Socio-economic inequalities in the use of drugs for the treatment of chronic diseases in Italy.

BACKGROUND: Since the use of medicines is strongly correlated to population health needs, higher drug consumption is expected in socio-economical deprived areas. However, no systematic study investigated the relationship between medications use in the treatment of chronic diseases and the socioeconomic position of patients. The purpose of the study is to provide a description, both at national level and with geographical detail, of the use of medicines, in terms of consumption, adherence and persistence, for the treatment of major chronic diseases in groups of population with different level of socioeconomic position.  METHODS: A cross-sectional study design was used to define the "prevalent" users during 2018. A longitudinal cohort study design was performed for each chronic disease in new drug users, in 2018 and the following year. A retrospective population-based study, considering all adult Italian residents (i.e. around 50.7 million people aged ≥ 18 years). Different medications were used as a proxy for underlying chronic diseases: hypertension, dyslipidemia, osteoporosis, diabetes and chronic obstructive pulmonary disease. Only "chronic" patients who had at least 2 prescriptions within the same subgroup of drugs or specific medications during the year were selected for the analysis. A multidimensional measures of socio-economic position, declined in a national deprivation index at the municipality level, was used to identify and estimate the relationship with drug use indicators. The medicine consumption rate for each pharmacological category was estimated for prevalent users while adherence and persistence to pharmacologic therapy at 12 months were evaluated for new users. RESULTS: The results highlighted how the socioeconomic deprivation is strongly correlated with the use of medicines: after adjustment by deprivation index, the drug consumption rates decreased, mainly in the most disadvantaged areas, where consumption levels are on average higher than in other areas. On the other hand, the adherence and persistence indicators did not show the same trend. CONCLUSIONS: This study showed that drug consumption is influenced by the level of deprivation consistently with the distribution of diseases. For this reason, the main levers on which it is necessary to act to reduce disparities in health status are mainly related to prevention. Moreover, it is worth pointing out that the use of a municipal deprivation indicator necessarily generates an ecological bias, however, the experience of the present study, which for the first-time deals with the complex and delicate issue of equity in Italian pharmaceutical assistance, sets the stage for new insights that could overcome the limits.

Apremilast as a target therapy for nail psoriasis: a real-life observational study proving its efficacy in restoring the nail unit.

PURPOSE: Psoriasis, Psoriatic Arthritis and Nail psoriasis are chronic diseases that share a common underlying etiology of immunity dysregulation, enhanced activation of inflammatory pathways and remitting-relapsing course. Although nails represent a small percentage of the body surface involvement of this site can lead to impaired quality of life, severe discomfort and even result in permanent disability. Current therapeutic options for nail psoriasis include a variety of topical and systemic treatments although they are often reported as unsatisfactory from patients either due to their poor effectiveness or disturbing side effects. Recently small molecule drugs such as the PDE4 inhibitors were introduced in clinical practice and specifically apremilast has shown to be an effective new treatment option for psoriasis and psoriatic arthritis. Considering either the specific mechanism of action of apremilast, we performed a real-life observational study of 24 weeks assessing apremilast role in nail psoriasis. MATHERIALS AND METHODS: Patients received apremilast 30mg bid, orally. Safety and efficacy were assessed at weeks 0, 4, 8, 12 and 24 using Dermatologic Life Quality Index (DLQI) and Nail Area Psoriasis Severity Index (NAPSI). At T0 we took a nail sample to investigate the presence of onychomycosis. Culture tests were performed in all the patients to search for fungi. RESULTS: We recruited a total of 15 patients with nail psoriasis. The analysis of variance (one-way ANOVA) showed the following results: DLQI (F.15.7; p-value < .00001) and NAPSI (F.9.4; p-value < .00001). Three patients (20%) presented also onychomycoses at the beginning of the treatment. CONCLUSIONS: Apremilast showed fast and sustained improvement of nail psoriasis over time and a complete resolution of life quality impairment due to the disease.

Particulate matter air pollution components and risk for lung cancer.

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.

