BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).
BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650â¯mL as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.
BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV), consisting of varicella-zoster virus glycoprotein E (gE) and the AS01B adjuvant system, effectively prevents herpes zoster (HZ). In the absence of a well-defined correlate of protection, it is important to monitor the RZV immune response, as a proxy of clinical effectiveness. METHODS: This systematic review examined post-vaccination parameters: humoral and cell-mediated immunity, avidity index, geometric mean concentration of antibody (GMC), and immunity persistence. The meta-analysis used a random-effects model, and subgroup and meta-regression analyses were conducted. RESULTS: Among 37 included articles, after one month from RZV-dose 2, the pooled response rate for anti-gE humoral immunity was 95.2% (95%CI 91.9-97.2), dropping to 77.6% (95%CI 64.7-86.8) during immunosuppression. The anti-gE cell-mediated immunity-specific response reached 84.6% (95%CI 75.2-90.9). Varying factors, such as age, sex, coadministration with other vaccines, prior HZ, or live-attenuated zoster vaccine, did not significantly affect response rates. RZV induced a substantial increase in gE avidity. Immunity persistence was confirmed, with more rapid waning in the very elderly. CONCLUSIONS: This systematic review indicates that RZV elicits robust immunogenicity and overcomes immunocompromising conditions. The findings underscore the need for further research, particularly on long-term immunity, and have the potential to support HZ vaccination policies and programs.
OBJECTIVES: To estimate the incidence and prevalence of SLE in Italy, and to describe the demographic and clinical characteristics of patients with newly diagnosed SLE. METHODS: A retrospective cohort study was conducted using The Health Improvement Network general practice database in Italy, encompassing data from 634 753 people. SLE cases were identified over the period 2017-2022, employing three alternative definitions to provide a more detailed understanding of SLE characteristics. Incidence rates were expressed as cases per 100 000 person-years and prevalence as cases per 100 000 people. Demographic and clinical characteristics of incident SLE cases were also studied. RESULTS: From 2017 to 2022, a total of 191 incident and 1385 prevalent cases were identified under our first definition. In 2022, the incidence rate was 6.51 cases (95% CI 6.29 to 6.74) per 100 000 person-years, and the prevalence 60.57 (95% CI 59.89 to 61.25) per 100 000 people, being the prevalence five times higher in women compared with men. Both estimates have trended upwards since 2017. A geographical variation across the country was also seen. The demographic and clinical characteristics of incident SLE cases were described, while the potential associations of SLE incidence with some pre-existing conditions were observed, such as chronic kidney disease, chronic hepatic disease, rheumatoid arthritis and Sjogren's syndrome. CONCLUSIONS: The results of this nationwide study, the first conducted in Italy, showed that the incidence of SLE has increased in Italy in recent years. Age, sex, and area of residence strongly correlate with the epidemiology of this condition.
