Application of failure mode and effect analysis in an assisted reproduction technology laboratory.

Assisted reproduction technology laboratories have a very high degree of complexity. Mismatches of gametes or embryos can occur, with catastrophic consequences for patients. To minimize the risk of error, a multi-institutional working group applied failure mode and effects analysis (FMEA) to each critical activity/step as a method of risk assessment. This analysis led to the identification of the potential failure modes, together with their causes and effects, using the risk priority number (RPN) scoring system. In total, 11 individual steps and 68 different potential failure modes were identified. The highest ranked failure modes, with an RPN score of 25, encompassed 17 failures and pertained to "patient mismatch" and "biological sample mismatch". The maximum reduction in risk, with RPN reduced from 25 to 5, was mostly related to the introduction of witnessing. The critical failure modes in sample processing were improved by 50% in the RPN by focusing on staff training. Three indicators of FMEA success, based on technical skill, competence and traceability, have been evaluated after FMEA implementation. Witnessing by a second human operator should be introduced in the laboratory to avoid sample mix-ups. These findings confirm that FMEA can effectively reduce errors in assisted reproduction technology laboratories.

Fatty liver index and mortality: the Cremona study in the 15th year of follow-up.

UNLABELLED: A fatty liver, which is a common feature in insulin-resistant states, can lead to chronic liver disease. It has been hypothesized that a fatty liver can also increase the rates of non-hepatic-related morbidity and mortality. Therefore, we wanted to determine whether the fatty liver index (FLI), a surrogate marker and a validated algorithm derived from the serum triglyceride level, body mass index, waist circumference, and γ-glutamyltransferase level, was associated with the prognosis in a population study. The 15-year all-cause, hepatic-related, cardiovascular disease (CVD), and cancer mortality rates were obtained through the Regional Health Registry in 2011 for 2074 Caucasian middle-aged individuals in the Cremona study, a population study examining the prevalence of diabetes mellitus in Italy. During the 15-year observation period, 495 deaths were registered: 34 were hepatic-related, 221 were CVD-related, 180 were cancer-related, and 60 were attributed to other causes. FLI was independently associated with the hepatic-related deaths (hazard ratio = 1.04, 95% confidence interval = 1.02-1.05, P < 0.0001). Age, sex, FLI, cigarette smoking, and diabetes were independently associated with all-cause mortality. Age, sex, FLI, systolic blood pressure, and fibrinogen were independently associated with CVD mortality; meanwhile, age, sex, FLI, and smoking were independently associated with cancer mortality. FLI correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), a surrogate marker of insulin resistance (Spearman's ρ = 0.57, P < 0.0001), and when HOMA-IR was included in the multivariate analyses, FLI retained its association with hepatic-related mortality but not with all-cause, CVD, and cancer-related mortality. CONCLUSION: FLI is independently associated with hepatic-related mortality. It is also associated with all-cause, CVD, and cancer mortality rates, but these associations appear to be tightly interconnected with the risk conferred by the correlated insulin-resistant state.

Risk Management in healthcare: results from a national-level survey and scientometric analysis in Italy.

Risk management in healthcare, intended as all processes employed to detect, monitor, assess, mitigate, and prevent risks in healthcare facilities and safeguard patient safety, is a crucial component of Italy' National Health Service. Aim of the current study is to assess the role and progress of  research and training, in the field of Risk Management. We carried out a scientometric analysis to quantify and describe scientific outputs on Risk Management at the global and national level, over the last forty years; in addiction, we conducted a national-level cross-sectional survey to systematically retrieve and assess research and training activities within Italian postgraduate medical programmes in Hygiene and Preventive Medicine.   We report increasing scientific production on Risk Management-related topics from 1980 to 2017 at the global level (12% annual increase rate). Clinical Trials and Systematic reviews/meta-analysis make up for respectively 5% and 6% of global scientific output. Italy ranks 4th for scientific production, after USA, UK and Germany. 88% of Italian postgraduate medical programmes in Hygiene and Preventive medicine research on Risk Management, 42% through international collaborations. The main research themes are Healthcare-Associated Infections (HAIs) (97%), analysis of organizational models for safety in healthcare (62%), while training is focused on internships (87%) and academic lectures (73%). While research provides the evidence required to plan, implement and monitor effective interventions in healthcare risk management, training allows its dissemination in a synergic action to promote the value of patient safety and quality of care.

Fasting plasma leptin, tumor necrosis factor-alpha receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women: impact on cardiovascular mortality.

