The psychosocial impact of haemophilia from patients' and caregivers' point of view: The results of an Italian survey.

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issues of people with haemophilia (PwH) are available; however, these materials are fragmentary and largely outdated, failing to reflect the impact of current treatment strategies.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.

Healthcare Resource Utilization in Patients with Newly Diagnosed Atrial Fibrillation: A Global Analysis from the GARFIELD-AF Registry.

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.

Personalized Prophylaxis with myPKFiTCE: A Real-World Cost-Effectiveness Analysis in Haemophilia A Patients.

Background and Objectives: This study aimed to assess the effectiveness and costs associated with pharmacokinetics-driven (PK) prophylaxis based on the myPKFiT® device in patients affected by hemophilia A (HA) in Italy. Materials and Methods: An observational retrospective study was conducted in three Italian hemophilia centers. All patients with moderate or severe HA, aged ≥ 18 years, capable of having PK estimated using the myPKFiT device, and who had had a clinical visit between 1 November 2019 and 31 March 2022 were included. Differences in clinical, treatment, health resources, and cost data were assessed comparing post-PK prophylaxis with pre-PK. The incremental cost-effectiveness ratio (ICER) was estimated as cost (EUR) per bleed avoided. Results: The study enrolled 13 patients with HA. The mean annual bleeding rate decreased by -1.45 (-63.80%, p = 0.0055) after the use of myPKFiT®. Overall, the consumption of FVIII IU increased by 1.73% during follow-up compared to the period prior the use of the myPKFiT. Prophylaxis based on the myPKFiT resulted in an ICER of EUR 5099.89 per bleed avoided. Conclusions: The results of our study support the idea that the use of PK data in clinical practice can be associated with an improvement in the management of patients, as well as clinical outcomes, with a reasonable increase in costs.

Multiple Sclerosis Progressive Courses: A Clinical Cohort Long-Term Disability Progression Study.

OBJECTIVES: Improving the understanding of multiple sclerosis (MS) mechanism and disability progression over time is essential to assess the value of healthcare interventions. Poor or no data on disability progression are available for progressive courses. This study aims to fill this gap. METHODS: An observational cohort study of patients with primary MS (PPMS) and secondary progressive MS (SPMS) was conducted on 2 Italian MS centers disease registries over an observational time of 34 years. Annual transition probabilities among Expanded Disability Status Scale (EDSS) states were estimated using continuous Markov models. A sensitivity analysis was performed in relation to clinical characteristic associated to disability progression. RESULTS: The study cohort included 758 patients (274 PPMS and 434 SPMS) with a median follow-up of 8.2 years. Annual transition probability matrices of SPMS and PPMS reported different annual probabilities to move within EDSS levels. Excluding EDSS associated to relapse events or patient with relapses, the annual probability of staying stable in an EDSS level increased in both disease courses even not significantly. CONCLUSIONS: This study provides estimates of annual disability progression as EDSS changes for PPMS and SPMS. These estimates could be a useful tool for healthcare decision makers and clinicians to properly assess impact of clinical interventions.

Haemophilia management and treatment: An Italian survey on patients', caregivers' and clinicians' point of view.

INTRODUCTION: Haemophilia management and patients' quality of life significantly improved. However, data on current patients', caregivers' and clinicians' satisfaction and limitations of treatments and haemophilia management are limited. AIM: Assessing the management satisfaction and unmet needs from the perspective of Italian patients with haemophilia (PWH) without inhibitors (or caregivers if children) and of specialist physicians. METHODS: Surveys (for patients≥18 years, caregivers of children and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. RESULTS: Among 275 participants, 120 (43.6%) were PWH without inhibitors, 79 (28.7%) caregivers and 37 (13.4%) clinicians. Patients and caregivers perceived a higher control of the disease compared to clinicians. However, more than 40% of patients and caregivers reported to feel significantly conditioned by the risk of bleeding during their daily life. PWH reported a 6-month mean/median (range) of bleeds 2.3/.0 (0-24) and caregivers 1.3/.0 (0-16) in children. The treatment burden (frequency of administration) was not satisfactory for more than half adults and caregivers of children treated with prophylaxis. A good access to treatment, haemophilia centres and medical service was reported, with issues associated to the multidisciplinary approach and treatment at emergency department. CONCLUSIONS: This large national study provides an updated overview of haemophilia care in Italy from different points of views, highlighting positive aspects and unmet needs. This information can guide future interventions to improve haemophilia management and the assessment of impact of new treatment options.