Databases, Factual , Lupus Erythematosus, Systemic , Primary Health Care , Humans , Italy/epidemiology , Male , Female , Retrospective Studies , Adult , Middle Aged , Lupus Erythematosus, Systemic/epidemiology , Incidence , Prevalence , Primary Health Care/statistics & numerical data , Aged , Young Adult , Adolescent
AIM: In 2022, in Italy, general practitioners (GPs) have been allowed to prescribe SGLT2i in Type 2 Diabetes (T2D) under National Health Service (NHS) reimbursement. In the pivotal clinical trial named DECLARE-TIMI 58, dapagliflozin reduced the risk of hospitalization for heart failure, CV death and kidney disease progression compared to placebo in a population of T2D patients. This study evaluated the health and economic impact of dapagliflozin for T2D patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian GPs setting. METHODS: A budget impact model was developed to assess the health and economic impact of introducing dapagliflozin in GPs setting. The analysis was conducted by adopting the Italian NHS perspective and a 3-year time horizon. The model estimated and compared the health outcomes and direct medical costs associated with a scenario with dapagliflozin and other antidiabetic therapies available for GPs prescription (scenario B) and a scenario where only other antidiabetic therapies are available (scenario A). Rates of occurrence of cardiovascular and renal complications as well as adverse events were captured from DECLARE-TIMI 58 trial and the literature, while cost data were retrieved from the Italian tariff and the literature. One-way sensitivity analyses were conducted to test the impact of model parameters on the budget impact. RESULTS: The model estimated around 442.000 patients eligible for the treatment with dapagliflozin in the GPs setting for each simulated year. The scenario B compared to scenario A was associated with a reduction in the occurrence of cardiovascular and renal complication (-1.83%) over the 3 years simulated. Furthermore, the scenario A allowed for an overall cost saving of 102,692,305: 14,521,464 in the first year, 33,007,064 in the second and 55,163,777 in the third. The cost of cost of drug acquisition, the probability of cardiovascular events and the percentage of patients potentially eligible to the treatment were the factor with largest impact on the results. CONCLUSIONS: The use of dapagliflozin in GPs setting reduce the number of CVD events, kidney disease progression and healthcare costs in Italy. These data should be considered to optimize the value produced for the T2D patients who had or were at risk for atherosclerotic cardiovascular disease.
BACKGROUND: Alongside health consequences, cesarean delivery (CD) has been associated with increased healthcare resource utilization (HCRU). A CD should be performed in case of placenta previa; in turn, the most appropriate mode of birth in women with a low-lying placenta (LLP) is still controversial. Since no previous data are available on the topic, the aim of this study was to evaluate the HCRU and economic impact on the Italian HC system of vaginal birth (VB) and CD in women with a LLP. METHODS: This retrospective study used patient-level real-world data of a cohort of women with a LLP confirmed at 28-30 weeks. A cost-minimization analysis (CMA) was conducted to compare VB and CD. Since Diagnosis-Related-Group payment may not reflect the actual use of hospital resources, a micro-costing analysis (MCA) was performed to more comprehensively evaluate the economic impact of VB and CD. RESULTS: The study included 86 women with a LLP at the third trimester scan, of which 49 (57%) had a VB and 37 (43%) underwent a CD. The CMA showed an economically marginal difference between VB and CD, especially when considering opportunity costs associated with the resources needed to look after women. However, the MCA identified charges for each VB being about half of those for each CD. CONCLUSIONS: The use of patient-level real-world data allowed to generate basic information to assess the value of available interventions in case of LLP. A VB should be promoted in women with LLP, avoiding further burden on the HC system's limited resources.
BACKGROUND: Vaccination plays a critical role in mitigating the burden associated with yellow fever (YF). However, there is a lack of comprehensive evidence on the humoral response to primary vaccination in the paediatric population, with several questions debated, including the response when the vaccine is administered at early ages, the effect of co-administration with other vaccines, the duration of immunity and the use of fractional doses, among others. This study summarizes the existing evidence regarding the humoral response to primary YF vaccination in infants and children. METHODS: Studies on the humoral response to primary YF vaccination in children aged 12 years or younger were reviewed. The humoral vaccine response rate (VRR), i.e. the proportion of children who tested positive for vaccine-induced YF-specific neutralizing antibodies, was pooled through random-effects meta-analysis and categorized based on the time elapsed since vaccination. Subgroup, meta-regression and sensitivity analyses were performed. RESULTS: A total of 33 articles met the inclusion criteria, with all but one conducted in countries where YF is endemic. A total of 14 028 infants and children entered this systematic review. Within three months following vaccination, the pooled VRR was 91.9% (95% CI 89.8-93.9). A lower VRR was observed with the 17DD vaccine at the meta-regression analysis. No significant differences in immunogenicity outcomes were observed based on age, administration route, co-administration with other vaccines, or fractional dosing. Results also indicate a decline in VRR over time. CONCLUSIONS: Primary YF vaccination effectively provides humoral immunity in paediatric population. However, humoral response declines over time, and this decline is observable after the first 18 months following vaccination. A differential response according to the vaccine substrain was also observed. This research has valuable implications for stimulating further research on the primary YF vaccination in infants and children, as well as for informing future policies.