Air pollution and childhood leukaemia: a nationwide case-control study in Italy.

OBJECTIVES: Leukaemia is the most common cancer in children, but its aetiology is still poorly understood. We tested the hypothesis that traffic-related air pollution is associated with paediatric leukaemia because of chronic exposure to several potential carcinogens. METHODS: The Italian SETIL study (Study on the aetiology of lymphohematopoietic malignancies in children) was conducted in 14 Italian regions. All incident cases of leukaemia in children aged ≤10 years from these regions (period 1998-2001) were eligible for enrolment. Two controls per case, matched on birth date, gender and region of residence were randomly selected from the local population registries. Exposure assessment at birth residence included traffic indicators (distance to main roads and length of main roads within 100 m) and estimates of pollutants concentrations (particulate matter -PM2.5 and PM10- and gases -NO2 and O3-) from national dispersion model and land use regression models. The association between the exposure variables and leukaemia was assessed by logistic regression analyses. RESULTS: Participation rates were 91.4% among cases and 69.2% in controls; 620 cases (544 acute lymphocytic and 76 acute non-lymphocytic leukaemia) and 957 controls were included. Overall, when considering the residence at birth, 35.6% of cases and 42.4% of controls lived along busy roads, and the mean annual PM10 levels were 33.3 (SD=6.3) and 33.4 µg/m(3) (SD=6.5), respectively. No association was found, and all ORs, independent of the method of assessment and the exposure windows, were close to the null value. CONCLUSIONS: Using various exposure assessment strategies, air pollution appears not to affect the incidence of childhood leukaemia.

Assessing the public health impacts of urban air pollution in 25 European cities: results of the Aphekom project.

INTRODUCTION: The Aphekom project aimed to provide new, clear, and meaningful information on the health effects of air pollution in Europe. Among others, it assessed the health and monetary benefits of reducing short and long-term exposure to particulate matter (PM) and ozone in 25 European cities. METHOD: Health impact assessments were performed using routine health and air quality data, and a common methodology. Two scenarios were considered: a decrease of the air pollutant levels by a fixed amount and a decrease to the World Health Organization (WHO) air quality guidelines. Results were economically valued by using a willingness to pay approach for mortality and a cost of illness approach for morbidity. RESULTS: In the 25 cities, the largest health burden was attributable to the impacts of chronic exposure to PM2.5. Complying with the WHO guideline of 10 µg/m(3) in annual mean would add up to 22 months of life expectancy at age 30, depending on the city, corresponding to a total of 19,000 deaths delayed. The associated monetary gain would total some €31 billion annually, including savings on health expenditures, absenteeism and intangible costs such as well-being, life expectancy and quality of life. CONCLUSION: European citizens are still exposed to concentrations exceeding the WHO recommendations. Aphekom provided robust estimates confirming that reducing urban air pollution would result in significant health and monetary gains in Europe. This work is particularly relevant now when the current EU legislation is being revised for an update in 2013.

High-sensitivity cardiac troponin T for detection of subtle abnormalities of cardiac phenotype in a general population of elderly individuals.