Occupational Exposure in the Lombardy Region (Italy) to SARS-CoV-2 Infection: Results from the MUSTANG-OCCUPATION-COVID-19 Study.

Sero-epidemiological surveys are valuable attempts to estimate the circulation of SARS-CoV-2 in general or selected populations. Within this context, a prospective observational study was conducted to estimate the prevalence and persistence of SARS-CoV-2 antibodies in different categories of workers and factors associated with positivity, through the detection of virus-specific immunoglobulin G and M (IgG/IgM) in serum samples. Enrollees were divided in low exposure and medium-high groups on the basis of their work activity. Antibody responders were re-contacted after 3 months for the follow-up. Of 2255 sampled workers, 4.8% tested positive for SARS-CoV-2 IgG/IgM antibodies, with 81.7% to IgG only. Workers who continued to go to their place of work, were healthcare workers, or experienced at least one COVID-19-related symptom were more likely to test positive for SARS-CoV-2 antibodies. SARS-CoV-2 antibodies prevalence was significantly higher in the medium-high risk vs. low-risk group (7.2% vs. 3.0%, p < 0.0001). At 3-month follow-up, 81.3% of subjects still had antibody response. This study provided important information of SARS-CoV-2 infection prevalence among workers in northern Italy, where the impact of COVID-19 was particularly intense. The presented surveillance data give a contribution to refine current estimates of the disease burden expected from the SARS-CoV-2.

Cost-Effectiveness Analysis of Cannabinoid Oromucosal Spray Use for the Management of Spasticity in Subjects with Multiple Sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a highly symptomatic disease, with a wide range of disabilities affecting many bodily functions, even in younger persons with a short disease history. The availability of a cannabinoid oromucosal spray (Sativex) for the management of treatment-resistant MS spasticity has provided a new opportunity for many patients. OBJECTIVE: Our study aimed to assess the cost effectiveness of Sativex in Italian patients with treatment-resistant MS spasticity. The analysis was based on the real-world data of a large registry of Italian patients. METHODS: A cost-utility analysis was conducted using data collected prospectively from an electronic registry of all patients who began to use Sativex for MS-resistant spasticity between January 2014 and February 2015 in 30 specialized MS units across Italy and were followed up for ≤ 6 months. Data on drug consumption and spasticity/utility were used to estimate the incremental cost-effectiveness ratio (ICER) of Sativex, as compared with no intervention. No costs or spasticity/utility changes were assumed for no treatment intervention. The ICER was expressed as quality-adjusted life-years (QALYs) gained, using the Italian NHS perspective and a 6-month time horizon. RESULTS: Sativex effectiveness and consumption was estimated analyzing data of 1350 patients from the registry. These patients reported a mean (SD) utility increment of 0.087 (0.069) after 1 month of treatment, 0.118 (0.073) after 3 months' treatment and 0.127 (0.080) after 6 months' treatment. The 6-month cost of treating the entire population with Sativex was €1,361,266, with a €1008 cost and 0.0284 QALYs gained per patient. The estimated ICER was €35,516 per QALY gained, with little variability around the central estimate of cost-effectiveness, as shown by the cost-effectiveness acceptability curve. CONCLUSION: The use of Sativex could improve the quality of life of patients with a reasonable incremental cost resulting as a cost-effective option for patients with MS-resistant spasticity. These results could help clinicians and decision makers to develop improved management strategies for spasticity in patients with MS, optimizing the use of available resources.

Clinical outcome indicators in chronic hepatitis B and C: A primer for value-based medicine in hepatology.

BACKGROUND & AIMS: Chronic liver diseases (CLDs) are major health problems that require complex and costly treatments. Liver-specific clinical outcome indicators (COIs) able to assist both clinicians and administrators in improving the value of care are presently lacking. The Value-Based Medicine in Hepatology (VBMH) study aims to fill this gap, devising and testing a set of COIs for CLD, that could be easily collected during clinical practice. Here we report the COIs generated and recorded for patients with HBV or HCV infection at different stages of the disease. METHODS/RESULTS: In the first phase of VBMH study, COIs were identified, based on current international guidelines and literature, using a modified Delphi method and a RAND 9-point appropriateness scale. In the second phase, COIs were tested in an observational, longitudinal, prospective, multicentre study based in Lombardy, Italy. Eighteen COIs were identified for HBV and HCV patients. Patients with CLD secondary to HBV (547) or HCV (1391) were enrolled over an 18-month period and followed for a median of 4 years. The estimation of the proposed COIs was feasible in the real-word clinical practice and COI values compared well with literature data. Further, the COIs were able to capture the impact of new effective treatments like direct-acting antivirals (DAAs) in the clinical practice. CONCLUSIONS: The COIs efficiently measured clinical outcomes at different stages of CLDs. While specific clinical practice settings and related healthcare systems may modify their implementation, these indicators will represent an important component of the tools for a value-based approach in hepatology and will positively affect care delivery.