Yellow Fever Vaccine , Yellow Fever , Child , Infant , Humans , Yellow Fever/prevention & control , Antibodies, Neutralizing , Vaccination/methods , Immunity, Humoral , Antibodies, Viral
INTRODUCTION: Considering the advances in haemophilia management and treatment observed in the last decades, a new set of value-based outcome indicators is needed to assess the quality of care and the impact of these medical innovations. AIM: The Value-Based Healthcare in Haemophilia project aimed to define a set of clinical outcome indicators (COIs) and patient-reported outcome indicators (PROIs) to assess quality of care in haemophilia in high-income countries with a value-based approach to inform and guide the decision-making process. METHODS: A Value-based healthcare approach based on the available literature, current guidelines and the involvement of a multidisciplinary group of experts was applied to generate a set of indicators to assess the quality of care of haemophilia. RESULTS: A final list of three COIs and five PROIs was created and validated. The identified COIs focus on two domains: musculoskeletal health and function, and safety. The identified PROIs cover five domains: bleeding frequency, pain, mobility and physical activities, Health-Related Quality of Life and satisfaction. Finally, two composite outcomes, one based on COIs, and one based on PROIs, were proposed as synthetic outcome indicators of quality of care. CONCLUSION: The presented standard set of health outcome indicators provides the basis for harmonised longitudinal and cross-sectional monitoring and comparison. The implementation of this value-based approach would enable a more robust assessment of quality of care in haemophilia, within a framework of continuous treatment improvements with potential added value for patients. Moreover, proposed COIs and PROIs should be reviewed and updated routinely.
Hemophilia A , Humans , Hemophilia A/drug therapy , Quality of Life , Cross-Sectional Studies , Value-Based Health Care , Outcome Assessment, Health Care
OBJECTIVES: The authors report their experience of a protocol for deep sedation with ketamine in spontaneous respiration during the pulsed-field ablation (PFA) of atrial fibrillation (AF). DESIGN: Observational, prospective, nonrandomized fashion. SETTING: Single-center hospitalized patients. PARTICIPANTS: All consecutive patients undergoing PFA of AF. INTERVENTIONS: Patients undergoing deep sedation with intravenous ketamine. MEASUREMENTS AND MAIN RESULTS: The authors' sedation protocol involves the intravenous administration of fentanyl (1.5 µg/kg) and midazolam (2 mg) at low doses before local anesthesia with lidocaine. A ketamine adjunct (1 mg/kg) in 5-minute boluses was injected about 5 minutes before the first PFA delivery. The authors enrolled 117 patients (age = 59 ± 10 y, 74.4% males, body mass index = 27.6 ± 5 kg/m2, fluoroscopy time = 24 ± 14 minutes, skin-to-skin time = 80 ± 40 minutes and PFA LA dwell time = 24 ± 7 minutes). By the end of the procedure, pulmonary vein isolation had been achieved in all patients using PFA alone. The mean time under sedation was 54.9 ± 6 minutes, with 92 patients (79%) being sedated for <1 hour. A satisfactory Ramsay Sedation Scale level before ketamine administration was achieved in all patients, except one (80.3% of the patients with rank 3; 18.4% with rank 2). In all procedures, the satisfaction level was found acceptable by both the patient and the primary operator (satisfactory in 98.2% of cases). All patients achieved a Numeric Rating Scale for Pain ≤3 (none or mild). No major procedure or anesthesia-related complications were reported. CONCLUSION: The authors' standardized sedation protocol with the administration of drugs with rapid onset and pharmacologic offset at low doses was safe and effective, with an optimal degree of patient and operator satisfaction.
