composite interventions (7 reviews). Six studies reviewed interventions performed by pharmacists alone, while 8 studies explored interventions by different healthcare professionals, including a pharmacist. A positive effect on either medication discrepancies or (potential) ADEs was observed in all reviews. Mixed effects were observed for hospitalizations rates (9 reviews) and costs (4 reviews), regardless of the intervention applied. Mixed effects were also observed for both medication reconciliation and composite interventions on the number of emergency department visit. Interventions showed no significant effect on mortality (4 reviews). The quality of the reviews showed significant variability. Conclusion Pharmacy-supported interventions at transitions of care are heterogeneous and potentially improve medication safety, but show no significant effect on mortality. The effect on healthcare utilization and costs is inconclusive.

Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia.

BACKGROUND: Sarcopenia was recently recognized as an independent condition by an International Classification of Diseases, Tenth Revision, Clinical Modification code, and is a frequently observed comorbidity in chronic obstructive pulmonary disease (COPD). Muscle mass is primarily dictated by the balance between protein degradation and synthesis, but their relative contribution to sarcopenia is unclear. OBJECTIVE: We aimed to assess potential differential molecular regulation of protein degradation and synthesis, as well as myogenesis, in the skeletal muscle of COPD patients with and without sarcopenia. METHODS: Muscle biopsies were obtained from the vastus lateralis muscle. Patients with COPD were clustered based on sarcopenia defined by low appendicular skeletal muscle mass index (nonsarcopenic COPD, n = 53; sarcopenic COPD, n = 39), and compared with healthy nonsarcopenic controls (n = 13). The mRNA and protein expression of regulators and mediators of ubiquitin-proteasome system (UPS), autophagy-lysosome system (autophagy), and protein synthesis were analyzed. Furthermore, mRNA expression of myogenesis markers was assessed. RESULTS: UPS signaling was unaltered, whereas indices of UPS regulation (eg, FOXO1 protein; p-FOXO3/FOXO3), autophagy signaling (eg, LC3BII/I; p-ULK1[Ser757]/ULK1), and protein synthesis signaling (eg, AKT1; p-GSK3B/GSK3B; p-4E-BP1/4E-BP1) were increased in COPD. These alterations were even more pronounced in COPD patients with sarcopenia (eg, FOXO1 protein; p-FOXO1/FOXO1; LC3BII/I; p-ULK(Ser555); p-AKT1/AKT1; AKT1; p-4E-BP1). Furthermore, myogenic signaling (eg, MYOG) was increased in COPD despite a concomitant increase of myostatin (MSTN) mRNA expression, with no difference between sarcopenic and nonsarcopenic COPD patients. CONCLUSION: Together with elevated myogenic signaling, the increase in muscle protein turnover signaling in COPD, which is even more prominent in COPD patients with sarcopenia, reflects molecular alterations associated with muscle repair and remodeling.

Sarcopenia in Advanced COPD Affects Cardiometabolic Risk Reduction by Short-Term High-intensity Pulmonary Rehabilitation.

OBJECTIVES: Sarcopenia is common in chronic obstructive pulmonary disease (COPD) and may contribute to increased cardiometabolic risk. Interventions to reduce cardiometabolic risk in advanced COPD have been scarcely studied. We have investigated the cardiometabolic effect of a short-term high-intensity rehabilitation program in sarcopenic and nonsarcopenic patients with advanced COPD. DESIGN: Prospective observational study. SETTING: Inpatient 4-week short-term high-intensity pulmonary rehabilitation program at the University Clinic Golnik, Slovenia. PARTICIPANTS: 112 stable COPD patients (66 ± 8 years, 85% GOLD III/IV, 66% men). MEASUREMENTS: Blood biomarkers were assessed at baseline and after rehabilitation. Sarcopenia was assessed at baseline (skeletal muscle index <7.23 kg/m(2) for men and <5.67 kg/m(2) for women, as measured by whole-body dual energy X-ray absorptiometry. Insulin resistance (IR) was defined as homeostasis model assessment of insulin resistance (HOMA-IR) above 2.5. RESULTS: IR and sarcopenia were detected in 59% and 55% of patients, respectively. In contrast to sarcopenic patients, rehabilitation decreased HOMA-IR (2.8 to 1.9, P = .031), fat mass index (10.1 to 9.7 kg/m(2), P = .013), waist circumference (103 to 101 cm, P = .002), and low-density lipoprotein cholesterol (3.2 to 3.0 mmol/L, P = .034) in nonsarcopenic patients. A decrease in total cholesterol levels was observed in both groups. CONCLUSIONS: Sarcopenia affects the modification of cardiometabolic risk markers by short-term high-intensity pulmonary rehabilitation in advanced COPD patients.

The Prevalence of Metabolic Syndrome In Chronic Obstructive Pulmonary Disease: A Systematic Review.

Type 2 Diabetes Mellitus (T2DM) and cardiovascular diseases (CVD) are common in patients with chronic obstructive pulmonary disease (COPD). Prevention of these co-morbidities in COPD requires knowledge on their risk factors. Metabolic syndrome (MetS) predisposes to the development of T2DM and CVD but its prevalence in COPD remains unclear. The aim of this review was to assess the prevalence of MetS and its components in COPD patients compared to controls and to investigate the contribution of clinical characteristics to MetS prevalence. We systematically searched PubMed and EMBASE for original studies in COPD that have investigated the prevalence of MetS and its components. In total, 19 studies involving 4208 COPD patients were included. The pooled MetS prevalence was 34%. Compared to controls, the prevalence was higher in COPD (10 studies, 32% and 30%, p = 0.001). The three most prevalent components in both COPD and controls were arterial hypertension (56% and 51%), abdominal obesity (39% and 38%) and hyperglycemia (44% and 47%). Compared to COPD patients without MetS, those with MetS had higher body mass index (BMI) (29.9 and 24.6 kg/m(2), p < 0.001), higher forced expiratory volume in 1 second (FEV1) % predicted (54 and 51, p < 0.001) and were more frequently female (31% and 25%, p = 0.011). In conclusion, the prevalence of MetS in COPD patients is high and hypertension, abdominal obesity and hyperglycemia are the most prevalent components. Further studies are needed to evaluate the impact of lifestyle factors and medications on MetS in COPD.

A simple dried blood spot method for clinical pharmacological analyses of etoposide in cancer patients using liquid chromatography and fluorescence detection.

BACKGROUND: Therapeutic drug monitoring of etoposide is not part of the routine clinical practice, however, measuring etoposide plasma concentration may be useful to prevent chemotherapy related adverse drug reactions. This paper describes the development and validation of a dried blood spot (DBS) assay for the determination of etoposide in blood samples of lung cancer patients. METHODS: The whole blood spot was cut out of the DBS card followed by sonication assisted liquid drug extraction. Extraction solution was evaporated and re-dissolved. A high-performance-liquid-chromatography method with fluorimetric detection ( λex=230nm; λem=330nm) was used. RESULTS: Method met the validation criteria in terms of selectivity, linearity (0.5-20.0µg/mL), accuracy (≥96.1%), precision (≤10.1%) and stability (long term 4weeks at room temperature and 40°C). Haematocrit did not influence DBS etoposide concentration. Good correlation between measured plasma and DBS concentrations was observed. The equation considering only haematocrit value was used for conversion of DBS to plasma concentration. CONCLUSIONS: DBS sampling method showed comparable results to plasma samples. Therefore, it can be concluded that the developed and validated DBS method, which is more patient-friendly and requires less sample handling, is a reliable alternative to conventional plasma methods for measuring etoposide concentration in clinical pharmacological analyses.