Stroke prevention, 1-year clinical outcomes and healthcare resource utilization in patients with atrial fibrillation in France: Data from the GARFIELD-AF registry.

BACKGROUND: GARFIELD-AF is a non-interventional worldwide study of adults with atrial fibrillation. AIMS: To analyse the characteristics of the 1399 patients recruited in France from August 2010 to July 2015, their 1-year outcomes and healthcare resource utilization. METHOD: Patients aged ≥18 years with newly diagnosed atrial fibrillation (≤6 weeks' duration) and ≥1 stroke risk factor were eligible. Patient demographics, medical history and antithrombotic treatment were recorded at baseline. The incidences of stroke/systemic embolism, major bleeding, all-cause mortality, cardiovascular and non-cardiovascular mortality, new acute coronary syndrome and congestive heart failure were recorded during a 1-year follow-up. RESULTS: The median age was 76.0 years; 44.5% of patients were female. The median CHA2DS2-VASc and HAS-BLED scores were 4.0 and 2.0, respectively. At diagnosis, 78.9% of patients received anticoagulant therapy±antiplatelet therapy; more patients received vitamin K antagonists (VKAs; 46.0%) than direct oral anticoagulants (DOACs; 32.9%). The median proportion of time in the therapeutic range for VKAs was 65.6%. Between 2010 and 2015, anticoagulant prescription increased, driven by the growing use of DOACs±antiplatelet therapy (1.1% to 50.0%), whereas prescription of VKAs±antiplatelet therapy decreased (74.4% to 32.3%). All-cause mortality was the most frequent event (6.75 per 100 person-years). Risk-adjusted event rates for France showed that stroke/systemic embolism and all-cause mortality occurred more frequently than in GARFIELD-AF overall, whereas the rates of major bleeding were similar. In terms of healthcare resource utilization, the highest cost was associated with inpatients. CONCLUSIONS: Patients enrolled in France had higher rates of mortality and stroke/systemic embolism than in GARFIELD-AF overall. Conversely, the risk of major bleeding was not higher.

Peripheral arterial disease in diabetic patients: a long-term population-based study on occurrence, outcomes and cost.

BACKGROUND: Diabetes mellitus (DM) is a highly prevalent disease with severe long-term consequences, and a known risk factor for peripheral artery disease (PAD). These two diseases combined are responsible for high morbidity and mortality. The aim of this study is to investigate the burden of PAD in patients with DM, the effect of revascularization on outcomes, and geographical variation in the access to PAD courses of treatment. METHODS: From the healthcare claims of the Lombardy residents (16% of the Italian population) we identified diabetic patients with PAD as the study population, distinguishing between patients who received revascularization procedures (Revasc) and those who did not (NoRevasc). Patients were classified by sex, age, comorbidities, mortality, amputation received and direct healthcare cost. RESULTS: The DM with PAD study population consisted of 18,344 patients (61% male), aged on average 72 (±10.1) years. Most of them (64%) did not receive any revascularization procedures and 12% of the latter had at least one major amputation. The major amputation rate was significantly lower for the Revasc group when compared to the NoRevasc group. Geographical heterogeneity in DM and PAD occurrences as well as in revascularization procedures was detected in the area under study. CONCLUSIONS: The present study gives an up-to-date description of the dramatic epidemiologic and economic burden of PAD in diabetic subjects using a truly population-based data and longitudinal follow-up of up to 9 years. It represented a useful tool to evaluate the impact of revascularization and to provide evidence of different outcomes associated with different levels of access to services.

Benefits in pain perception, ability function and health-related quality of life in patients with failed back surgery syndrome undergoing spinal cord stimulation in a clinical practice setting.