OBJECTIVE: Leptin and tumor necrosis factor (TNF)-alpha are associated with insulin resistance and cardiovascular disease. In vitro studies suggested that these effects may be mediated via overproduction of monocyte chemoattracting protein (MCP)-1/CCL2, which is a chemokine involved in the pathogenesis of atherosclerosis. RESEARCH DESIGN AND METHODS: In this study, fasting plasma leptin, soluble TNF-alpha receptor 2 (TNF-alpha-R2), and MCP-1/CCL2 concentrations were measured in 207 middle-aged women (age 61 +/- 12 years, BMI 30.1 +/- 6.6 kg/m(2)), including 53 patients with type 2 diabetes, 42 with impaired glucose tolerance, and 112 with normal glucose tolerance, to assess cross-sectionally their relationship with markers of atherosclerosis and, longitudinally over 7 years, whether their circulating levels were associated with cardiovascular disease (CVD) mortality. RESULTS: At baseline, leptin and TNF-alpha-R2 were not different among groups; meanwhile, MCP-1/CCL2 was increased in type 2 diabetes (P < 0.05). All showed significant associations with biochemical risk markers of atherosclerosis. In a univariate analysis, age, fasting insulin, leptin, and MCP-1/CCL2 were associated with CVD mortality at 7 years. When a multivariate analysis was performed, only age, leptin, and insulin retained an independent association with CVD mortality, with leptin showing a protective effect (hazard ratio 0.88; P < 0.02). CONCLUSIONS: In middle-aged women, MCP-1/CCL2, leptin, and TNF-alpha-R2 were all related to biochemical risk markers of atherosclerosis. MCP-1/CCL2 concentration was the only one to be increased in type 2 diabetes with respect to nondiabetic women and the only one to be associated with increased risk of CVD mortality after a 7-year follow-up period in the univariate analysis. In the multivariate analysis, neither MCP-1/CCL2 nor TNF-alpha-R2 was associated with CVD mortality, and inspection of the data showed that leptin, in both the univariate and multivariate analysis, was associated with a protective effect.

The costs of type 2 diabetes mellitus in Italy: a CODE-2 sub-study.

AIM: To estimate the direct, indirect, and intangible costs associated with type 2 diabetes mellitus in Italy in 1998. To evaluate the economic impact of diabetic complications, and to investigate drug treatment patterns and associated costs in patients with type 2 diabetes. METHODS: The Italian arm of an international study (COsts of Diabetes in Europe--Type 2 [CODE-2], a descriptive, cross-sectional survey) was set up to collect information retrospectively by means of questionnaires from a sample of 1263 patients. Resource use was measured in monetary terms using a set of costs and tariffs. Intangible costs were estimated using the EuroQol questionnaire. RESULTS: The average yearly cost for medical resources for a patient with type 2 diabetes was 2991 Euro, whereas the estimated cost for the whole population with type 2 diabetes was about 5170 million Euro. This corresponds to 6.65% of the total healthcare expenditure (public and private) in Italy. Of direct costs, 29% was spent for the treatment of diabetes and 39% for the treatment of diabetic complications; while the remaining 32% was spent for healthcare not related to diabetes. Quality of life score in patients with type 2 diabetes (EuroQoL overall average score) was 0.68. CONCLUSIONS: Type 2 diabetes has a high cost to society. The major cost component is due to the care of diabetic complications, not to the treatment of the illness itself; in particular, drug costs represent a relatively small proportion of such treatment cost.

Insulin resistance/hyperinsulinemia and cancer mortality: the Cremona study at the 15th year of follow-up.

Type 2 diabetes is associated with risk of cancer. Hyperinsulinemia and insulin resistance may be the link with cancer, but whether this is independent of the diabetes status, obesity/visceral obesity and metabolic syndrome is uncertain and the present study wanted to address this issue. Fifteen-year all-cause, CVD and cancer mortality data were obtained through the Regional Health Registry in 2,011 out of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes mellitus in Italy in which anthropometric and metabolic characteristics were collected. During the 15-year observation period, 495 deaths were registered: 221 CVD related and 180 cancer related. Age and sex were independently associated with all-cause, cancer and CVD mortality rates. Age- and sex-adjusted analysis showed that HOMA-IR, cigarette smoking and diabetes were independently associated with all-cause mortality; HOMA-IR, systolic blood pressure and fibrinogen were independently associated with CVD mortality; HOMA-IR and smoking habit were independently associated with cancer mortality. Individuals in the highest quintile of serum insulin had a 62% higher risk of cancer mortality (HR = 1.62 95% CI: 1.19-2.20; P < 0.0022) and 161% higher risk of gastrointestinal cancer mortality (HR = 2.61 95% CI: 1.73-3.94; P < 0.0001). Age- and sex-adjusted analysis showed that hyperinsulinemia/insulin resistance is associated with cancer mortality independently of diabetes, obesity/visceral obesity and the metabolic syndrome.

Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: the Cremona Study.

