Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study.

PURPOSE: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. METHODS: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. RESULTS: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from -39.4% in Romagna to -14.2% in Scotland) and nasal preparations (from -34.4% in Lithuania to -5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. CONCLUSIONS: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas.

Use of healthcare resources and drug expenditure before and after treatment of chronic hepatitis C with direct antiviral agents.

The aim of this study was to analyse the impact of treating chronic hepatitis C (CHC) with direct-acting agents (DAA) on the use of healthcare resources. We included all patients treated with DAA for CHC from January 2015 to December 2017 in Catalonia whose medical records from 12 months before to 24 months after treatment were available. Data were obtained from the Catalan Health Surveillance System. A total of 12,199 patients in Catalonia were treated with DAA for CHC. Of these, 11.3% had no-minimal fibrosis (F0-F1), 24.0% had moderate fibrosis (F2), 50.3% had significant fibrosis or cirrhosis (F3-F4), and 14.4% had decompensated cirrhosis. Use of healthcare resources decreased from the pre-treatment period to the post-treatment period for the following: hospital admissions due to complications of cirrhosis, from 0.19 to 0.12 per month per 100 patients (RR 0.57; 95% CI 0.47-0.68); length of hospital stay, from 12.9 to 12.2 days (RR 0.93; 95% CI 0.91-0.94); outpatient visits, from 65.0 to 49.2 (RR 0.75; 95% CI 0.74-0.75); and number of medication containers per patient per month, from 13.9 to 12.5 (RR 0.837; 95% CI 0.835-0.838). However, the number of invoices for antineoplastic treatment increased after DAA treatment, especially for patients with high morbidity or advanced fibrosis stage. In conclusion, a decrease in health resource use was seen in CHC patients treated with DAA, as measured by length of hospital stay, number of admissions due to cirrhosis complications, outpatient visits and overall drug invoicing. However, use of antineoplastic drugs increased significantly, especially in patients with cirrhosis and high morbidity.

Description of the use of multicriteria to support pricing and reimbursement decisions by European health technology assessment bodies.

BACKGROUND: Heterogeneity in drug access throughout Europe may be influenced by differences in drug-assessment strategies. The EUnetHTA's assessment core model (EUnetHTA-core) and the EVIDEM's multicriteria framework are reference methodologies in this context, the latter including a wider compromise between non-contextual and contextual criteria. Compliance of 37 European Health Technology Assessment bodies (HTAb) with EUnetHTA-core has been reported, but the use of EVIDEM by this HTAb is still unknown. METHODS: To describe the uptake and use of multicriteria approaches to evaluate drug value by European HTAb using EVIDEM as reference framework, a multicriteria framework was obtained based on EVIDEM model. The criteria used for drug appraisal by HTAb was extracted from the EUnetHTA report, and completed through search of websites, publications and HTAb reports. Use of EVIDEM assessment model in 37 European HTAb has been described semi-quantitatively and summarized using an alignment heatmap. RESULTS: Aligned, medium or misaligned profiles were seen for 24,3%, 51,4% and 24,3% of HTAb when matching to EVIDEM dimensions and criteria was considered. HTAb with explicit responsibilities in providing specific advice on reimbursement showed more aligned profiles on contextual and non-contextual dimensions. CONCLUSIONS: EUnetHTA's core model is limited in assessing medicines while EVIDEM's framework provides contextual dimension used by some HTAb in Europe that can be escalated to other agencies. Most of the 37 European HTAb have room to broaden their contextual assessment tools, especially when social and medical perception of need requires to be explicit to support payer's decision on reimbursement.

Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020.