Atrial Fibrillation , Deep Sedation , Ketamine , Propofol , Male , Humans , Middle Aged , Aged , Female , Prospective Studies , Administration, Intravenous , Anesthesia, Local , Atrial Fibrillation/surgery , Respiration
BACKGROUD: A huge amount of data about psychosocial issues of people with haemophilia (PwH) are available; however, these materials are fragmentary and largely outdated, failing to reflect the impact of current treatment strategies. AIM: Describing the influence of illness on psychosocial aspects of adult PwH (≥18 years) and caregivers of children with haemophilia (CPwH) without inhibitors, in Italy. METHODS: Surveys (for adult PwH, CPwH and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. RESULTS: A total of 120 PwH without inhibitors and 79 CPwH completed the survey. Adult patients reported a significant impairment in many psychosocial aspects, including working activities, relations with family members and social relations. Caregivers generally reported better scores in all aspects of the survey. Mobility, Pain and Mental health domains of EQ-5D were the most frequently impaired in both patients and caregivers, reducing the perceived quality of life. Genetic counselling was an important issue, 53% of CPwH declaring unawareness of their carrier status, as well as the psychological support offered by the reference center, 67.0% of respondents reporting that no psychological support was provided at the time of diagnosis communication. CONCLUSION: This study provides information about PwH's and CPwH's point of view in the current scenario of continuous innovations in haemophilia treatment and management furthermore, updated insights on psychosocial problems faced by patients and caregivers are reported.
Hemophilia A , Adult , Child , Humans , Hemophilia A/therapy , Quality of Life , Caregivers/psychology , Surveys and Questionnaires , Italy
BACKGROUND AND PURPOSE: Essential tremor (ET) is one of the most common neurological disorders, but information on treatment pattern is still scant. The aim of this study was to describe the demographic and clinical characteristics, treatment patterns, and determinants of drug use in patients with newly diagnosed ET in France and the United Kingdom. METHODS: Incident cases of ET diagnosed between January 1, 2015 and December 31, 2018 with 2 years of follow-up were identified by using The Health Improvement Network (THIN®) general practice database. During the follow-up, we assessed the daily prevalence of use and potential switches from first-line to second-line treatment or other lines of treatment. Logistic regression models were conducted to assess the effect of demographic and clinical characteristics on the likelihood of receiving ET treatment. RESULTS: A total of 2957 and 3249 patients were selected in the United Kingdom and France, respectively. Among ET patients, drug use increased from 12 months to 1 month prior the date of index diagnosis (ID). After ID, nearly 40% of patients received at least one ET treatment, but during follow-up drug use decreased and at the end of the follow-up approximately 20% of patients were still on treatment. Among treated patients, ≤10% maintained the same treatment throughout the entire follow-up, nearly 20% switched, and 40%-75% interrupted any treatment. Results from the multivariate analysis revealed that, both in France and the United Kingdom, patients receiving multiple concomitant therapies and affected by psychiatric conditions were more likely to receive an ET medication. CONCLUSION: This study shows that ET is an undertreated disease with a lower-than-expected number of patients receiving and maintaining pharmacological treatment. Misclassification of ET diagnosis should be acknowledged; thus, results require cautious interpretation.