OBJECTIVE: Some obese individuals have normal insulin sensitivity. It is controversial whether this phenotype is associated with increased all-cause mortality risk. RESEARCH DESIGN AND METHODS: Fifteen-year all-cause mortality data were obtained through the Regional Health Registry for 2,011 of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes in Italy. Individuals were divided in four categories according to BMI (nonobese: <30 kg/m²; obese: ≥30 kg/m²) and estimated insulin resistance (insulin sensitive: homeostasis model assessment of insulin resistance <2.5; insulin resistant ≥2.5). RESULTS: Obese insulin-sensitive subjects represented 11% (95% CI 8.1-14.5) of the obese population. This phenotype had similar BMI but lower waist circumference, blood pressure, fasting glucose, triglycerides, and fibrinogen and higher HDL cholesterol than obese insulin-resistant subjects. In the 15-year follow-up, 495 deaths (cardiovascular disease [CVD]: n = 221; cancer: n = 180) occurred. All-cause mortality adjusted for age and sex was higher in the obese insulin-resistant subjects (hazard ratio 1.40 [95% CI 1.08-1.81], P = 0.01) but not in the obese insulin-sensitive subjects (0.99 [0.46-2.11], P = 0.97) when compared with nonobese insulin-sensitive subjects. Also, mortality for CVD and cancer was higher in the obese insulin-resistant subjects but not in the obese insulin-sensitive subjects when compared with nonobese insulin-sensitive subjects. CONCLUSIONS: In contrast to obese insulin-resistant subjects, metabolically healthy obese individuals are less common than previously thought and do not show increased all-cause, cancer, and CVD mortality risks in a 15-year follow-up study.

Diagnostic sensitivity of thyroid autoantibodies assessed in a population-based, cross-sectional study in adults.

The aim of this study was to estimate the diagnostic sensitivity of thyroid autoantibodies in individuals with a case-mix of subjects with thyroid disease representing that of the general population. We measured thyroid microsome (TMA), thyroid peroxidase (TPO), thyroglobulin (TGA) and thyroid-stimulating hormone (TSH) receptor (TRA) autoantibodies in subjects in the bottom (hyperthyroid end) and top (hypothyroid end) four percentiles of the TSH distribution from among participants in a population-based survey of individuals aged ≥40 years (the Cremona Study). TMA and TPO were the most sensitive autoantibodies in subjects in both the bottom percentiles (19.8% and 18.5%, respectively) and the top percentiles (51.2% and 53.8%, respectively) of the TSH distribution. TMA and TPO showed good agreement (kappa statistics 87.8%, 95% CI 80.1-95.5%) at both ends of the TSH distribution. TGA were the next most sensitive marker, although seldom detected if TMA or TPO were not present. TRA were detected only at the extremes of the TSH distribution (1st percentile, 31.8%; 100th percentile, 25.0%). We conclude that, among a case-mix of individuals with thyroid disease representing that of the general population, TMA and TPO are the most sensitive markers of thyroid disease. TGA only marginally increased the diagnostic sensitivity of TMA and TPO. TRA are sensitive markers of thyroid disease only at the extremes of thyroid function.

Association between plasma monocyte chemoattractant protein-1 concentration and cardiovascular disease mortality in middle-aged diabetic and nondiabetic individuals.

OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine involved into the pathogenesis of atherosclerosis and has prognostic value in the acute and chronic phases in patients with acute coronary syndromes. RESEARCH DESIGN AND METHODS: MCP-1/CCL2 concentration was measured in plasma fractions of 363 middle-aged overweight/obese individuals (aged 61 +/- 12 years, BMI 30.1 +/- 6.6 kg/m(2), 15% with type 2 diabetes, and 12% with impaired glucose tolerance) of a population survey carried out in 1990-1991 in Lombardy, Italy (Cremona Study), and cardiovascular disease (CVD) mortality was assessed in 2006 through Regional Health Registry files. RESULTS: At baseline MCP-1/CCL2 was increased in individuals with type 2 diabetes (P < 0.05) and showed significant correlations with biochemical risk markers of atherosclerosis. After 15 years, among the 363 subjects, there were 82 deaths due to CVD. In univariate analysis age, sex, fasting glucose and insulin, fibrinogen, glucose tolerance status, smoking habit, and MCP-1/CCL2 were associated with CVD mortality. Age, sex, fasting serum glucose, MCP-1/CCL2, and smoking habit maintained an independent association with CVD mortality in multiple regression analysis. In a subgroup of 113 subjects in whom data for C-reactive protein (CRP) were available, its level was not predictive of CVD mortality. CONCLUSIONS: In middle-aged overweight/obese individuals MCP-1/CCL2 was independently associated with CVD mortality. Further studies will be necessary to establish its role as a surrogate biomarker and as a potential therapeutic target.