BackgroundSeveral clinical trials have assessed the protective potential of chloroquine and hydroxychloroquine. Chronic exposure to such drugs might lower the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or severe coronavirus disease (COVID-19).AimTo assess COVID-19 incidence and risk of hospitalisation in a cohort of patients chronically taking chloroquine/hydroxychloroquine.MethodsWe used linked health administration databases to follow a cohort of patients with chronic prescription of hydroxychloroquine/chloroquine and a control cohort matched by age, sex and primary care service area, between 1 January and 30 April 2020. COVID-19 cases were identified using International Classification of Diseases 10 codes.ResultsWe analysed a cohort of 6,746 patients (80% female) with active prescriptions for hydroxychloroquine/chloroquine, and 13,492 controls. During follow-up, there were 97 (1.4%) COVID-19 cases in the exposed cohort and 183 (1.4%) among controls. The incidence rate was very similar between the two groups (12.05 vs 11.35 cases/100,000 person-days). The exposed cohort was not at lower risk of infection compared with controls (hazard ratio (HR): 1.08; 95% confidence interval (CI): 0.83-1.44; p = 0.50). Forty cases (0.6%) were admitted to hospital in the exposed cohort and 50 (0.4%) in the control cohort, suggesting a higher hospitalisation rate in the former, though differences were not confirmed after adjustment (HR: 1·46; 95% CI: 0.91-2.34; p = 0.10).ConclusionsPatients chronically exposed to chloroquine/hydroxychloroquine did not differ in risk of COVID-19 nor hospitalisation, compared with controls. As controls were mainly female, findings might not be generalisable to a male population.

Risk of colorectal cancer in users of bisphosphonates: analysis of population-based electronic health records.

The use of bisphosphonates has been associated with a decrease in the risk of colorectal cancer (CRC) in observational studies, but with controversial results and difficult to interpret because of routine concomitant use of calcium and vitamin D. We aimed to assess the association between CRC risk and outpatient exposure to antiosteoporotic drugs using a large cohort with prescription data in Catalonia. A case-control study was performed using the Information System for Development of Primary Care Research (SIDIAP) which is a primary care medical record database that has linked data on reimbursed medication. The study included 25,836 cases with an incident diagnosis of CRC between 2010 and 2015 and 129,117 matched controls by age (± 5 years), sex and healthcare region. A multivariable model was built adjusting for known risk factors and comorbidities that were significantly associated to CRC in the dataset, and a propensity score for bisphosphonates. Tests for interaction for multiple drug use and stratified analysis for tumour location were prospectively planned. Overall 18,230 individuals (11.5%) were users of bisphosphonates. A significant but modest protective effect on CRC was observed for bisphosphonates (OR 0.95, 95% CI 0.91-0.99), that was no longer significant when adjusted for calcium and vitamin D (OR 0.98, 95% CI 0.93-1.03). Bisphosphonates, however, showed a dose-response effect with duration of use even when adjusted for calcium and vitamin D (OR for use > 40 months: 0.90, 95% CI 0.81-1.00, P value for trend: 0.018). The use of bisphosphonates was associated with a modest decrease in the risk of CRC, but this effect was essentially explained by concomitant use of calcium or vitamin D. The observed protective effect was stronger for long durations of use, which deserves further study.

Ultrasound Assessment of Psoriatic Onychopathy: A Cross-sectional Study Comparing Psoriatic Onychopathy with Onychomycosis.

This cross-sectional study evaluated the usefulness of an ultrasound technique in assessment of nail changes in 35 patients with psoriatic onychopathy and 25 with nail dystrophy secondary to onychomycosis. All patients underwent 3 examinations: a complete clinical assessment; a nail ultrasound study; and fungal culture. Nails of patients with psoriatic onychopathy presented a thinner nail plate and nail bed, measured by ultrasound, than did those with onychomycosis. The percentage of patients with a power Doppler signal ?2 at nail bed was significantly higher in psoriatic onychopathy than in onychomycosis, and structural bone lesions were more frequent in psoriatic onychopathy than in onychomycosis. These results suggest that the presence of structural damage and high-power Doppler signal are the main ultrasound findings supporting a diagnosis of psoriatic onychopathy.

Effects of bupivacaine or levobupivacaine on cerebral oxygenation during spinal anesthesia in elderly patients undergoing orthopedic surgery for hip fracture: a randomized controlled trial.