BACKGROUND: Failed back surgery syndrome (FBSS) represents one main cause of chronic neuropathic or mixed pain, functional disability and reduced Health Related Quality of Life (HRQoL). Spinal Cord Stimulation (SCS) can be a value for money option to treat patients refractory to conventional medical management (CMM). We estimated from real-world data: 1) the amount of reduced levels of HRQoL of target patients compared to general population, 2) the relationship between pain intensity, functional disability, and overall HRQoL, and 3) the improvement of patients' health from SCS intervention, and 4) we give some insights and make some suggestions on the selection of a battery of patients' reported health instruments for use in routine clinical practice. METHODS: At recruitment (before SCS) and every 6 months for 2 years after SCS a battery of questionnaires/tests were completed: the generic EQ-5D and SF-36 for HRQoL, the specific Numerical Rating Scale (NRS) to measure pain intensity, and Oswestry Disability Index (ODI) to measure functional disability. We conducted multilevel regression analyses to investigate the association of HRQoL with the NRS and ODI indexes; multiple regression analyses to compare EQ-5D data with those of the general population adjusted for age, sex and education, and statistical tests to compare the changes of HRQoL, NRS and ODI estimates at baseline with those measured during the follow-up. RESULTS: Eighty patients (40% male, mean age = 58 years) participated. HRQoL was significantly worse in the patients than in the corresponding general population. Pain, functional disability and HRQoL significantly related each other during follow-up, Significant improvements (p < 0.001) in pain intensity, functional capability and HRQoL were reached after 6 months from SCS and generally remained stable during follow-up. Specific instruments provided detailed information on disability and pain, while generic instruments assessed the overall HRQoL and allowed a comparison with the general population's one. CONCLUSIONS: SCS + CMM treatment reaches a statistically significant and probably a clinically relevant improvement in pain perception, functional disability and HRQoL in patients with FBSS refractory to CMM. An appropriate selection of instruments for use in clinical practice is crucial for a routine assessment of health perception in patients, aimed to guide decisions for optimal treatment.

Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation is increasingly recognised as a rescue therapy for refractory cardiac arrest, nevertheless data are scanty about its effects on neurologic and cardiac outcome. The aim of this study is to compare clinical outcome in patients with cardiac arrest of ischaemic origin (i.e. critical coronary plaque during angiography) and return of spontaneous circulation during conventional cardiopulmonary resuscitation vs refractory cardiac arrest patients needing extracorporeal cardiopulmonary resuscitation. Moreover, we tried to identify predictors of survival after successful cardiopulmonary resuscitation. METHODS: We enrolled 148 patients with ischaemic cardiac arrest admitted to our hospital from 2011-2015. We compared clinical characteristics, cardiac arrest features, neurological and echocardiographic data obtained after return of spontaneous circulation (within 24 h, 15 days and six months). RESULTS: Patients in the extracorporeal cardiopulmonary resuscitation group ( n=63, 43%) were younger (59±9 vs 63±8 year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those with conventional cardiopulmonary resuscitation. In the extracorporeal cardiopulmonary resuscitation group, left ventricular ejection fraction was lower than conventional cardiopulmonary resuscitation at early echocardiography (19±16% vs 37±11 p<0.01). Survivors in both groups showed similar left ventricular ejection fraction 15 days and 4-6 months after cardiac arrest (46±8% vs 49±10, 47±11% vs 45±13%, p not significant for both), despite a major extent and duration of cardiac ischaemia in extracorporeal cardiopulmonary resuscitation patients. At multivariate analysis, the total cardiac arrest time was the only independent predictor of survival. CONCLUSIONS: Extracorporeal cardiopulmonary resuscitation patients are younger and have less comorbidities than conventional cardiopulmonary resuscitation, but they have worse survival and lower early left ventricular ejection fraction. Survivors after extracorporeal cardiopulmonary resuscitation have a neurological outcome and recovery of heart function comparable to subjects with return of spontaneous circulation. Total cardiac arrest time is the only predictor of survival after cardiopulmonary resuscitation in both groups.

Epidemiologic and Economic Burden Attributable to First Spinal Fusion Surgery: Analysis From an Italian Administrative Database.

