The epidemiologic Health Impact Assessment (eHIA) process is receiving growing attention in Italy. In the context of such an approach, the present paper has three objectives: to review the ...computational aspects of eHIA for stressing strengths and weaknesses of methods and formulas; to discuss which rate at baseline could be used for the estimation of attributable cases; how to use the results of eHIA to make decisions regarding the realization of industrial projects.
Using a linear formulation of the relationship between exposure and disease occurrence: a) formulas have been derived to compute attributable cases (AC) using both Relative Risk (RR) and Excess Risk (ER) approaches; b) a discussion is made of the use as baseline rate of the rate that is caused by all the risk factors for a particular disease and a suggestion is made to use the rate that is caused simply by the risk factors that are under evaluation; c) under assumptions and approximations that must be validated in any specific situation, formulas are derived to compute Incremental Lifetime Cumulative Risk (ILCR), an indicator that can be used to compare the results coming from the eHIA approach with the levels of action used by USEPA and others (10-6, 10-5, 10-4). -Conclusion: In this paper, the methodology and the formulas commonly used in eHIA have been enlarged to consider the case in which the baseline rate is equal to zero, suggesting to use Excess Risk (ER) estimates instead of Relative Risk (RR) estimates. Using different baseline rates produces very different estimates of AC, and work needs to be done on this topic. Lastly, due to assumptions, approximations, and uncertainty of eHIA computations, prudence and caution should be exercised in using eHIA results in decision making, particularly if hard decisions have to be made.
Background.
The evidence supporting the use of trastuzumab (T) in a metastatic setting comes from studies that included (almost) only patients who never received prior T. We investigated the ...effectiveness of T as first‐line therapy for metastatic breast cancer (mBC) in women previously treated with T in the adjuvant setting.
Materials and Methods.
By using record linkage of five administrative health care databases of Lombardy, Italy, we identified 2,046 women treated with T for early breast cancer (eBC) in 2006–2009, 96 of whom developed a metastasis and were retreated with T in first‐line treatment for mBC (treatment group). We compared the overall survival (OS) of these women with that of 197 women treated with T in first‐line treatment for mBC, who were treated with therapies other than T for early disease (control group). We computed Kaplan‐Meier 2‐year OS and used a proportional hazard model to estimate the multivariate hazard ratio (HR) of death in the intervention group compared with the control group, adjusted by age, use of endocrine therapy, and site of metastasis.
Results.
Two‐year OS was 60.0% in the treatment group and 59.5% in the control group. The adjusted HR of death in the treatment group compared with the control group was 0.79 (95% confidence interval, 0.50–1.26).
Conclusion.
Our data provide convincing evidence that the outcome of women receiving first‐line T treatment for mBC after T failure in the adjuvant setting is comparable to that of women not receiving T for eBC. These data are of specific interest, given the unavailability of data from randomized clinical trials.
The effectiveness of trastuzumab (T) as first‐line therapy for metastatic breast cancer (mBC) in women previously treated with T in the adjuvant setting was investigated. The outcome of women receiving first‐line T treatment for mBC after T failure in the adjuvant setting is comparable to that of women not receiving T for early breast cancer.
The increase in the number of patients with CKD starting dialysis treatment has become a major health problem in recent years. Osteoporosis is a typical feature of advanced age, which, in the ...dialysis population, is almost always accompanied by uremic osteodystrophy (CKD-MBD). These two factors are involved in the pathogenesis of fractures, which represent an important risk factor for the outcome of patients. The real consistency of fractures in CKD patients on kidney replacement therapy (KRT) requiring hospitalization in the Lombardy region (over 9,000,000 inhabitants) was analyzed using data from the regional administrative databases in the years 2011–2012. Among 8109 prevalent patients, 251 (45.8% women), with fractures after 1 January 2011, entered the analysis. A follow-up of two years (2011–2012) was considered to evaluate the incidence of more frequent fractures (femur, pelvis, hip, and spine) using ICD-9-CM codes. The most frequent sites of fractures were the femur (68.5%), hip and pelvis (47.4%), and vertebrae (12%). The patients on hemodialysis (HD) had more events than PD (3.3% vs. 1.4%; p = 0.03), while patients undergoing kidney transplantation (KTx) had a significantly lower percentage of fractures (0.6% vs. 3.3%; p < 0.001). Observed mortality was very high: the estimated gross mortality rate for any cause was 25.9% at 90 days and 34.7% at 180 days. Diabetes, peripheral vasculopathy, and heart failure were associated with a numerical increase in fractures, although this was not significant. Proton pump inhibitor drugs (PPI), vitamin K antagonists, and diphosphonates were more frequently associated with fracture occurrence. The average total cost of fractured patients was 11.4% higher than that of non-fractured patients. On multivariate analysis, age >65 years, female gender, PPI therapy, and cerebrovascular disease were found to be strongly associated with fractures in dialysis patients, whereas undergoing renal transplantation presented a reduced risk.