BACKGROUND: Bupivacaine and levobupivacaine have similar pharmacokinetic and pharmacodynamic characteristics, and are used regularly in spinal anesthesia. Whether potential differences in their hemodynamic and anesthetic profiles could determine a differential risk of complications in elderly subjects, is controversial. The main objective was to compare the effects of intrathecally administered levobupivacaine (LB) versus bupivacaine (B), on regional cerebral O2 saturation during spinal anesthesia, cognitive status and neurological complications in elderly patients undergoing surgery for hip fracture. METHODS: This was a randomized, controlled, single blind study. 58 patients aged 70 or older undergoing surgery for hip fracture with spinal anesthesia were allocated with a 1:1 ratio to receive LB or B, combined with fentanyl 15 µg, by intrathecal route. The primary outcome was the proportion of intraoperative time with regional cerebral desaturation (≥20% reduction in regional cerebral oxygen saturation from baseline), monitored by near -infrared spectroscopy. Secondary endpoints included hemodynamic parameters, level of sensory and motor block, changes in Short Portable Mental Status Questionnaire (SPMSQ), and neurological complications. RESULTS: The mean percentage of intraoperative time with desaturation in the B group was 6.1% (SD: 17.5) and 4.7% (SD: 11.9) in the left and right hemisphere respectively; in the LB group the mean was 4.8% (SD: 11.4) in the left hemisphere and 2.4% (SD: 8.3) in the right one. No statistically significant differences were found between treatment groups. The level of sensory block at the start of surgery was lower for LB than for B (Th10 vs Th8, p:0.047) and motor block at 15 min was lower for LB (2.5 vs 3, p:0.009). No differences in postoperative SPMSQ were observed. Neurological complications such as confusional state, agitation or disorientation were reported in 50% of patients in the B group and 21.4% of patients in the LB group, p = 0.05. CONCLUSIONS: No statistically significant differences in regional cerebral oxygen saturation or hemodynamic parameters were observed between both treatment groups. Bupivacaine and levobupivacaine differed in sensory and motor block achieved. While no differences were observed in cognitive impairment measured by the SPMSQ between treatment groups neurological complications reported by the physician were more frequent with bupivacaine. TRIAL REGISTRATION: European Union Clinical Trials Register ( EudraCT 2013-000846 -20 ) (April 9th, 2013). ClinicalTrials.gov ( NCT01960543 ) (September 23rd, 2013).

Randomized clinical trial to compare the efficacy to improve the quality of surgical field of hypotensive anesthesia with clonidine or dexmedetomidine during functional endoscopic sinus surgery.

PURPOSE: Intense bleeding of the surgical field is a potential factor influencing success of functional endoscopic sinus surgery (FESS). Hypotensive anesthesia with α2 intravenous agonists reduces intraoperative bleeding, but which is the best agent is unknown. The main objective of this trial was to compare the current standard adjuvant drug for hypotensive anesthesia, clonidine, with the recently available alternative dexmedetomidine. METHODS: A randomized clinical trial compared the efficacy of clonidine and dexmedetomidine during FESS. Treatment was open label for the anesthesiologist and operating surgeon, but blind for an external evaluator who evaluated video-recorded surgeries. A Boezaart scale was assessed every 30 min during FESS until surgery completion. Main end-point was the proportion of patients with mean Boezaart scores > 2 (heavy bleeding) by external blinded evaluator. Secondary end-points included other bleeding parameters, surgery duration, hemodynamic measures and surgical complications. RESULTS: 94 patients were randomized. There were no significant differences in the proportion of patients with mean Boezaart scores > 2 in clonidine (42.6%) and dexmedetomidine (42.6%). Consistently, no differences were observed in secondary variables of bleeding, duration or complications. Small differences in mean heart rate were observed that might reflect different pharmacological profiles of the products, but are of uncertain clinical relevance. CONCLUSIONS: No significant differences were observed between clonidine and dexmedetomidine when used as anesthetic adjuvants in the reduction of surgical bleeding in FESS. A longer experience with clonidine and its lower costs suggest it may be a preferable option as an adjuvant for hypotensive anesthesia.

The impact of parallel regulatory-health technology assessment scientific advice on clinical development. Assessing the uptake of regulatory and health technology assessment recommendations.

