Investigating socioeconomic disparities in lung cancer diagnosis, treatment and mortality: an Italian cohort study.

BACKGROUND: Lung cancer is one of the most lethal cancers worldwide and patient clinical outcomes seem influenced by their socioeconomic position (SEP). Since little has been investigated on this topic in the Italian context, our aim was to investigate the role of SEP in the care pathway of lung cancer patients in terms of diagnosis, treatment and mortality. METHODS: This observational retrospective cohort study included patients discharged in the Lazio Region with a lung cancer diagnosis between 2014 and 2017. In the main analysis, educational level was used as SEP measure. Multivariate models, adjusted for demographic and clinical variables, were applied to evaluate the association between SEP and study outcomes, stratified for metastatic (M) and non-metastatic (NM) cancer. We defined a diagnosis as 'delayed' when patients received their initial cancer diagnosis after an emergency department admission. Access to advanced lung cancer treatments (high-cost, novel and innovative treatments) and mortality were investigated within the 24-month period post-diagnosis. Moreover, two additional indicators of SEP were examined in the sensitivity analysis: one focusing on area deprivation and the other on income-based exemption. RESULTS: A total of 13,251 patients were identified (37.3% with metastasis). The majority were males (> 60%) and over half were older than 70 years. The distribution of SEP levels among patients was as follow: 31% low, 29% medium-low, 32% medium-high and 7% high. As SEP increased, the risks of receiving a delayed diagnosis ((high vs low: M: OR = 0.29 (0.23-0.38), NM: OR = 0.20 (0.16-0.25)) and of mortality ((high vs low M: OR = 0.77 (0.68-0.88) and NM: 0.61 (0.54-0.69)) decreased. Access to advanced lung cancer treatments increased in accordance with SEP only in the M cohort (high vs low: M: OR = 1.57 (1.18-2.09)). The primary findings were corroborated by sensitivity analysis. CONCLUSIONS: Our study highlighted the need of public health preventive and educational programs in Italy, a country where the care pathway of lung cancer patients, especially in terms of diagnosis and mortality, appears to be negatively affected by SEP level.

Monitoring medicine prescriptions before, during and after pregnancy in Italy.

BACKGROUND: The use of medications during pregnancy is a common event worldwide. Monitoring medicine prescriptions in clinical practice is a necessary step in assessing the impact of therapeutic choices in pregnant women as well as the adherence to clinical guidelines. The aim of this study was to provide prevalence data on medication use before, during and after pregnancy in the Italian population. METHODS: A retrospective prevalence study using administrative healthcare databases was conducted. A cohort of 449,012 pregnant women (15-49 years) residing in eight Italian regions (59% of national population), who delivered in 2016-2018, were enrolled. The prevalence of medication use was estimated as the proportion (%) of pregnant women with any prescription. RESULTS: About 73.1% of enrolled women received at least one drug prescription during pregnancy, 57.1% in pre-pregnancy and 59.3% in postpartum period. The prevalence of drug prescriptions increased with maternal age, especially during the 1st trimester of pregnancy. The most prescribed medicine was folic acid (34.6%), followed by progesterone (19%), both concentrated in 1st trimester of pregnancy (29.2% and 14.8%, respectively). Eight of the top 30 most prescribed medications were antibiotics, whose prevalence was higher during 2nd trimester of pregnancy in women ≥ 40 years (21.6%). An increase in prescriptions of anti-hypertensives, antidiabetics, thyroid hormone and heparin preparations was observed during pregnancy; on the contrary, a decrease was found for chronic therapies, such as anti-epileptics or lipid-modifying agents. CONCLUSIONS: This study represents the largest and most representative population-based study illustrating the medication prescription patterns before, during and after pregnancy in Italy. The observed prescriptive trends were comparable to those reported in other European countries. Given the limited information on medication use in Italian pregnant women, the performed analyses provide an updated overview of drug prescribing in this population, which can help to identify critical aspects in clinical practice and to improve the medical care of pregnant and childbearing women in Italy.

Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study.

INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.

Drug Prescriptions among Italian and Immigrant Pregnant Women Resident in Italy: A Cross-Sectional Population-Based Study.

