Use of electronic health data for the identification of cases and for the evaluation of healthcare consumptions and chronic kidney disease costs

Introduction Chronic kidney disease (CKD) is a common condition characterized by a gradual loss of kidney function and consequently increasing costs associated with the disease. Aims The aim was to use administrative databases and a pathology registry to characterize CKD patient according to their stage and to evaluate the burden of disease; to identify incident patients on dialysis; to investigate the impact of COVID-19 on mortality in CKD patients. Methods Data from a regional pathology registry and administrative databases were used to classify CKD patients into different disease progression subgroups (CT-PIRP classification) using the following 6 variables: age, sex, diabetes, glomerular filtration rate, proteinuria, phosphate level and different CKD stages (3a, 3b, 4, 5). Healthcare consumptions and costs were evaluated. Incident chronic dialysis patients were defined those seen regularly in outpatient clinics. The incidence and mortality of COVID-19 among CKD patients were estimated. Results The study cohort includes 7737 CKD patients, aged 73.2±11.6 years, 64.5% males, mostly stage 4 (3136, 40.5%) and 3b (2799, 36.2%). Average annual costs were significantly higher for CT-PIRP groups 2 and 3 (€7239 and €8825 respectively) and more than twofold higher for CKD stage 5 (€7,993) compared to stage 3a (€3,973). Both algorithms used to identify incident chronic dialysis patients had high sensitivity, 90.8% and 88.4%, high positive predictive value (84.0% and 82.0%) and high agreement (77.4% and 74.1%). The incidence of COVID-19 infection was 4.16%. COVID-19 hospitalized patients were the 95.5%, those on home isolation were the 3.6% and the 0.9% were asymptomatic. Compared to those without COVID-19, the overall excess mortality ranged between 34.4% and 56.3%. Conclusion Administrative databases are a powerful tool to describe the burden of CKD disease, in order to assess the interventions aimed at reducing the impact of CKD and improving the quality of care of CKD patients

Do coxibs reduce prescription of gastroprotective agents? Results of a record linkage study

BACKGROUND: Coxibs are claimed to be cost-effective drugs and reduced prescription of gastroprotective agents is assumed to be one of their major benefits. Real life prescription of these drugs may be substantially different than that considered in pharmacoeconomic analyses or claimed by drug companies, yet. Our objective was to evaluate whether coxibs were associated with reduced prescription of gastro-protective agents (GPAs, specifically proton pump inhibitors, H(2 )blockers and misoprostol) compared to non selective NSAIDs. METHODS: A record-linkage study was performed using 2001 outpatient prescription data from the province of Modena (about 632,000 inhabitants, in Northern Italy). Logistic regression was used to calculate the odds ratio of GPA prescription for coxib and non-selective NSAID adult users (> 14 years). Three categories of users were further investigated: "acute", "chronic and "incident or new". Main outcome measures were same-day co-prescription and 30 days prescription of GPAs in coxibs and non selective NSAIDs users. To limit selection bias, data were adjusted for age, sex, DDD of coxibs and non selective NSAIDs received during 2001, DDD of GPAs and (for non-incident users) DDD of NSAIDs received during the previous 4 years RESULTS: Same day co-prescription rates were similar considering the overall population and "acute" users. Chronic coxibs users instead showed higher co-prescription rates than chronic NSAIDs users (OR = 1.2, p < 0.05). GPA prescription within thirty days was also higher among all subgroups of coxibs users (OR ranging from 1.6 to 2.0, p < 0.001). CONCLUSION: Assumptions made in pharmacoeconomic analyses on coxibs (lower GPA prescription associated with coxibs use) may be overly optimistic. Claims made through cost-effectiveness data should be carefully interpreted, and mechanisms for attributing drug prices revised accordingly

Protective Effects of Home T2DM Treatment with Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Co-transporter-2 Inhibitors Against Intensive Care Unit Admission and Mortality in the Acute Phase of the COVID-19 Pandemic: A Retrospective Observational Study in Italy