AIMS: The parallel regulatory-health technology assessment scientific advice (PSA) procedure allows manufacturers to receive simultaneous feedback from both EU regulators and health technology assessment (HTA) bodies on development plans for new medicines. The primary objective of the present study is to investigate whether PSA is integrated in the clinical development programmes for which advice was sought. METHODS: Contents of PSA provided by regulators and HTA bodies for each procedure between 2010 and 2015 were analysed. The development of all clinical studies for which PSA had been sought was tracked using three different databases. The rate of uptake of the advice provided by regulators and HTA bodies was assessed on two key variables: comparator/s and primary endpoint. RESULTS: In terms of uptake of comparator recommendations at the time of PSA in the actual development, our analysis showed that manufacturers implemented comparators to address both the needs of regulators and of at least one HTA body in 12 of 21 studies. For primary endpoints, in all included studies manufacturers addressed both the needs of the regulators and at least one HTA body. CONCLUSIONS: One of the key findings of this analysis is that manufacturers tend to implement changes to the development programme based on both regulatory and HTA advice with regards to the choice of primary endpoint and comparator. It also confirms the challenging choice of the study comparator, for which manufacturers seem to be more inclined to satisfy the regulatory advice. Continuous research efforts in this area are of paramount importance from a public health perspective.

Preoperative management of colorectal cancer-induced iron deficiency anemia in clinical practice: data from a large observational cohort.

BACKGROUND: Preoperative anemia prevalence among colorectal cancer (CRC) patients is high and may adversely influence postoperative outcome. This study assesses the efficacy of a preoperative anemia managing protocol in CRC. STUDY DESIGN AND METHODS: This was a retrospective analysis of consecutive CRC resections at two Spanish centers (January 2012 to December 2013). Preoperative anemia was defined as a hemoglobin (Hb) level of less than 13 g/dL and treated with intravenous iron (IVI) or standard care (oral iron or no iron). Red blood cell transfusion (RBCT) requirements was the primary outcome variable. Postoperative infection rate and length of hospital stay (LOS) were secondary outcome variables. Patients were managed with a restrictive transfusion trigger (Hb < 8 g/dL). Infection was diagnosed clinically and confirmed by laboratory, microbiologic, and/or radiologic evidence. RESULTS: Overall, 322 of 571 patients (56%) presented with anemia: 232 received IVI and 90 standard care. There were differences in RBCT rate between no anemia and anemia (2% vs. 16%; p < 0.01), but not in postoperative infections (19% vs. 22%; p = NS) or LOS. Compared to those on standard care, anemic patients on IVI presented with lower Hb (10.8 g/dL vs. 12.0 g/dL; p < 0.001) at baseline, but similar Hb on day of surgery and Postoperative Day 30. There were no between-group differences in RBCT rates (16% vs. 17%; p = NS), but infection rates were lower among IVI-treated patients (18% vs. 29%; p < 0.05). No relevant IVI-related side effects were recorded. CONCLUSION: Compared to standard care, IVI was more effective in treating preoperative anemia in CRC patients and appeared to reduce infection rate, although it did not reduce postoperative RBCT.

Piperacillin population pharmacokinetics in critically ill patients with multiple organ dysfunction syndrome receiving continuous venovenous haemodiafiltration: effect of type of dialysis membrane on dosing requirements.