OBJECTIVE: To investigate the association between circulating cardiac biomarkers and minor abnormalities in cardiac phenotype [left ventricular (LV) mass and midwall fractional shortening (MFS)] in elderly individuals in a general population sample. DESIGN AND SETTING: We examined the relationship between plasma concentrations of high-sensitivity cardiac troponin T (hs-cTnT) or N-terminal probrain natriuretic peptide (NT-proBNP) and elevated LV mass (LV mass/body surface area >95 g m(-2) for women and 115 g m(-2) for men), reduced MFS (<15%) or isolated LV diastolic dysfunction in 1973 elderly subjects (mean age 73 ± 5 years, range 65-84) resident in the Lazio region of Italy and enrolled in the PREDICTOR study. RESULTS: Overall, 24.8% of subjects had elevated LV mass, and 30.4% had reduced MFS. Median [quartile 1-3] plasma concentrations of hs-cTnT and NT-proBNP were higher in individuals with elevated than those with normal LV mass: 6.6 [3.5-11.6] and 147 [64-296] ng L(-1) vs. 4.6 [3.0-8.1] and 79 [41-151] ng L(-1) respectively (P < 0.001). There was a graded increase in median hs-cTnT concentrations across clinical categories of LV hypertrophy: 4.6 [3.0-8.1], 5.8 [3.1-10.2], 7.6 [3.8-13.7] and 8.4 [3.8-17.6] ng L(-1) for subjects with normal LV mass and mild, moderate or severe LV hypertrophy respectively (P < 0.0001); hs-cTnT also increased with increasing quartiles of MFS or grades of isolated LV diastolic dysfunction. CONCLUSIONS: Within an extremely low range of concentrations, increased hs-cTnT amongst community-dwelling elderly subjects is associated with subtle alterations in cardiac phenotype, suggesting that minor injury to cardiac myocytes and subsequent release of troponin reflect subclinical pathophysiological LV deterioration in this population.

The association of socioeconomic disadvantage with postoperative complications after major elective cardiovascular surgery.

BACKGROUND: Understanding the mechanism by which both patient- and hospital level factors act in generating disparities has important implications for clinicians and policy-makers. OBJECTIVE: To measure the association between socioeconomic position (SEP) and postoperative complications after major elective cardiovascular procedures. DESIGN: Multicity hospital-based study. SUBJECTS: Using Hospital Discharge Registries (ICD-9-CM codes), 19 310 patients were identified undergoing five cardiovascular operations (coronary artery bypass grafting (CABG), valve replacement, carotid endarterectomy, major vascular bypass, repair of unruptured abdominal aorta aneurysm (AAA repair)) in four Italian cities, 1997-2000. MEASURES: For each patient, a five-level median income index by census block of residence was calculated. In-hospital 30-day mortality, cardiovascular complications (CCs) and non-cardiovascular complications (NCCs) were the outcomes. Odds ratios (ORs) were estimated with multilevel logistic regression adjusting for city of residence, gender, age and comorbidities taking into account hospital and individual dependencies. MAIN RESULTS: In-hospital 30-day mortality varied by type of surgery (CABG 3.7%, valve replacement 5.7%, carotid endarterectomy 0.9%, major vascular bypass 8.8%, AAA repair 4.0%). Disadvantaged people were more likely to die after CABG (lowest vs highest income OR 1.93, p trend 0.023). For other surgeries, the relationship between SEP and mortality was less clear. For cardiac surgery, SEP differences in mortality were higher for publicly funded patients in low-volume hospitals (lowest vs highest income OR 3.90, p trend 0.039) than for privately funded patients (OR 1.46, p trend 0.444); however, the difference in the SEP gradients was not statistically significant. CONCLUSIONS: Disadvantaged people seem particularly vulnerable to mortality after cardiovascular surgery. Efforts are needed to identify structural factors that may enlarge SEP disparities within hospitals.

Comparison between various indices of exposure to traffic-related air pollution and their impact on respiratory health in adults.

OBJECTIVE: To evaluate the association of different indices of traffic-related air pollution (self-report of traffic intensity, distance from busy roads from geographical information system (GIS), area-based emissions of particulate matter (PM), and estimated concentrations of nitrogen dioxide (NO(2)) from a land-use regression model) with respiratory health in adults. METHODS: A sample of 9488 25-59-year-old Rome residents completed a self-administered questionnaire on respiratory health and various risk factors, including education, occupation, housing conditions, smoking, and traffic intensity in their area of residence. The study used GIS to calculate the distance between their home address and the closest high-traffic road. For each subject, PM emissions in the area of residence as well as estimated NO2 concentrations as assessed by a land-use regression model (R(2) value = 0.69), were available. Generalised estimating equations (GEE) were used to analyse the association between air pollution measures and prevalence of "ever" chronic bronchitis, asthma, and rhinitis taking into account the effects of age, gender, education, smoking habits, socioeconomic position, and the correlation of variables for members of the same family. RESULTS: Three hundred and ninety seven subjects (4% of the study population) reported chronic bronchitis, 472 (5%) asthma, and 1227 (13%) rhinitis. Fifteen per cent of subjects reported living in high traffic areas, 11% lived within 50 m of a high traffic road, and 28% in areas with estimated NO2 greater than 50 microg/m(3). Prevalence of asthma was associated only with self-reported traffic intensity whereas no association was found for the other more objective indices. Rhinitis, on the other hand, was strongly associated with all traffic-related indicators (eg, OR = 1.13, 95% CI: 1.04 to 1.22 for 10 microg/m(3) NO2, especially among non-smokers. CONCLUSIONS: Indices of exposure to traffic-related air pollution are consistently associated with an increased risk of rhinitis in adults, especially among non-smokers. The results for asthma are weak, possibly due to ascertainment problems.