Essential Tremor , Humans , Essential Tremor/diagnosis , Essential Tremor/drug therapy , Essential Tremor/epidemiology , Primary Health Care , United Kingdom/epidemiology , France/epidemiology , Retrospective Studies
In elderly patients undergoing cardiac surgery, extracorporeal circulation affects the incidence of post-operative delirium and cognitive impairment with an impact on quality of life and mortality. In this study, a new oxygenator system (RemoweLL 2) was tested against a conventional system to assess its efficacy in reducing the onset of postoperative delirium and cognitive dysfunction and the levels of serum inflammatory markers. A total of 154 patients (>65 y.o.) undergoing cardiopulmonary bypass (CPB) were enrolled and randomly assigned to oxygenator RemoweLL 2 (n = 81) or to gold standard device Inspire (n = 73) between September 2019 and March 2022. The aims of the study were to assess the incidence of delirium and the cognitive decline by neuropsychiatric tests and the MoCa test intra-hospital and at 6 months after CPB. Inflammation biomarkers in both groups were also evaluated. Before the CPB, the experimental groups were comparable for all variables. After CPB, the incidence of severe post-operative delirium showed a better trend (p = 0.093) in patients assigned to RemoweLL 2 (16.0%) versus Inspire (26.0%). Differences in enolase levels (p = 0.049), white blood cells (p = 0.006), and neutrophils (p = 0.003) in favor of RemoweLL 2 were also found. The use of novel and better construction technologies in CPB oxygenator devices results in measurable better neurocognitive and neurological outcomes in the elderly population undergoing CPB.
Seasonal variation in influenza vaccine effectiveness (VE) makes real-world evidence (RWE) useful in supplementing the clinical-evidence base from randomized clinical trials. Adjuvanted inactivated influenza vaccine (aIIV) VE has been evaluated in multiple nonrandomized RWE studies. A systematic literature review of RWE studies evaluating the absolute or relative VE of aIIV was conducted. Identified studies were assessed by evaluators for risk of bias (RoB) by means of the ROBINS-I (Reduction of Bias In Non-randomized Studies of Interventions) tool to inform evidence-based medicine deliberations. Differences in evaluator assessments were resolved by consensus. The literature review yielded 14 follow-up studies, seven test-negative case-control (TNCC) studies, five traditional case-control studies, and one cluster-randomized clinical trial. Most follow-up studies and three TNCC studies were judged at low RoB. Issues increasing RoB included inadequate control of confounding, selection of controls, and reliance on recall of vaccination. The concerns identified in any of the designs could be mitigated with straightforward revisions to design or implementation. 17 of 27 nonrandomized studies of adjuvanted influenza-vaccine effectiveness, some from each of four study designs, were judged at low risk of material bias. These studies merit credence in assessing aIIV effectiveness relative to other influenza vaccines.
Influenza Vaccines , Influenza, Human , Humans , Adjuvants, Immunologic , Bias , Case-Control Studies , Vaccines, Inactivated , Randomized Controlled Trials as Topic
INTRODUCTION: Clinical trials confirmed the beneficial effects of adding pertuzumab (P) to the combination of trastuzumab-chemotherapy (TC) in the (neo)adjuvant setting of high-risk HER2-positive early breast cancer (HER2+BC). We evaluated the clinical, economic and societal impact of adding pertuzumab to neoadjuvant TC combination (TPC) in Italy. METHODS: A cost-consequence analysis comparing TPC vs. TC was performed developing a cohort-based multi-state Markov model to estimate the clinical, societal and economic impact of the neoadjuvant therapy of TPC versus TC in HER2+BC at high-risk of recurrence. The model works on a cycle length of 1 month and 5-years-time horizon. Literature review-based data were used to populate the model. The following clinical and economic outcomes were estimated: cumulative incidence of loco-regional/distant recurrences, life of years and QALY and both direct and indirect costs (). Finally, sensitivity analyses were performed. RESULTS: TPC was associated with a 75,630 saved of direct costs. Specifically, it was associated with an initial increase of treatment costs (+4.8%) followed by reduction of recurrence management cost (-20.4%). TPC was also associated with an indirect cost reduction of 1.40%, as well as decreased incidence of distant recurrence (-20.14%), days of work lost (-1.53%) and days lived with disability (-0.50%). Furthermore, TPC reported 10,47 QALY gained (+2.77%) compared to TC. The probability to achieve the pathological complete response (pCR) was the parameter that mostly affected the results in the sensitivity analysis. CONCLUSION: Our findings suggested that TPC combination could be a cost-saving option in patients with HER2+BC at high-risk of recurrence.