Administrative databases are widely available and have been extensively used to provide estimates of chronic disease prevalence for the purpose of surveillance of both geographical and temporal ...trends. There are, however, other sources of data available, such as medical records from primary care and national surveys. In this paper we compare disease prevalence estimates obtained from these three different data sources.
Data from general practitioners (GP) and administrative transactions for health services were collected from five Italian regions (Veneto, Emilia Romagna, Tuscany, Marche and Sicily) belonging to all the three macroareas of the country (North, Center, South). Crude prevalence estimates were calculated by data source and region for diabetes, ischaemic heart disease, heart failure and chronic obstructive pulmonary disease (COPD). For diabetes and COPD, prevalence estimates were also obtained from a national health survey. When necessary, estimates were adjusted for completeness of data ascertainment.
Crude prevalence estimates of diabetes in administrative databases (range: from 4.8% to 7.1%) were lower than corresponding GP (6.2%-8.5%) and survey-based estimates (5.1%-7.5%). Geographical trends were similar in the three sources and estimates based on treatment were the same, while estimates adjusted for completeness of ascertainment (6.1%-8.8%) were slightly higher. For ischaemic heart disease administrative and GP data sources were fairly consistent, with prevalence ranging from 3.7% to 4.7% and from 3.3% to 4.9%, respectively. In the case of heart failure administrative estimates were consistently higher than GPs' estimates in all five regions, the highest difference being 1.4% vs 1.1%. For COPD the estimates from administrative data, ranging from 3.1% to 5.2%, fell into the confidence interval of the Survey estimates in four regions, but failed to detect the higher prevalence in the most Southern region (4.0% in administrative data vs 6.8% in survey data). The prevalence estimates for COPD from GP data were consistently higher than the corresponding estimates from the other two sources.
This study supports the use of data from Italian administrative databases to estimate geographic differences in population prevalence of ischaemic heart disease, treated diabetes, diabetes mellitus and heart failure. The algorithm for COPD used in this study requires further refinement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients on dialysis often have secondary hyperparathyroidism (SHPT), a disorder associated with renal osteodystrophy, progressive vascular calcification, cardiovascular disease, and death. The ...objective of this retrospective observational study was to evaluate, in dialysis patients with SHPT, the impact of different levels of adherence to cinacalcet therapy on hospitalisations and direct healthcare costs charged to the Lombardy Regional Health Service (Italy).
Data recorded in the administrative databases on all citizens undergoing dialysis between 1 January 2011 and 31 December 2011 were selected. For the aim of this study, patients with SHPT already on dialysis in the first 6 months of 2009 who had been treated with cinacalcet for at least 365 days were selected and retrospectively analysed through to end of 2012. Healthcare resource utilisation, cinacalcet adherence, and costs for medication, hospitalisations, and diagnostic/therapeutic procedures were estimated.
A total of 994 patients were identified (mean age 63.0 years, females 43.5%). The first patient tertile had an adherence to cinacalcet of <64.1%, whereas the third had an adherence of over 91.5%. Patients in the third adherence tertile experienced fewer all-causes hospitalisations than those in the first tertile (-19.2%;
=0.01423), fractures (-37.1%;
=0.59422), cardiovascular disease (-23.8%;
=0.04025), and sepsis (-32.3%;
=0.01386). The increase in costs for cinacalcet-adherent patients is almost completely offset by the reduction in costs for hospitalisations.
The results of the analysis suggest that there may be some correlation between a high level of cinacalcet adherence and a decrease in hospitalisations.
The aim of this study was to describe the clinical use of bevacizumab in Lombardy (9.5 million inhabitants), Italy, during 2006–2007 in patients with metastatic colorectal cancer (mCRC) to evaluate ...compliance with the Italian Medicine Agency (AIFA) indications, the incidence of adverse events, and the survival rate.
We performed computerized record linkage among three different Lombardy health care databases: File F registry, Regional discharge database, and Registry Office records. Patients were classified into approved and off‐label uses according to the AIFA indications.
Treatment with bevacizumab was administered to 780 patients, of whom 81.7% (n = 637) had mCRC. Among these, 37.8% (n = 241) of patients received the drug in observance of AIFA indications. Overall, ∼10% of patients had serious treatment‐related toxicities (fistula, 3.5%; venous thromboembolism, 2.8%; hemorrhage, 1.9%; intestinal perforation and arterial thromboembolism, <1%). The 1‐year survival rate was 74.3% and the 2‐year survival rate was 39.2%. The median survival time was 20.5 months, and there were no meaningful differences between gender and age groups.
There was a gap between the bevacizumab approved indication and clinical practice pattern: overall, less than one half of the patients received bevacizumab in observance with the regulatory indication. The main reason for nonadherence to the indication was use as a second‐line or advanced line of therapy. The incidence of serious adverse events and the survival rates of mCRC patients were similar to those reported in clinical trials.