OBJECTIVES: This multicentre study aimed to describe the pharmacokinetics (PK) of piperacillin in critically ill patients with multiple organ dysfunction syndrome (MODS) receiving continuous venovenous haemodiafiltration (CVVHDF), to identify the sources of PK variability and evaluate different dosing regimens to develop recommendations based on clinical parameters. PATIENTS AND METHODS: Nineteen patients with MODS and CVVHDF receiving piperacillin/tazobactam were enrolled from three tertiary hospitals (95 plasma samples). Population PK modelling and Monte Carlo simulations were performed using NONMEM v7.3(®). RESULTS: Patients' median age was 70 years (range 39-82), median weight was 80 kg (45-129), median APACHE II score at admission was 21 (13-33) and median SOFA score on the day of study was 11 (8-21). The final population PK model was characterized by CL (L/h) = 6.11 * [weight (kg)/80](1.39) * CLMEMB. If membrane = 1.5 m(2) AN69ST, CLMEMB = 1; if membrane = 0.9 m(2) AN69, CLMEMB = 0.51. Monte Carlo simulations showed that: (i) to maintain unbound piperacillin concentrations above the MIC for the bacteria for 100% of dosing interval T (100%fuT>MIC), patients receiving CVVHDF with 1.5 m(2) AN69ST membranes required doses of 4000 mg q8h for the treatment of bacteria with a susceptibility to piperacillin close to the clinical breakpoint (MIC = 8-16 mg/L) (2000 mg q8h was sufficient for patients with CVVHDF using 0.9 m(2) AN69 membranes); and (ii) for the treatment of bacteria with high susceptibility to piperacillin (MIC <4 mg/L) or for the attainment of a more traditional pharmacodynamic target (50%fuT>MIC), 2000 mg q8h sufficed regardless of type of membrane and body weight. CONCLUSIONS: Our results suggest that type of membrane and body weight should be considered for piperacillin dose titration in critically ill patients with MODS and CVVHDF requirement.

Outpatient multimodal intravenous analgesia in patients undergoing day-case surgery: description of a three year experience.

BACKGROUND: The use of elastomeric devices for ambulatory intravenous pain treatment in Major Ambulatory Surgery (MAS) has been described to improve postoperative pain management. The objective of the study was to describe the first 3 years experience of the use of elastomeric devices for ambulatory intravenous pain treatment in MAS implemented at our site since 2010. METHODS: Data were retrieved from the medical records for all patients who, between January 2010 and March 2014, underwent surgical procedures at the ambulatory surgical centre at our hospital and were prescribed a home-based continuous intravenous analgesia. RESULTS: Data were retrieved from the medical records of 1128 patients. The most frequent surgical interventions included orthopedic and proctology surgeries. 80 % of patients were discharged home without pain; during the first 48 h after discharge roughly 40 % of subjects were completely free of pain, 50 % reported mild pain (VAS 1 to 3) and 9 % reported higher pain scores (4 and above). Peripheral nerve block was associated to better pain control in the immediate postoperative period. Vomiting in the first 24 h was 4.6 % before introducing haloperidol into the drug schemes, and 2.6 % thereafter. Complications related with the intravenous route required treatment withdrawal in 1.1 % cases. Only 3.5 % of patients returned to the hospital in the first 72 h, mainly for non-pain related reasons. Overall, 99.5 % of patients were satisfied with the treatment received at home. CONCLUSION: Our initial experience suggest that outpatient multimodal intravenous analgesia in patients undergoing day-case surgery is a feasible alternative in our setting, that allows an effective management of postoperative pain with a small rate of adverse events and complications requiring readmission.

Meropenem population pharmacokinetics in critically ill patients with septic shock and continuous renal replacement therapy: influence of residual diuresis on dose requirements.

Meropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (CRRT) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. This multicenter study aimed to describe the pharmacokinetics (PKs) of meropenem in this population to identify the sources of PK variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. Thirty patients with septic shock and CRRT receiving meropenem were enrolled (153 plasma samples were tested). A population PK model was developed with data from 24 patients and subsequently validated with data from 6 patients using NONMEM software (v.7.3). The final model was characterized by CL = 3.68 + 0.22 · (residual diuresis/100) and V = 33.00 · (weight/73)(2.07), where CL is total body clearance (in liters per hour), residual diuresis is the volume of residual diuresis (in milliliters per 24 h), and V is the apparent volume of distribution (in liters). CRRT intensity was not identified to be a CL modifier. Monte Carlo simulations showed that to maintain concentrations of the unbound fraction (fu ) of drug above the MIC of the bacteria for 40% of dosing interval T (referred to as 40% of the ƒ uT >MIC), a meropenem dose of 500 mg q8h as a bolus over 30 min would be sufficient regardless of the residual diuresis. If 100% of the ƒ uT >MIC was chosen as the target, oligoanuric patients would require 500 mg q8h as a bolus over 30 min for the treatment of susceptible bacteria (MIC < 2 mg/liter), while patients with preserved diuresis would require the same dose given as an infusion over 3 h. If bacteria with MICs close to the resistance breakpoint (2 to 4 mg/liter) were to be treated with meropenem, a dose of 500 mg every 6 h would be necessary: a bolus over 30 min for oligoanuric patients and an infusion over 3 h for patients with preserved diuresis. Our results suggest that residual diuresis may be an easy and inexpensive tool to help with titration of the meropenem dose and infusion time in this challenging population.

Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy.

Although early and appropriate antibiotic therapy remains the most important intervention for successful treatment of septic shock, data guiding optimization of beta-lactam prescription in critically ill patients prescribed with continuous renal replacement therapy (CRRT) are still limited. Being small hydrophilic molecules, beta-lactams are likely to be cleared by CRRT to a significant extent. As a result, additional variability may be introduced to the per se variable antibiotic concentrations in critically ill patients. This article aims to describe the current clinical scenario for beta-lactam dosing in critically ill patients with septic shock and CRRT, to highlight the sources of variability among the different studies that reduce extrapolation to clinical practice, and to identify the opportunities for future research and improvement in this field. Three frequently prescribed beta-lactams (meropenem, piperacillin and ceftriaxone) were chosen for review. Our findings showed that present dosing recommendations are based on studies with drawbacks limiting their applicability in the clinical setting. In general, current antibiotic dosing regimens for CRRT follow a one-size-fits-all fashion despite emerging clinical data suggesting that drug clearance is partially dependent on CRRT modality and intensity. Moreover, some studies pool data from heterogeneous populations with CRRT that may exhibit different pharmacokinetics (for example, admission diagnoses different to septic shock, such as trauma), which also limit their extrapolation to critically ill patients with septic shock. Finally, there is still no consensus regarding the %T>MIC (percentage of dosing interval when concentration of the antibiotic is above the minimum inhibitory concentration of the pathogen) value that should be chosen as the pharmacodynamic target for antibiotic therapy in patients with septic shock and CRRT. For empirically optimized dosing, during the first day a loading dose is required to compensate the increased volume of distribution, regardless of impaired organ function. An additional loading dose may be required when CRRT is initiated due to steady-state equilibrium breakage driven by clearance variation. From day 2, dosing must be adjusted to CRRT settings and residual renal function. Therapeutic drug monitoring of beta-lactams may be regarded as a useful tool to daily individualize dosing and to ensure optimal antibiotic exposure.

Prevalence of use of on-label and off-label psychotropics in the Greek pediatric population.

With a global increased use of psychotropics in pediatrics, their off-label use is a concern due to uncertainty and risk. Data on psychotropics use in the Greek pediatric population do not exist to date. We analyzed retrospective data from the nationwide pharmacy claim database, to estimate the prevalence of psychotropics in pediatrics focusing on off-label use (March 2016-October 2019). In total 63,782 pediatric subjects had at least one identified psychotropic prescription. The prevalence of psychotropics use was 5.1-14.6/1,000 pediatric inhabitants. When excluding 42,508 subjects who received only short-time hydroxyzine, the prevalence was 3.1-6.5/1,000 pediatric inhabitants; adolescents and boys had higher exposures. An in-depth analysis of 21,274 subjects accounting for 222,307 psychotropic dispensations, showed antiepileptics as the most frequent psychotropics, consistently with the finding on epilepsy being the most frequent diagnosis; diazepam was the single drug with the highest exposure in almost all ages. 14% of subjects have received at least one medicine with no pediatric information in the labelling, corresponding to 5.5% of dispensed psychotropics. 7.6% of all dispensed psychotropics were used in a non-authorized age range with quetiapine being the most frequent psychotropic as off-label age range; antipsychotics and antidepressants were first as off-label for non-authorized indication. Data from Greece show that a relevant number of patients are prescribed psychotropics, with 1 in 7 being under off-label use. Due to the limitations inherent to pharmacy claims databases, further research using clinical data for a longer follow-up period could confirm and identify trends in psychotropics use in Greece.

Long-term impact of COVID-19 pandemic on antibiotic use in primary care: lessons to optimize antimicrobial use.