Ensuring drug safety for pregnant women through prescription drug monitoring is essential. The aim of this study was to describe the prescription pattern of medicines among pregnant immigrant women from countries with high migratory pressure (HMPCs) compared to pregnant Italian women. The prevalence of drug prescriptions among the two study populations was analysed through record linkage procedures applied to the administrative databases of eight Italian regions, from 2016 to 2018. The overall prevalence of drug prescription was calculated considering all women who received at least one prescription during the study period. Immigrants had a lower prevalence of drug prescriptions before (51.0% vs. 58.6%) and after pregnancy (55.1% vs. 60. 3%). Conversely, during pregnancy, they obtained a slightly higher number of prescriptions (74.9% vs. 72.8%). The most prescribed class of drugs was the blood and haematopoietic organs category (category ATC B) (56.4% vs. 45.9%, immigrants compared to Italians), followed by antimicrobials (31.3% vs. 33.7%). Most prescriptions were appropriate, while folic acid administration 3 months before conception was low for both study groups (3.9% immigrants and 6.2% Italians). Progesterone seemingly was prescribed against early pregnancy loss, more frequently among Italians (16.5% vs. 8.1% immigrants). Few inappropriate medications were prescribed among antihypertensives, statins and anti-inflammatory drugs in both study groups.

Medication prescriptions before, during and after pregnancy in Italy: a population-based study.

BACKGROUND: Monitoring medicine prescriptions in pregnancy is an aspect of extreme interest in term of public health. METHODS: A retrospective prevalence study using administrative healthcare databases was performed in order to evaluate medication prescriptions in Italy. A cohort of 274,938 pregnant women (15-49 years) residing in three Italian regions (Emilia-Romagna, Lazio, Puglia), who delivered in 2014-2017, were enrolled. The prevalence of medication use was estimated as the proportion of pregnant women with any medication prescription in each of the following five trimesters: 1 before pregnancy (pre-T), 3 during pregnancy (1st TP, 2nd TP, 3rd TP) and 1 after pregnancy (post-T). RESULTS: About 80% of enrolled pregnant women received at least one prescription during pregnancy, 36.5% before pregnancy and 50.7% in the post-partum. The most prescribed medicine was folic acid (42%), mostly used in 1st TP (35%). Progesterone use was concentrated in 1st TP (19%) and increased as the number of previous abortions. Pregnancy use of antidiabetics, antihypertensives, and thyroid preparations were 24.1‰, 21.5‰, 101.8‰, respectively. CONCLUSIONS: At the national level, this study confirmed the prescriptive trend observed in other European studies, but a regional variability for all medication groups was found. Further studies are needed in order to identify determinants of medication prescriptions during pregnancy in Italy.

Determinants of first-line biological treatment in patients with rheumatoid arthritis: Results from an observational study.

ABSTRACT: Guidelines for the treatment of rheumatoid arthritis (RA) recommend the use of conventional synthetic disease modifying anti-rheumatic drugs (cs-DMARDs) at the onset of the disease and only in the case of therapeutic failure, the addition of a biological drug (b-DMARD) is suggested.The study aimed to evaluate determinants for first-line biological treatment in patients with RA in clinical practice.A cohort of patients with RA, resident in Lazio, a central Italian Region, where Rome is located, and with at least one disease modifying anti-rheumatic drugs (DMARD) prescription between 2010 and 2016 was selected using health information systems linkable with each other by an individual unique anonymous identifier. In particular RA cohort was defined retrieving all patients with at least a RA disease code in regional data claims (hospital discharge, exemption code, emergency department access, or therapeutic plan). Only new users were included and the first-line treatment was identified: cs-DMARD or b-DMARD.Descriptive analysis according to type of DMARD treatment was performed. Through multivariate logistic regression models (odds ratio [OR]; confidence interval [CI95%]) determinants of therapy such as age, comorbidity, and comedication were investigated.Finally, switching during the first year of treatment from cs-DAMARDs to b-DMARDs was analyzed.DMARD-new users with RA were 5641; 7.1% of them with b-DMARD as first-line treatment. Considering the year of dispensing, this percentage ranged from 4.9% (2011) to 8.2% (2015). Among cs-DMARD the most prescribed active agent was methotrexate (59.3%), while among b-DMARD it was etarnecept (37.0%), followed by adalimumab (21.2%). The average age of the cohort was 54 years with 77% of women. Determinants of first-line b-DMARD use were: age (OR<30vs>65 = 3.7; 2.6-5.2, OR[30-45)vs>65 = 1.7; 1.2-2.4, OR[45-55)vs>65 = 1.6; 1.1-2.4, OR[55-65)vs>65 = 1.2; 0.8-1.7), cancers (OR = 2.3; 1.3-4.2), cardio-cerebrovascular disease (OR = 1.4; 1.0-1.9), use of non-steroidal anti-inflammatory drugs (NSAIDs) (OR = 0.6; 0.4-0.7) and corticosteroids (OR = 0.6; 0.5-0.7) in the 6 months preceding diagnosis.In the first year of treatment, we observed a percentage of switch from cs-DMARDs to b-DMARDs of 7.9%.In clinical practice, about 7% of patients with RA are prescribed with a b-DMARD as first-line treatment. This therapeutic option, even if not supported by guide lines, is mostly link to younger age and clinical profile of the patients.