摘要
本研究的目的是，通过回顾2006‐2007年贝伐珠单抗在意大利 Lombardy 地区（950万居民）用于转移性结直肠癌（ mCRC ）患者的临床应用数据，评估其在意大利药品局（ AIFA ）所规定适应症的符合性、不良事件的发生率以及生存率。
回顾性分析 Lombardy 地区三个不同的医疗保健数据库的计算机链接记录，包括 File F 登记库、当地出院病人数据库以及登记办公室记录数据库。根据 AIFA 规定的适应症将患者分为两类，即适应症内使用与适应症外使用。
共有 780 例患者接受了贝伐珠单抗治疗，其中81.7%（ n=637）为 mCRC 。在这些患者中，有37.8%（n =241）用药符合 AIFA 规定的适应症。约10%的患者出现严重治疗相关毒性（瘘管 3.5%；静脉血栓栓塞2.8%；出血1.9%；肠穿孔与动脉血栓栓塞<1%）。1年生存率与2年生存率分别为74.3%和39.2%。中位生存期为20.5个月，不同性别与年龄组间无显著差异。
已批准的贝伐珠单抗适应症与临床实践间存在差异：总体而言，只有不到一半的患者使用贝伐珠单抗是符合规定适应症的。不符合适应症的主要原因是将贝伐珠单抗用作二线或更后线的治疗。 mCRC 患者中严重不良事件的发生率及生存率与已报道的临床研究结果相近。
Compliance with the Italian Medicine Agency indications for bevacizumab was examined in Lombardy (9.5 million inhabitants), Italy, during 2006–2007 in patients with metastatic colorectal cancer using computerized databases. Less than one half of the patients received bevacizumab in observance with the regulatory indication. Incidence of major adverse events and median survival were comparable to those reported in clinical trials.
Pleural mesothelioma (PM) is a rare, highly lethal tumor. A definite consensus on its management has yet to be established.
To assess management, overall survival (OS), and their predictors in a ...cohort of patients from Lombardy, the largest Italian region (about 10 million inhabitants).
Through a record linkage between Lombardy health care administrative databases, we identified patients diagnosed with PM in 2006-2011 without history of cancer, evaluating their management. OS from PM diagnosis was estimated using the Kaplan-Meier method. Predictors of OS and of treatment were assessed using Cox regression models with time-dependent covariates when appropriate.
Out of 1,326 patients, 754 (56.9%) received treatment for PM: 205 (15.5%) underwent surgery, and 696 (52.5%) used chemotherapy. Surgery was spread across several hospitals, and most patients diagnosed in nonspecialized centers (70%) underwent surgery in the same centers. Age at diagnosis was a strong inverse determinant of surgery. Determinants of receiving chemotherapy were younger age, a more recent first diagnosis, and first diagnosis in a specialized center. OS was 45.4% at 1 year, 24.8% at 2 years, and 9.6% at 5 years (median 11 months). OS decreased with age, and was higher for those who underwent surgery, but not for those treated with chemotherapy.
Management of PM varied widely in clinical practice, and significant predictors of treatment were younger age and recent diagnosis, though a high proportion of patients were not treated. Patients were treated in various hospitals, indicating the importance of concentrating serious rare neoplasms in Comprehensive Cancer Centers (as recognized by the Italian Health Ministry).
The article discusses a recent study on mortality attributable to COVID-19 in Italy and the need for further analysis. The study used a reliable methodology to estimate excess deaths due to the ...pandemic. However, there are still questions about the specific effects of COVID-19 compared to other factors, such as delayed or missing access to treatment for other illnesses. Analyzing the time course of excess deaths could reveal such effects. There are also open questions about how COVID-19 deaths are classified and reported, which could lead to over or under-diagnosing cases. The article notes that occupational physicians have played an important role in preventing the spread of COVID-19 among workers. A recent study found that personal protective equipment (PPE), particularly masks, effectively reduced the risk of infection among healthcare workers. However, it is still unclear whether Occupational Medicine should incorporate infectious diseases as a major concern or return to its historically agnostic attitude toward communicable diseases. More data on mortality from specific diseases will be needed for further analysis and understanding of the pandemic's effects on mortality rates in Italy.
In a previous paper on acceleration of failure time we highlighted the difficulties of the application to the case of mesothelioma of the methodology proposed by Berry. In this contribution we ...elaborate further on the concept of anticipation/acceleration, taking into account the content of the III Italian Consensus Document.
We analyzed the ways in which the concept of anticipation/acceleration has been proposed and interpreted in the III Consensus Document.
We show that the concept of anticipation of the III Consensus Document has to do with incidence (frequency) in a population (and not with acceleration of the pathological process in an individual case), and is a measure which is alternative to other measures of frequency effects. In addition, we show that the same epidemiological result is compatible with causal models where no cases, all the cases, or some of the cases are anticipated.
This paper suggests that the concept of anticipation measurable through epidemiologic data has to do exclusively with the anticipation of a frequency indicator (more occurrencies and anticipated occurrencies are indistinguishable and alternative concepts) but not with the acceleration of the biological process in individual cases. In causal terms, without a biological support it is not possible to infer from the epidemiologic results if a causal model is in action with no, all, or some of cases anticipated.
The early effects of 2, 3, 7, 8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was ...the only effect linked with sufficient certainty to dioxin exposure. The possible longterm consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.
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