BACKGROUND: Lockdowns due to the COVID-19 pandemic was associated with changes in the pattern of use of antimicrobials, but persistence of changes after lockdowns has not been described. The objective was to describe the number of patients with dispensed antibiotic treatment and consumption of antibiotics in outpatients from primary care in Catalonia 18 months after the end of the emergency period. RESEARCH DESIGN AND METHODS: Data for the COVID-19 pandemic period was obtained from March 2020 to December 2021. Four high transmission rate (Rt > 100) periods were established. To compare data, a simple Bayesian structural time series model was used. RESULTS: The observed number of patients with dispensed antibiotics decreased respect to the estimated, especially during the four high transmission rate periods: April-May 2020 (lockdown period) (-42.57% and -42.68%); December 2020-February 2021 (-41.65%, -49.97% and -43.64%); October 2021 (-16.23%), and December 2021 (-20.16%). Overall antibiotic consumption was reduced by 23.37% (p = 0.002). These differences were mainly observed in those ≤ 15 years. CONCLUSIONS: We describe the reduction in the number of patients with dispensed antibiotics and antibiotic consumption after the COVID-19 lockdown persisted in a period of recovery of healthcare accessibility. This information may help to improve antimicrobial use at the primary care level.

Incidence of Liver and Non-liver Cancers After Hepatitis C Virus Eradication: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Direct-acting antivirals (DAAs) offer a high rate of hepatitis C virus (HCV) eradication. However, concerns on the risk of cancer after HCV eradication remain. Our study aimed at quantifying the incidence of cancer in patients treated with anti-HCV therapies in Catalonia (Spain) and their matched controls. METHODS: This was a population-based study using real-world data from the public healthcare system of Catalonia between 2012 and 2016. Propensity score matching was performed in patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), and DAA only (DAA) with concurrent controls. We estimated the annual incidence of overall cancer, hepatocellular carcinoma, and non-liver cancer of HCV-treated patients and their corresponding rate ratios. RESULTS: The study included 11,656 HCV-treated patients and 49,545 controls. We found statistically significant increases in the rate of overall cancer for IFN+DAA-treated (rate ratio [RR] 1.77, 95% confidence interval [CI] 1.27-2.46) and DAA-treated patients (RR 1.90, 95% CI 1.66-2.19) and in the rate of HCC for IFN-treated (RR 1.50, 95% CI 1.02-2.22), IFN+DAA-treated (RR 3.89, 95% CI 2.26-6.69), and DAA-treated patients (RR 6.45, 95% CI 4.90-8.49) compared with their corresponding controls. Moreover, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis (RR 1.92, 95% CI 1.51-2.44). CONCLUSIONS: Results showed that overall cancer and hepatocellular carcinoma incidence in Catalonia was significantly higher among HCV-treated patients compared with matched non-HCV-infected controls, and risks were higher in patients with cirrhosis. An increased awareness of the potential occurrence of uncommon malignant events and monitoring after HCV eradication therapy may benefit patients.

Direct-acting antivirals (DAAs) are effective drugs for eradicating hepatitis C virus (HCV). However, concerns about the risk of cancer after HCV eradication remain. Therefore, this study aimed to compare the incidence of cancer between patients treated with anti-HCV therapies in Catalonia (Spain) and properly matched, non-HCV-infected individuals (controls).This study was based on real-world data from the public healthcare system of Catalonia, specifically from patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), or DAA only (DAA). We calculated the incidence and rate ratios of overall cancer and hepatocellular carcinoma of HCV-treated patients.We observed that the rate of overall cancer increased in patients receiving DAA or IFN+DAA, whereas the rate of hepatocellular carcinoma increased in all groups of HCV-treated patients. Of note, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis. Thus, a close monitoring for detection of cancer in patients after HCV eradication seems reasonable, especially in those with cirrhosis.

Economic impact of inflammatory bowel disease in Catalonia: a population-based analysis.