[Appropriate use of trastuzumab in Lazio Region: therapeutic scenarios and estimation of possible savings for the Regional Health Service.] / Utilizzo appropriato del trastuzumab nel Lazio: scenari terapeutici e stima del possibile risparmio per il Servizio Sanitario Regionale.

BACKGROUND: The availability of subcutaneous (SC) and intravenous (EV) formulations of trastuzumab and the recent release of the biosimilar EV version (10/2018) increase the offer for the treatment of patients with breast or gastric cancer HER2 positive. In this context, it is necessary to build therapeutic scenarios form avalible data in order to estimate the potential savings for the Regional Health Service (RHS) taking into account the appropriateness of use and patient's preferences. AIM: To evaluate the available comparative evidence regarding the effectiveness and safety of the different trastuzumab formulations; to analyze the supply of trastuzumab by type of administration (EV/SC) in Lazio in 2018, identifying the most appropriate use; to hypothesize a cost-effective scenario for the Regional Health Service (SSR) in 2019. Mehods. With the working group formed by clinicians and methodologists, we analysed the evidence of efficacy and safety available to date for the different formulations of trastuzumab, also taking into account the recent availability of biosimilars and with particular regard to the phenomenon of the potential switch between different therapeutic options. In addition, for the year 2019 the available economic impact assessments were also simulated with data from the Lazio Region. Through the datas from direct pharmaceutical products, the transtuzumab cycles supplied in 2018 were identified separately for the available formulations (EV/SC). For each cycle of therapy, starting from the date of delivery, the possible presence of a concomitant treatment (± 2 days) was investigated, tracing the type and method of administration. The treatments (concomitant with trastuzumab) were identified for which there were conflicting modes of administration. In addition, the supply of SC per dispensing structure was evaluated and, on the basis of this information, a scenario of use was hypothesized that takes into account costs and plausible consumption. RESULTS: A review of the literature summarized the available evidence on the efficacy and safety of the use of trastuzumab in the recorded therapeutic indications. The review was discussed with the working group and used to reproduce, at regional level, the estimates of the economic impact of the different therapeutic choices possible with trastuzumab. As regards the data on the use of trastuzumab, in the Lazio Region in 2018, 22,214 treatment cycles were observed (at a cost of 33 million euro) for 2,407 patients; new users accounted for 52.2%. 46.8% of the cycles were administered via SC; the use of the biosimilar was observed from October onwards and involved 143 cycles (0.6%). In 68.4% of the cycles trastuzumab was administered in monotherapy; among the therapies associated with trastuzumab, the most frequent was pertuzumab (n=4,258, 19.2% of the total cycles), followed by paclitaxel (n=1,364, 6.1% of the total cycles). Among the cycles of trastuzumab in concomitant therapy (N=7,022), 17.3% was administered via SC despite the presence of other drugs administered via EV. The prescriptive pattern of trastuzumab was heterogeneous for the different delivery structures. The SC administration presents a variability in the supply from 26% to 70% (interquartile range) and does not seem to be related to the type and volume of activity of the hospital. If the biosimilar EV is expected to account for 55% of consumption by 2019, thus reducing the use of the EV originator to 10% and the SC originator to 35%, savings of more than €7 million. CONCLUSIONS: Through the use data of the different formulations available for trastuzumab and taking into account the prescriptive appropriateness (and patient preferences), it has been possible to identify a SSR scenario of economic convenience due to the greater use of the biosimilar.

Neonatal outcomes following new reimbursement limitations on palivizumab in Italy.