Individual and area-based indicators of socioeconomic status and childhood asthma.

The current study evaluated the association between individual and area-based indicators of socioeconomic status and the prevalence, severity, and lifetime hospitalisation for asthma in children. The representative sample of 4,027 children from Rome, aged 6-7 yrs, used for the 1994 ISAAC (International Study on Asthma and Allergies in Childhood) initiative, was selected. Individual and small area indicators of socioeconomic status were used. Individual data on parents' education and on childhood asthma were gathered from self-administered parental questionnaires. Two small-area indicators (socioeconomic status index (SES) and average income in 1994) were derived using information available at the census tract of residence. Logistic regression models were used to estimate the association of parental education and small area indicators with asthma prevalence, severity, and hospitalisation. Parental smoking was considered in the analysis as a potential confounder. Prevalence of physician diagnosis of asthma (11.3%) increased as father's education decreased. Prevalence of severe asthma (1.6%) increased as maternal and paternal educational levels decreased. Lifetime hospitalisation for asthma (2.8%) was strongly associated with both parental education and small-area indicators of social disadvantage, even when considered simultaneously in the same logistic model. Socioeconomic conditions are associated with asthma occurrence, its severity, and hospitalisation. The association was stronger for asthma severity and hospitalisation. Individual indicators correlated better with the outcomes than area-based indicators. However, living in an underprivileged area is a strong independent predictor of hospital admission for asthma.

Hysterectomy and socioeconomic position in Rome, Italy.

STUDY OBJECTIVE: There exists conflicting evidence regarding the higher risk of hysterectomy among women of a lower educational and economic level. This study aims to assess whether in Italy socioeconomic level is related to hysterectomy undertaken for different medical reasons. DESIGN: An area based index was used to assign socieconomic status (SES; four levels defined) to 3141 women (aged 35 years or older) who underwent a hysterectomy in 1997 and were residing in Rome. Data were taken from hospital discharge records. Direct age standardised hospitalisation rates by SES level were calculated for overall hysterectomies and for those performed for either malignant or non-malignant causes. Statistical differences were detected using the ratios of standardised rates and the test for linear trend. MAIN RESULTS: The hysterectomy rate was 36.7 per 10 000 women aged 35 years or more. Hysterectomy for uterine leiomyoma accounted for 41% of all operations and was more frequent among women aged 35-49 years than for those aged 50 years or more (crude rates: 28.6 and 7.7 per 10 000, respectively). The risk of hysterectomy was 35% higher for the lowest SES group, compared with the highest group. No association was found between SES and hysterectomy rates for malignant causes, although less affluent women in age group 35-49 years had 87% higher risk of hysterectomy compared with most affluent women. The inverse association between SES and hysterectomy rates attributable to non-malignant causes was statistically significant for women aged 35-49 years but not for those aged 50 years or more. CONCLUSIONS: The inverse relation between hysterectomy and SES is largely attributable to benign disorders of the uterus, namely leiomyoma and prolapse. More affluent women may have a greater uptake of less invasive techniques for removing uterine leiomyoma compared with less affluent women, who are more likely to undergo unnecessary hysterectomies irrespective of their reproductive age.