Background: Inflammatory bowel disease (IBD) has a major economic impact on healthcare costs. Objectives: The aim of this study was to evaluate the current healthcare expenditure associated with IBD in a population-wide study in Catalonia. Design: Retrospective observational study. Methods: All patients with IBD included in the Catalan Health Surveillance System (CHSS) were considered eligible. The CHSS compiles data on more than 7 million individuals in 2020 (34,823 with IBD). Data on the use of healthcare resources and its economic impact were extracted applying the International Classification of Diseases, 10th revision, Clinical Modification codes (ICD-10-CM codes). Health expenditure, comorbidities, and hospitalization were calculated according to the standard costs of each service provided by the Department of Health of the Catalan government. The data on the IBD population were compared with non-IBD population adjusted for age, sex, and income level. IBD costs were recorded separately for Crohn's disease (CD) and ulcerative colitis (UC). Results: Prevalence of comorbidities was higher in patients with IBD than in those without. The risk of hospitalization was twice as high in the IBD population. The overall healthcare expenditure on IBD patients amounted to 164M€. The pharmacy cost represents the 60%. The average annual per capita expenditure on IBD patients was more than 3.4-fold higher (IBD 4200€, non-IBD 1200€). Average costs of UC were 3400€ and 5700€ for CD. Conclusion: The risk of comorbidities was twice as high in patients with IBD and their use of healthcare resources was also higher than that of their non-IBD counterparts. Per capita healthcare expenditure was approximately 3.4 times higher in the population with IBD. Trial registration: The study was not previously registered.

Economic impact of inflammatory bowel disease in Catalonia The manuscript includes data of the most recent epidemiologic data about the high economic impact of IBD in Catalonia.

The challenges of access to innovative medicines with limited evidence in the European Union.

The European Medicines Agency (EMA) fosters access to innovative medicines through accelerated procedures and flexibility in the authorization requirements for diseases with unmet medical needs, such as many rare diseases as well as oncological diseases. However, the resulting increase of medicines being marketed with conditional authorizations and in exceptional circumstances has lead to higher clinical uncertainty about their efficacy and safety than when the standard authorizations are applied. This uncertainty has significant implications for clinical practice and the negotiation of pricing and reimbursement, particularly as high prices are based on assumptions of high value, supported by regulatory prioritization. The burden of clinical development is often shifted towards public healthcare systems, resulting in increased spending budgets and opportunity costs. Effective management of uncertainty, through appropriate testing and evaluation, and fair reflection of costs and risks in prices, is crucial. However, it is important not to sacrifice essential elements of evidence-based healthcare for the sake of access to new treatments. Balancing sensitive and rational access to new treatments, ensuring their safety, efficacy, and affordability to healthcare systems requires thoughtful decision-making. Ultimately, a responsible approach to timely access to innovative medicines that balances the needs of patients with healthcare systems' concerns is necessary. This approach emphasizes the importance of evidence-based decision-making and fair pricing and reimbursement.

Utilisation of drugs for the treatment of psychiatric diseases in the pediatric population: focus on off-label use.

Psychotropics are increasingly used in pediatrics, often as off-label medicines. The guarantees of safety and efficacy are not always granted in clinical practice compared to adult authorised indications. A retrospective observational study was done to estimate the prevalence of psychotropic use in pediatric subjects of Catalonia (Spain). Anonymised data on dispensation of psychotropics to pediatric patients, demography and other related data were obtained by the local healthcare management for the period 2008-2017. Estimation of off-label use was done through description of drug dispensations with no authorised use related to age range. The prevalence of psychotropics was 40.8-64.2 per 1,000 pediatric inhabitants. Hydroxyzine-only represented two-thirds of dispensations, and when removed, the prevalence dropped to 26.4-32.2 per 1,000 pediatric inhabitants. Adolescents and boys were more likely to receive a psychotropic. Psychostimulants had the highest exposure rate, mainly due to methylphenidate. Off-label use was observed in 12% of subjects, corresponding to 4.6% of all dispensed psychotropics with boys being more exposed. The proportion of off-label use vs. labelled use was higher in younger populations. Aripiprazole had the highest off-label frequency. Our data support the frequent reality of off-label use in pediatrics, despite the potential underestimation related to the selected off-label definition. There is an urgent need to systematically ascertain effectiveness and any potential adverse events in the off-label pediatric setting, and to generate valuable information for risk-benefit assessment in these populations where extrapolation from adults is not reliable.