OBJECTIVE: To evaluate the impact of new reimbursement decisions for palivizumab treatment on respiratory syncytial virus (RSV) hospitalisations and the concomitant number of palivizumab prescriptions for infants aged <2 years. DESIGN: We compared the RSV hospitalisation rates in infants before and after implementation of new limitations during three RSV seasons 2014-2017. SETTING: Population aged <2 years at the beginning of each RSV seasons extracted from regional health systems (Lazio region, 2016, 5 898 124 inhabitants and 47 595 births). PATIENTS: Out of 70 323 infants, 5895 (8.4%) premature babies (gestational age (GA) <37 weeks) were followed before-after Italian Medicines Agency (AIFA)-2016 limitations. INTERVENTION: In 2016, AIFA, following the American Academy of Pediatrics guidelines, decided to limit coverage of palivizumab prophylaxis (GA ≤29 weeks). MAIN OUTCOMES MEASURES: Trend of hospitalisations by months and rate of RSV before-after new restrictions were analysed. Palivizumab prescriptions and costs for National Health Service (NHS) were considered. RESULTS: In a population of 284 902 aged <2 years, the number of hospitalisations due to RSV infection was 1729. Following AIFA-2016 limitations, a reduction in the number of RSV infection-based hospitalisations from 6.3/1000 (95% CI 6.0 to 6.7) to 5.5/1000 (95% CI 5.0 to 5.9) was observed. Palivizumab showed a concomitant reduction of 48% in the number of prescriptions (saving €750 000 for the NHS). No differences of GA, age on admission or severity of RSV infection were observed. CONCLUSIONS: Implementation of the new palivizumab reimbursement criteria was not associated with an increase in the RSV hospitalisation rate for children aged <2 years despite a significant reduction in the number of palivizumab prescriptions.

[Socioeconomic position and appropriate antiplatelet therapy after percutaneous coronary intervention: a population-based cohort study in Rome (Lazio Region, Central Italy)]. / Posizione socioeconomica e aderenza alla terapia antiaggregante post angioplastica coronarica: uno studio epidemiologico a Roma.

OBJECTIVES: to evaluate the association between socioeconomic position (SEP) and adherence to appropriate antiplatelet therapy (AAT) after percutaneous coronary intervention (PCI) in the year following the discharge. DESIGN: according to scientific guidelines, AAT for PCI patients consists of Clopidogrel for a minimum of 1 month and ideally up to 12 months after discharge, and with Acetylsalicylic Acid (ASA) indefinitely. For each patient, drug claims over a 1-year period after discharge were retrieved from Regional Drug Dispense Registry. Drug use was measured with Proportion of Days Covered (PDC). PDC was computed dividing the total number of dispensed Defined Daily Dose by each patient's follow-up time. Dual antiplatelet therapy with PDC ≥75% and single therapy based on Clopidogrel with PDC ≥75% were considered as AAT. We used a composite area-based index of socioeconomic position by census block of residence built using the 2001 census of Rome, assuming 5 levels (from 1 =High SEP to 5 =Low SEP). SETTING AND PARTICIPANTS: study population of 5,901 patients resident in Rome, who underwent their first PCI during 2006-2007 were selected from the Hospital Information System. MAIN OUTCOME MEASURES: proportions of patients treated with AAT by SEP was measured for the overall year and by semester. The association between SEP and adherence to AAT was estimated through logistic regression models adjusting for factors selected by a stepwise procedure (gender, age, comorbidities, discharged from cardiology or coronary care unit, new user of antiplatelet drugs). RESULTS: 76% of the study population were men, 96% were aged more than 44 years, and 63% belonged to medium-low SEP. In the 1-year follow-up, the proportion of patients adherent to appropriate antiplatelet therapy was 65%; SEP was associated with AAT (OR high vs. low SEP 1.26; 95%CI 1.05-1.51; p trend =0.002). CONCLUSIONS: during the year after discharge, adherence to AAT of PCI patients was unsatisfactory and it decreased overtime more in medium-low SEP patients than in high SEP patients. Strategies to improve adherence to AAT among patients who underwent PCI need to be identified taking into account the multifactorial nature of poor medication adherence, and in particular patients' socioeconomic position.

Effects of socioeconomic position on 30-day mortality and wait for surgery after hip fracture.

OBJECTIVE: In countries where the National Health Service provides universal health coverage, socioeconomic position should not influence the quality of health care. We examined whether socioeconomic position plays a role in short-term mortality and waiting time for surgery after hip fracture. DESIGN: Retrospective cohort study. SETTING: and participants From the Hospital Information System database, we selected all patients, aged at least 65 years and admitted to acute care hospitals in Rome for a hip fracture between 1 January 2006 and 30 November 2007. The socioeconomic position of each individual was obtained using a city-specific index of socioeconomic variables based on the individual's census tract of residence. MAIN OUTCOME MEASURES: Three different outcomes were defined: waiting times for surgery, mortality within 30 days and intervention within 48 h of hospital arrival for hip fracture. We used a logistic regression to estimate 30-day mortality and a Cox proportional hazard model to calculate hazard ratios of intervention within 48 h. Median waiting times were estimated by adjusted Kaplan-Meyer curves. Analyses were adjusted for age, gender and coexisting medical conditions. RESULTS: Low socioeconomic level was significantly associated with higher risk of mortality [adjusted relative risk (RR) = 1.51; P < 0.05] and lower risk of early intervention (adjusted RR = 0.32; P < 0.001). Socioeconomic level had also an effect on waiting times within 30 days. CONCLUSIONS: Individuals living in disadvantaged census tracts had poorer prognoses and were less likely than more affluent people to be treated according to clinical guidelines despite universal healthcare coverage.