Introduction: Type 2 diabetes mellitus (T2DM) is a relevant risk factor for severe forms of COVID-19 (SARS coronavrus 2 [SARS-CoV-2] disease 2019), and calls for caution because of the high prevalence of T2DM worldwide and the high mortality rates observed in patients with T2DM who are infected with SARS-CoV-2. People with T2DM often take dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1ras), or sodium-glucose co-transporter-2 inhibitors (SGLT-2is), all of which have clear anti-inflammatory effects. The study aimed to compare (i) the severity and duration of hospital stay between patients with T2DM categorized by pre-hospitalization drug class utilization and (ii) the COVID-19-related death rates of those three groups.Methods: We designed an observational, retrospective, multi-center, population-based study and extracted the hospital admission data from the health care records of 1916 T2DM patients over 18 years old who were previously on GLP-1ra, SGLT-2i, or DPP-4i monotherapy and were hospitalized for COVID-19 (diagnosis based on ICD.9/10 codes) between January 2020 and December 2021 in 14 hospitals throughout Italy. We analyzed general data, pre-admission treatment schedules, date of admission or transfer to the intensive care unit (ICU) (i.e., the index date; taken as a marker of increased COVID-19 disease severity), and death (if it had occurred). Statistics analyzed the impact of drug classes on in-hospital mortality using propensity score logistic regressions for (i) those admitted to intensive care and (ii) those not admitted to intensive care, with a random match procedure used to generate a 1:1 comparison without diabetes cohort replacement for each drug therapy group by applying the nearest neighbor method. After propensity score matching, we checked the balance achieved across selected variables if a balance was ever achieved. We then used propensity score matching between the three drug classes to assemble a sample in which each patient receiving an SGLT-2i was matched to one on a GLP-1ra, and each patient on a DPP-4i was matched to one on a GLP-1ra, adjusting for covariates. We finally used GLP-1ras as references in the logistic regression.Results: The overall mortality rate (MR) of the patients was 14.29%. The MR in patients with COVID was 53.62%, and it was as high as 42.42% in the case of associated T2DM, regardless of any glucose-lowering therapy. In those on DPP-4is, there was excess mortality; in those treated with GLP-1ras and SGLT-2is, the death rate was significantly lower, i.e., almost a quarter of the overall mortality observed in COVID-19 patients with T2DM. Indeed, the odds ratio (OR) in the logistic regression resulted in an extremely high risk of in-hospital death in individuals previously treated with DPP-4is [incidence rate (IR) 4.02, 95% confidence interval (CI) 2.2-5.7) and only a slight, nonsignificantly higher risk in those previously treated with SGLT-2is (IR 1.42, 95% CI 0.6-2.1) compared to those on GLP-1ras. Moreover, the longer the stay, the higher the death rate, which ranged from 22.3% for &lt;= 3-day stays to 40.3% for 4- to 14-day stays (p &lt; 0.01 vs. the former) and 77.4% for over-14-day stays (p &lt; 0.001 vs. both the others).Discussion: Our data do not support a protective role of DPP-4is; indeed, this role has already been questioned due to previous observations. However, the data do show a strong protective effect of SGLT-2is and GLP-1ras.Beyond lowering circulating glucose levels, those two drug classes were found to exert marked anti-phlogistic effects: SGLT-2is increased adiponectin and reduced urate, leptin, and insulin concentrations, thus positively affecting overall low-grade inflammation, and GLP-1ras may also greatly help at the lung tissue level, meaning that their extra-glycemic effects extend well beyond those acknowledged in the cardiovascular and renal fields.Conclusions: The aforedescribed observational clinical data relating to a population of Italian inpatients with T2DM suggest that GLP-1ras and SGLT-2is can be considered antidiabetic drugs of choice against COVID-19, and might even prove beneficial in the event of any upcoming pandemic that has life-threatening effects on the pulmonary and cardiovascular systems

Randomised controlled trials for evaluating the prescribing impact of information meetings led by pharmacists and of new information formats, in General Practice in Italy

<p>Abstract</p> <p>Background</p> <p>Suboptimal translation of valid and relevant information in clinical practice is a problem for all health systems. Lack of information independent from commercial influences, limited efforts to actively implement evidence-based information and its limited comprehensibility are important determinants of this gap and may influence an excessive variability in physicians' prescriptions. This is quite noticeable in Italy, where the philosophy and methods of Evidence-Based Medicine still enjoy limited diffusion among practitioners. Academic detailing and pharmacist outreach visits are interventions of proven efficacy to make independent and evidence-based information available to physicians; this approach and its feasibility have not yet been tested on a large scale and, moreover, they have never been formally tested in Italy.</p> <p>Methods/Design</p> <p>Two RCTs are planned:</p> <p>1) a two-arm cluster RCT, carried out in Emilia-Romagna and Friuli Venezia Giulia, will evaluate the effectiveness of small group meetings, randomising about 150 Primary Care Groups (corresponding to about 2000 GPs) to pharmacist outreach visits on two different topics. Physicians' prescriptions (expressed as DDD per 1000 inhabitants/day), knowledge and attitudes (evaluated through the answers to a specific questionnaire) will be compared for target drugs in the two groups (receiving/not receiving each topic).</p> <p>2) A three-arm RCT, carried out in Sardinia, will evaluate both the effectiveness of one-to-one meetings (one pharmacist visiting one physician per time) and of a 'new' information format (compared to information already available) on changing physicians' prescription of specific drugs. About 900 single GPs will be randomised into three groups: physicians receiving a visit supported by "traditional" information material, those receiving a visit with "new" information material on the same topic and those not receiving any visit/material.</p> <p>Discussion</p> <p>The two proposed RCTs aim to evaluate the organisational feasibility and barriers to the implementation of independent information programs led by NHS pharmacists. The objective to assess a 10 or 15% decreases in the prescription of the targeted drugs is quite ambitious in such 'natural' settings, which will be minimally altered by the interventions themselves; this in spite of the quite large sample sizes used comparing to other studies of these kind. Complex interventions like these are not easy to evaluate, given the many different variables into play. Anyway, the pragmatic nature of the two RCTs appears to be also one of their major strengths, helping to provide a deeper insight on what is possible to achieve – in terms of independent information – in a National Health System, with special reference to Italy.</p> <p>Trial registration</p> <p>ISRCTN05866587 (cluster RCT) and ISRCTN28525676 (single GPs RCT)</p