STUDY DESIGN: Retrospective large population based-study. OBJECTIVE: Assessment of the epidemiologic trends and economic burden of first spinal fusions. SUMMARY OF BACKGROUND DATA: No adequate data are available regarding the epidemiology of spinal fusion surgery and its economic impact in Europe. METHODS: The study population was identified through a data warehouse (DENALI), which matches clinical and economic data of different Healthcare Administrative databases of the Italian Lombardy Region. The study population consisted of all subjects, resident in Lombardy, who, during the period January 2001 to December 2010, underwent spinal fusion surgery (ICD-9-CM codes: 81.04, 81.05, 81.06, 81.07, and 81.08). The first procedure was used as the index event. We estimated the incidence of first spinal fusion surgery, the population and surgery characteristics and the healthcare costs from the National Health Service's perspective. The analysis was performed for the entire population and divided into the main groups of diagnosis. RESULTS: The analysis identified 17,772 [mean age (SD): 54.6 (14.5) years, 55.3% females] spinal fusion surgeries. Almost 67% of the patients suffered from a lumbar degenerative disease. The incidence rate of interventions increased from 11.5 to 18.5 per 100,000 person-year between 2001 and 2006, and was above 20.0 per 100,000 person-year in the last 4 years. The patients' mean age increased during the observational time period from 48.1 to 55.9 years; whereas the median hospital length of stay reported for the index event decreased. The average cost of the spinal fusion surgery increased during the observational period, from &OV0556; 4726 up to &OV0556; 9388. CONCLUSION: The study showed an increasing incidence of spinal fusion surgery and costs from 2001 to 2010. These results can be used to better understand the epidemiological and economic burden of these interventions, and help to optimize the resources available considering the different clinical approaches accessible today. LEVEL OF EVIDENCE: 4.

Study on Potential Clostridium Botulinum Growth and Toxin Production in Parma Ham.

The objective of this study was to investigate Clostridium botulinum growth and toxin production in the industrially manufactured Italian Parma ham. The study focuses on the Parma ham production phase identified as maximum risk to C. botulinum proliferation, i.e. the transition from cold phase (salting and resting) to a phase carried out at temperature between 15 and 23°C (drying). A preliminary in vitro test was carried out in order to verify the capability of 6 C. botulinum strains (1 type A, 4 type B, and 1 type E strains) to grow in conditions of temperature, pH and NaCl concentration comparable to those of the beginning stage of ham drying. Five C. botulinum strains grew at 20°C and pH 6, four strains produced toxin when inoculated at a concentration equal to 103 cfu/mL at NaCl concentration of 4%, while when the inoculum concentration was 10 cfu/mL, NaCl concentration of 3% resulted the toxin-genesis limiting factor. An experimental contamination with a mixture of the 5 C. botulinum strains selected by the preliminary in vitro test was performed on 9 thighs inoculated at the end of the resting phase. The study was designed to evaluate the potential growth and toxin production in extremely favourable conditions for the bacterium. Type B proteolytic C. botulinum toxin was produced after 14 days of incubation at 20°C in 2 thighs characterised by high weight, low number of days of resting and anomalous physiochemical characteristics [one for very low NaCl concentration (1.59%), the other for elevated pH (6.27) and both for high water activity values (>0.970)]. The results of this research confirm that the cold resting step is a critical phase in the production process of Parma ham for the investigated hazard. Based on the present study, the long resting phase adopted in the manufacturing of Parma ham is proven effective to prevent the growth of C. botulinum, an event which could not otherwise be excluded if the hams were processed under less stringent technological conditions.

Processing-Dependent and Clonal Contamination Patterns of Listeria monocytogenes in the Cured Ham Food Chain Revealed by Genetic Analysis.

The quantitative and qualitative patterns of environmental contamination by Listeria monocytogenes were investigated in the production chain of dry-cured Parma ham. Standard arrays of surfaces were sampled in processing facilities during a single visit per plant in the three compartments of the food chain, i.e., ham production (19 plants) and postproduction, which was divided into deboning (43 plants) and slicing (25 plants) steps. The numbers of sampled surfaces were 384 in ham production, with 25 positive for L. monocytogenes, and 1,084 in postproduction, with 83 positives. Statistical analysis of the prevalence of contaminated surfaces showed that in ham production, contamination was higher at the beginning of processing and declined significantly toward the end, while in postproduction, prevalence rose toward the end of processing. Prevalence was higher in the deboning facilities than in slicing facilities and was dependent on the type of surface (floor/drainage > clothing > equipment). The qualitative pattern of contamination was investigated through an analysis of the survey isolates and a set of isolates derived from routine monitoring, including longitudinal isolations. Pulsed-field gel electrophoresis (PFGE) and whole-genome single-nucleotide polymorphism (SNP) analysis revealed a remarkable clonality of L. monocytogenes within plants, with the detection of 16 plant-specific clones out of 17 establishments with multiple isolates. Repeated detections of clonal isolates >6 months apart were also observed. Six was the maximum number of between-isolate differences in core SNPs observed within these clones. Based on the same six-SNP threshold, three clusters of clonal isolates, shared by six establishments, were also identified. The spread of L. monocytogenes within and between plants, as indicated by its clonal behavior, is a matter of concern for the hygienic management of establishments.