Temporal and geographic heterogeneity of the association between socioeconomic position and hospitalisation in Italy: an income based indicator.

BACKGROUND: The inverse association between socioeconomic position (SEP) and health has been extensively explored in Italy; however few studies have been carried out on the relationship between income inequalities and health status or health services utilisation, particularly at a local level.The objective of this study is to test the association between the demand for hospital care and a small area indicator based on income in four Italian cities, over a four-year period (1997-2000), in the adult population. METHODS: Census Block (median 260 residents) Median per capita Income (CBMI) was computed through record linkage between 1998 national tax and local population registries in the cities of Rome, Turin, Milan and Bologna (total population approximately 5.5 million). CBMI was linked to acute hospital discharges among residents, based on patient's residence.Age-standardized gender-specific hospitalisation rates were computed by CBMI quintiles (first quintile indicating lowest income), overall, and by city and year. Heterogeneity of the association between income level and hospitalisation was analysed through a Poisson model. RESULTS: We found an inverse association between small area income level and hospitalisation rates, which decreased continuously from 153 per 1000 inhabitants in the first quintile to 107 per 1000 inhabitants in the fifth quintile. Income differences in hospitalisation were confirmed in each city and year. However, the magnitude of the association and the absolute level of hospitalisation rates were quite different in each city and tended to slightly decrease over time in all cities considered, except Bologna. CONCLUSION: Our study confirms an inverse association between income level and the use of hospitalization in four Italian cities, using a small area economic indicator, based on population tax data. Further analysis of the association between income and cause-specific hospitalization rates will allow to better understand the capability of the Italian National Health System to compel with socio-economic inequalities in health needs.Furthermore the SEP indicator we propose can represent a contribution to the improvement of tools for monitoring inequalities in health and in health services utilization.

Changing pattern of drug abuse among patients entering treatment in Lazio, Italy, between 1996 and 2003: transition from heroin to cocaine use.

AIM: This study describes temporal changes of the pattern of substance abuse among drug users in treatment in Lazio, Italy. METHODS: We used individual data from the surveillance system of drug users of the Lazio region. We measured temporal changes in: the number of drug users in treatment, main and any substance of abuse, and mode of referral to treatment. RESULTS: Among new clients, the proportion of heroin use decreased from 78.2% in 1996 to 37.6% in 2003 (p < 0.0001), while cocaine use increased from 4.1% in 1996 to 30.1% in 2003 (p < 0.0001). In 2003, any use of cocaine was reported by 43.1% of new cases as compared to 38.9% taking heroin, 36.8% cannabis and 5.3% other substances, 41.9% using more than one substance. In 2003, 37.7% of new patients were referred to treatment by the police as compared to 10.4% in 1996. CONCLUSIONS: Heroin use has been replaced by cocaine among people coming to treatment centres for the first time. The main mode of access to treatment of new cocaine and cannabis users occurred through mandatory referral by the police. Routine surveillance systems of treatment demand are essential to monitor temporal trends of patterns of drug use in order to plan proper treatment strategies.

Socioeconomic status and hospitalization in the very old: a retrospective study.

BACKGROUND: Socioeconomic status could affect the demand for hospital care. The aim of the present study was to assess the role of age, socioeconomic status and comorbidity on acute hospital admissions among elderly. METHODS: We retrospectively examined the discharge abstracts data of acute care hospital admissions of residents in Rome aged 75 or more years in the period 1997-2000. We used the Hospital Information System of Rome, the Tax Register, and the Population Register of Rome for socio-economic data. The rate of hospitalization, modified Charlson's index of comorbidity, and level of income in the census tract of residence were obtained. Rate ratios and 95% confidence limits were computed to assess the relationship between income deciles and rate of hospitalization. Cross-tabulation was used to explore the distribution of the index of comorbidity by deciles of income. Analyses were repeated for patients grouped according to selected diseases. RESULTS: Age was associated with a marginal increase in the rate of hospitalization. However, the hospitalization rate was inversely related to income in both sexes. Higher income was associated with lower comorbidity. The same associations were observed in patients admitted with a principal diagnosis of chronic condition (diabetes mellitus, heart failure, chronic obstructive pulmonary disease) or stroke, but not hip fracture. CONCLUSION: Lower social status and associated comorbidity, more than age per se, are associated with a higher rate of hospitalization in very old patients.