[Health care inequalities: hospitalization and socioeconomic position in Rome]. / Diseguaglianze nell'assistenza sanitaria: ospedalizzazione e posizione socioeconomica a Roma.

Although the interest for equity is growing, scanty attention has been reserved so far in Italy to health care inequalities. The relation between hospitalization and socioeconomic position in Rome has been studied by evaluating overall heterogeneity and differences in access to effective non-discretionary treatments or at high degree of generic or specific inappropriateness. An area-based socioeconomic index was assigned to 86.4% out of 554.168 discharges of Rome residents identified during 1997 through the hospital information system. The analysis was performed by comparing standardized hospitalization rates across socioeconomic groups through linear trends and risk ratios. A significant inverse relation of overall hospitalization with socioeconomic position was observed for both acute admissions (+44% for most deprived males) and day hospital (+25%). No difference was found in use of effective treatments such as admissions in coronary care units for acute myocardical infarction or surgery for hip fractures. The inverse relation between socioeconomic position and acute hospitalization blunted in day hospital for inguinal hernia repair and actually reversed for cataract removal among females. The hospitalization risk for minor skin diseases, an ambulatory care sensitive condition, resulted inversely associated to socioeconomic position. An excess of hospitalization was also observed for poorest females undergoing appendectomy. Results indicate that observed heterogeneity between socioeconomic groups does not depend only on different health needs but also on an unequal utilization of services: although disadvantaged groups have equal access to treatments of non-discretionary effectiveness, they hardly use innovative services and are more vulnerable in receiving unnecessary treatments.

[Differences in in-hospital mortality in patients treated with aortocoronary bypass for cardiopathic ischemia, Rome 1996]. / Differenze di mortalità intraospedaliera in pazienti sottoposti a bypass aortocoronarico per cardiopatia ischemica, Roma 1996.

Data from Health Information Systems (HIS) have been used in recent years to evaluate effectiveness and quality of care. We analyzed in-hospital mortality occurring within 30 days following operation among 1984 patients (age > or = 35 yrs, males 84%) who underwent Coronary Artery Bypass Graft (CABG) surgery in seven hospitals in Rome in 1996. Data were extracted from the Lazio HIS run by the Regional Health Authority. The HIS database includes up to four diagnoses and surgical procedures (ICD-9); the following variables were considered a priori risk factors: type of ischemic disease, comorbidities, and others surgical interventions during the same admission. Logistic regression was performed in order to evaluate the association between hospital and risk of mortality after adjusting for potential confounders (ORs and 95% CI). The overall in-hospital mortality was 4.7% (ranged from 0.0 to 14.7%). Predictors of outcome included: older age, acute myocardial infarction, chronic myocardial ischemia, other heart diseases, chronic renal diseases, peripheral vascular diseases, other heart and vascular interventions. Statistically significant variability in mortality was observed across hospitals; taking hospital A as reference, hospitals D and E showed the highest risks (OR = 6.36 and OR = 3.12, respectively). We conclude that the observed differences in mortality rates among hospitals cannot be explained by differences in case mix, nor by varying coding styles. They are likely to reflect differences in currently unknown aspects of patient care.

Effect of protein synthesis inhibition before or during in vitro maturation on subsequent development of bovine oocytes.