Dementia Improvement after Primary Hyperparathyroidism Surgery

This is the case of a 76-year-old man admitted to hospital in a delirium state, previously diagnosed with a major depressive disorder at an age of 50 years, treated for years for chronic tension headache. The computed tomography of the head resulted negative. Inpatient laboratory tests revealed a mild hypercalcemia. Due to the progression of the disease (delirium state, dementia, tension headache, and depression), he was again admitted to hospital. The patient showed dysarthria, postural tremors, mirror movements and palmar hyperhidrosis, mild ataxia when walking, and rigidity. Sleep disturbances were also observed. He underwent several clinical diagnostic tests, which resulted negative. After more than 2 years, the ultrasound of the neck identified enlarged parathyroid glands. The patient was surgically treated, and three parathyroid glands were removed. Parathyroidectomy and lithium treatment resulted in improvement of cognitive functions. In elderly patients, concomitant presence of cognitive dysfunction may mask the underlying primary hyperparathyroidism

Alfentanil and sufentanil in fast-track anesthesia for coronary artery bypass graft surgery.

Objective: To evaluate alfentanil, sufentanil, and the combination of both opioids in patients undergoing cardiac surgery. Design: Prospective, randomized study. Setting: University hospital. Participants: Patients undergoing coronary artery bypass graft (CABG) surgery (n 195), randomly assigned to 3 groups of 65 each. Interventions: Patients in group A received alfentanil, induction (15 g/kg) and maintenance (15 g/kg/hr); patients in group S received sufentanil, induction (1 g/kg) and maintenance (1 g/kg/h); and patients in group AS received alfentanil and sufentanil, induction with alfentanil (15 g/kg) and maintenance with sufentanil (1 g/ kg/hr). Measurements and Main Results: Hemodynamic data showed a reduction of all parameters at induction in the 3 groups (p &lt; 0.05). Cardiac index decreased at induction in all groups (p &lt; 0.05) but increased in groups S and AS toward baseline values at the end of surgery. The intubation time and length of stay in the intensive care unit were less in group AS (2.3 1.2 hours; p &lt; 0.001 and 20 8 hours; p &lt; 0.05), than in groups A (4.2 1.7 hours and 28 13 hours) and S (3.1 1.1 hours; p &lt; 0.05 and 26 12 hours). Length of hospital stay and patients’ outcome were similar in the 3 groups. Conclusion: Although the differences among groups regarding extubation time, intensive care unit length of stay, and some hemodynamic data were statistically significant, the differences were clinically small. All 3 anesthetic protocols were shown to be safe and appropriate for patients undergoing elective coronary artery bypass graft surgery and early postoperative tracheal extubation

One‐year mortality associated with COPD treatment: a comparison of tiotropium and long‐acting beta2‐agonists in three Italian regions: results from the OUTPUL study

Abstract Purpose Long‐acting bronchodilators, i.e. beta‐2‐agonists (LABA) and tiotropium are commonly used in COPD treatment. Choice of a specific agent is based on effectiveness and safety. Evidence yields controversial results with respect to mortality. The present study compared one‐year mortality associated to treatment with tiotropium versus LABA. Methods: A population‐based cohort study using data from Italian health information systems was performed. Patients aged 45+ years, discharged with COPD diagnosis in 2006–2009 were identified. Through record linkage with drug claims, patients who received a first prescription of LABA or tiotropium within 6 months after discharge were enrolled. The main analysis was restricted to naïve users (no prior use of either LABA or tiotropium). We used ‘intention to treat’ (ITT) and ‘as treated’ (AT) approaches. We followed patients for a maximum of 12 months. Hazard ratios (HRs) were calculated by Cox regression including quintiles of propensity score. In sensitivity analysis patients receiving tiotropium + LABA combination were included in the tiotropium group. Results: Among the 33 891 enrolees, 28% were exposed to Tio, 56% to LABA, 16% to both. Overall mean age was 74 years and the mortality rate was 122/1000 person‐years (py) at the ITT analysis and 108/1000 py at the AT analysis. The adjusted HR for tiotropium only compared with LABA only was 1.06 (95%CI: 0.94–1.20) at the ITT analysis and 1.00 (95%CI: 0.93–1.08) at the AT analysis. Results were robust in sensitivity analysis. Conclusions: In this real‐world study use of tiotropium was not associated with an increased risk of one‐year mortality compared with LABA. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd