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Neoadjuvant Therapy/methods , Receptor, ErbB-2/analysis , Trastuzumab/therapeutic use , Italy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
AIMS: A standardized sedation protocol for pulsed-field ablation (PFA) of atrial fibrillation (AF) through irreversible cellular electroporation has not been well established. We report our experience of a protocol for deep sedation with ketamine in spontaneous respiration during the PFA of AF. METHODS AND RESULTS: All consecutive patients undergoing PFA for AF at our center were included. Our sedation protocol involves the intravenous administration of fentanyl (1.5â mcg/kg) and midazolam (2â mg) at low doses before local anesthesia with lidocaine. A ketamine adjunct (1â mg/kg) was injected about 5 minutes before the first PFA delivery. We enrolled 66 patients (age = 59 ± 9 years, 78.8% males, body mass index = 28.8 ± 5â kg/m2, fluoroscopy time = 21[15-30]â min, skin-to-skin time = 75[60-100]â min and PFA LA dwell time = 25[22-28]â min). By the end of the procedure, PVI had been achieved in all patients by means of PFA alone. The mean time under sedation was 56.4 ± 6â min, with 50 (76%) patients being sedated for less than 1 hour. A satisfactory Ramsey Sedation Scale level before ketamine infusion was achieved in all patients except one (78.8% of the patients with rank 3; 19.7% with rank 2). In all procedures, the satisfaction level was found to be acceptable by both the patient and the primary operator (Score = 0 in 98.5% of cases). All patients reported none or mild pain. No major procedure or anesthesia-related complications were reported. CONCLUSION: Our standardized sedation protocol with the administration of drugs with rapid onset and pharmacological offset at low doses was safe and effective, with an optimal degree of patient and operator satisfaction. CLINICAL TRIAL REGISTRATION: Advanced TecHnologies For SuccEssful AblatioN of AF in Clinical Practice (ATHENA). URL: http://clinicaltrials.gov/Identifier: NCT05617456.
Anesthesia , Atrial Fibrillation , Catheter Ablation , Deep Sedation , Ketamine , Aged , Female , Humans , Male , Middle Aged , Administration, Intravenous , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Catheter Ablation/methods , Deep Sedation/adverse effects , Deep Sedation/methods , Ketamine/adverse effects , Respiration , Treatment Outcome
The management of atrial fibrillation (AF), the most common sustained arrhythmia, impacts healthcare resource utilization (HCRU). This study aims to estimate global resource use in AF patients, using the GARFIELD-AF registry. A prospective cohort study was conducted to characterize HCRU in AF patients enrolled in sequential cohorts from 2012 to 2016 in 35 countries. Components of HCRU studied were hospital admissions, outpatient care visits, and diagnostic and interventional procedures occurring during follow-up. AF-related HCRU was reported as the percentage of patients demonstrating at least one event and was quantified as rate-per-patient-per-year (PPPY) over time. A total of 49,574 patients was analyzed, having an overall median follow-up of 719 days. Almost all patients (99.5%) had at least one outpatient care visit, while hospital admissions were the second most frequent medical contact, with similar proportions in North America (37.5%) and Europe (37.2%), and slightly higher in the other GARFIELD-AF countries (42.0%; namely Australia, Egypt, and South Africa). Asia and Latin America showed lower percentages of hospitalizations, outpatient care visits, and diagnostic and interventional procedures. Analyses of GARFIELD-AF highlighted the vast AF-related HCRU, underlying significant geographical differences in the type, quantity, and frequency of AF-related HCRU. These differences were likely attributable to health service availability and differing models of care.