The overall objective of this study was to assess the effect of maintaining meiotic arrest in bovine oocytes in vitro on developmental competence. In Experiment 1 the effect of inhibition of meiotic resumption using cycloheximide (CX), on subsequent was examined. Immature cumulus oocyte complexes (COCs, n = 804) were cultured in the absence (24 h) or presence of CX for 6, 12, 18 or 24 h. The control was inseminated 24 h later, while CX-treated oocytes were cultured for a further 24 h before insemination. In Experiment 2 the effect of exposing the oocyte (n = 1239) during meiotic arrest to putative stimulatory substances (pFSH and FCS) was examined. In Experiment 3, to study the importance of protein synthesis during maturation, synthesis was blocked for a 6-h period at various times (6, 12, 18 h) after start of culture (n = 1117). In Experiment 1, there was no difference in cleavage rate between treatments. However, the percentage of 5 to 8 cell embryos at 72 h post insemination was significantly lower after CX treatment (64 vs 42 to 51%; P < 0.05). This was reflected in a lower rate of blastocysts at Day 6 (9 to 15 vs 31%, P < 0.002). While the blastocyst rate at Day 8 was lower in CX-treated oocytes, the effect was only significant when CX was present for longer than 12 h. A marked decrease in development was noted following inhibition for 18 h or more compared with the control (17 to 19 vs 40%; P < 0.0002). In Experiment 2, addition of either FSH or FCS to oocytes in the presence of CX had no effect on any of the parameters studied, even though there was a positive effect in control oocytes. In Experiment 3, treatment with CX after the oocytes had matured for varying periods resulted in decreased blastocyst rates at Days 6 and 8 of culture. The most significant drop in development occurred when oocytes were cultured for 12 h before exposure to CX (15 vs 40%; P < 0.0001). In conclusion, CX-blocked oocytes retained their developmental competence, although final blastocyst yields were reduced.

Inhibition of in vitro keratinization of chick embryo skin cultured with hepatectomized rat serum.

In the present study organ cultures of 6 day-old chick embryo matatarsal skin were used to determine the effect of hepatectomized rat serum in modulating epithelial differentiation. Six day-old chick embryo skin, maintained in organ culture for 6-7 days with a medium containing adult rat serum, was seem to undergo differentiation and keratinization faster then in vivo. Epidermis cultured for 6-7 days with a medium containing partially hepatectomized rat serum does not differentiate and the squamous layer is absent. Studies with 3H-cystine show a sharp decrease in the labelled amino-acids incorporation in the cultures added with serum obtained after partial hepatectomy.

[Action of human serum on differentiation of skin in vitro. Morphological data and study of the incorporation of labeled amino acids]. / Azione del siero umano sul differenziamento della cute in vitro. Dati morfologici e studio dell'incorporazione di aminoacidi marcati.

Epithelial-mesodermal tissue interactions have been shown to be required for normal cytodifferentiation of chick embryo skin. Six-day limb skin does not develop in a protein free chemically defined medium, but keratinization has been observed in medium containing chicken serum. In the present study the authors show that the addition of human serum may stimulate the in vitro differentiation of explants of six-day chick embryo skin. Human serum is able to support skin keratinization and this finding has been confirmed by histological and histochemical criteria. Synthesis of proteins in tissue cultures supplemented with human serum has been studied by use of labeled amino acids such as H3-Leucine and C14-Cystine. These incorporation studies show the existence of macromolecular factors in human serum which may be responsible for the observed skin differentiation.

[Further research on the differentiation in vitro of chick-embryo skin in the presence of histones]. / Ulteriori ricerche sul differenziamento in vitro della pelle di embrione di pollo in fresenza di istoni.

In the present study the authors have carried out further researches on the differentiation of six day limb skin from chick embryo cultured "in vitro" in a complete medium supplemented with histones. When histones were added to the medium in the first two days "in vitro", epidermal keratinization was not observed. However the addition of histones after four days "in vitro" did not interfere with epidermal differentiation.

[Differentiation in vitro of chick-embryo skin in presence of histones. Analysis of protein synthesis in toto and of keratin in particular, with the use of labeled precursors]. / Studio del differenziamento in vitro della pelle di embrione di pollo in presenza di istoni. Analisi della sintesi proteica in toto e della cheratina in par ticolare con l'uso di precursori marcati.

Six-day limb skin from a chick embryo was cultured in vitro for seven days in a complete medium either supplemented or not with histones. At the end of the incubation period, the chick embryo skin cultured in the absence of histones was found to undergo keratinization, the converse being true for the limbs cultured in the presence of histones. In the latter, when H3-leucine and C14-cystine were added to the medium, a sharp decrease in the labeled amino acid incorporation was found.