Deaths related to pulmonary embolism and cardiovascular events before and during the 2020 COVID-19 pandemic: An epidemiological analysis of data from an Italian high-risk area

BACKGROUND: Pulmonary embolism is a known complication of coronavirus disease 2019 (COVID-19). Epidemiological population data focusing on pulmonary embolism-related mortality is limited. METHODS: Veneto is a region in Northern Italy counting 4,879,133 inhabitants in 2020. All ICD-10 codes from death certificates (1st January 2018 to 31st December 2020) were examined. Comparisons were made between 2020 (COVID-19 outbreak) and the average of the two-year period 2018-2019. All-cause, COVID-19-related and the following cardiovascular deaths have been studied: pulmonary embolism, hypertensive disease, ischemic heart disease, atrial fibrillation/flutter, and cerebrovascular diseases. RESULTS: In 2020, a total of 56,412 deaths were recorded, corresponding to a 16% (n = 7806) increase compared to the period 2018-2019. The relative percentage increase during the so-called first and second waves was 19% and 44%, respectively. Of 7806 excess deaths, COVID-19 codes were reported in 90% of death certificates. The percentage increase in pulmonary embolism-related deaths was 27% (95%CI 19-35%), 1018 deaths during the year 2020, compared to 804 mean annual deaths in the period 2018-2019. This was more evident among men, who experience an absolute increase of 147 deaths (+45%), than in women (+67 deaths; +14%). The increase was primarily driven by deaths recorded during the second wave (+91% in October-December). An excess of deaths, particularly among men and during the second wave, was also observed for other cardiovascular diseases, notably hypertensive disease, atrial fibrillation, cerebrovascular disease, and ischemic heart disease. CONCLUSIONS: We observed a considerable increase of all-cause mortality during the year 2020. This was mainly driven by COVID-19 and its complications. The relative increase in the number of pulmonary embolism-related deaths was more prominent during the second wave, suggesting a possible underdiagnosis during the first wave

Long Term Effectiveness on Prescribing of Two Multifaceted Educational Interventions: Results of Two Large Scale Randomized Cluster Trials

<div><p>Introduction</p><p>Information on benefits and risks of drugs is a key element affecting doctors’ prescribing decisions. Outreach visits promoting independent information have proved moderately effective in changing prescribing behaviours.</p><p>Objectives</p><p>Testing the short and long-term effectiveness on general practitioners’ prescribing of small groups meetings led by pharmacists.</p><p>Methods</p><p>Two cluster open randomised controlled trials (RCTs) were carried out in a large scale NHS setting. Ad hoc prepared evidence based material were used considering a therapeutic area approach - TEA, with information materials on osteoporosis or prostatic hyperplasia - and a single drug oriented approach - SIDRO, with information materials on me-too drugs of 2 different classes: barnidipine or prulifloxacin. In each study, all 115 Primary Care Groups in a Northern Italy area (2.2 million inhabitants, 1737 general practitioners) were randomised to educational small groups meetings, in which available evidence was provided together with drug utilization data and clinical scenarios. Main outcomes were changes in the six-months prescription of targeted drugs. Longer term results (24 and 48 months) were also evaluated.</p><p>Results</p><p>In the TEA trial, one of the four primary outcomes showed a reduction (prescription of alfuzosin compared to tamsulosin and terazosin in benign prostatic hyperplasia: prescribing ratio −8.5%, p = 0.03). Another primary outcome (prescription of risedronate) showed a reduction at 24 and 48 months (−7.6%, p = 0.02; and −9,8%, p = 0.03), but not at six months (−5.1%, p = 0.36). In the SIDRO trial both primary outcomes showed a statistically significant reduction (prescription of barnidipine −9.8%, p = 0.02; prescription of prulifloxacin −11.1%, p = 0.04), which persisted or increased over time.</p><p>Interpretation</p><p>These two cluster RCTs showed the large scale feasibility of a complex educational program in a NHS setting, and its potentially relevant long-term impact on prescribing habits, in particular when focusing on a single drug. National Health systems should invest in independent drug information programs.</p><p>Trial Registration</p><p>Controlled-Trials.com <a href="http://www.controlled-trials.com/ISRCTN05866587" target="_blank">ISRCTN05866587</a></p></div