There are many consequences of heart failure (HF), including symptoms, impaired health-related quality of life (HRQoL), and physical and social limitations (functional status). These have a substantial impact on patients' lives, yet are not routinely captured in clinical trials. Patient-reported outcomes (PROs) can quantify patients' experiences of their disease and its treatment. Steps can be taken to improve the use of PROs in HF trials, in regulatory and payer decisions, and in patient care. Importantly, PRO measures (PROMs) must be developed with involvement of patients, family members, and caregivers from diverse demographic groups and communities. PRO data collection should become more routine not only in clinical trials but also in clinical practice. This may be facilitated by the use of digital tools and interdisciplinary patient advocacy efforts. There is a need for standardization, not only of the PROM instruments, but also in procedures for analysis, interpretation and reporting PRO data. More work needs to be done to determine the degree of change that is important to patients and that is associated with increased risks of clinical events. This 'minimal clinically important difference' requires further research to determine thresholds for different PROMs, to assess consistency across trial populations, and to define standards for improvement that warrant regulatory and reimbursement approvals. PROs are a vital part of patient care and drug development, and more work should be done to ensure that these measures are both reflective of the patient experience and that they are more widely employed.
Heart Failure , Quality of Life , Humans , Heart Failure/therapy , Patient Participation , Patient Reported Outcome Measures , Caregivers
BACKGROUND: Recent developments improved outcomes in patients with autoimmune diseases. Biologics were approved as first-line treatment in selected naïve patients with plaque psoriasis (PsO), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). Among them, secukinumab was most recently approved for treatment of active nr-axSpA in adults. In this work, we assessed the budget impact of new secukinumab treatment options in the Italian market. METHODS: A cross-indication budget impact model was designed to estimate the effects of adding secukinumab in the Italian market from the National Health System perspective over a 3-year period. The model included all adults with PsO, PsA, AS and nr-axSpA, treated with biologics or biosimilars. It compared costs between two scenarios, secukinumab availability or absence, for the four diseases combined and taken individually. A sensitivity analyses was conducted. RESULTS: There were 68,121 adult patients treated with biologics in 2021 and 68,341 in 2023. The budget impact analysis (BIA) on all indications showed a cost reduction of 33.7 million (- 1.5%) over 3 years with the introduction of secukinumab. PsA patients had the highest saving (- 34.9 million), followed by PsO patients (- 7.8 million). Cost saving in PsO patients was balanced by increased budget reported in AS patients (+ 8.0 million). In nr-axSpA patients, secukinumab reported no significant budget increase (+ 1.0%). CONCLUSION: This BIA accounted for the new indication of secukinumab in nr-axSpA patients, reporting no significant changes in the required budget and adding an effective treatment option. Considering all indications, secukinumab is a sustainable treatment option.
BACKGROUND: This study was aimed at estimating the appropriate price of tucatinib plus trastuzumab and capecitabine (TXC), as third-line treatment, in HER2+ breast cancer (BC) patients from the Italian National Health System (NHS) perspective. METHODS: A partitioned survival model with three mutually exclusive health states (i.e., progression-free survival (PFS), progressive disease (PD), and death) was used to estimate the price of tucatinib vs trastuzumab emtansine (TDM-1), considering a willingness to pay (WTP) of 60,000 EUR. Data from the HER2CLIMB trial, the Italian population, and the literature were used as input. The model also estimated the total costs and the life-years (LY) of TXC and TDM1. Deterministic and probabilistic (PSA) sensitivity analyses were conducted to evaluate the robustness of the model. RESULTS: In the base case scenario, the appropriate price of tucatinib was 4828.44 EUR per cycle. The TXC resulted in +0.28 LYs and +16,628 EUR compared with TDM-1. Results were mainly sensitive to therapy intensity variation. In PSA analysis, TXC resulted cost-effective in 53% of the simulations. Assuming a WTP ranging 20,000-80,000 EUR, the tucatinib price ranged from 4090.60 to 5197.41 EUR. CONCLUSIONS: This study estimated the appropriate price for tucatinib according to different WTP in order to help healthcare decision makers to better understand the treatment value.
