Learning from the COVID-19 pandemic in Italy to advance multi-hazard disaster risk management.

COVID-19 challenged all national emergency management systems worldwide overlapping with other natural hazards. We framed a 'parallel phases' Disaster Risk Management (DRM) model to overcome the limitations of the existing models when dealing with complex multi-hazard risk conditions. We supported the limitations analysing Italian Red Cross data on past and ongoing emergencies including COVID-19 and we outlined three guidelines for advancing multi-hazard DRM: (i) exploiting the low emergency intensity of slow-onset hazards for preparedness actions; (ii) increasing the internal resources and making them available for international support; (iii) implementing multi-hazard seasonal impact-based forecasts to foster the planning of anticipatory actions.

Prevalence of vertebral fractures, vascular calcifications, and mortality in warfarin treated hemodialysis patients.

Warfarin inhibits vitamin-K dependent proteins involved in bone mineralization and the prevention of vascular calcification (bone Gla protein BGP, matrix Gla protein MGP). In this multicenter, cross-sectional study with 3-year follow-up, data from 387 patients on hemodialysis for ≥1 year at 18 dialysis units were analyzed. Patients on warfarin treatment for > 1 year (11.9% of the population) were compared with the remaining cohort for vertebral fractures, vascular calcifications and mortality. Vertebral fractures and vascular calcifications were sought in L-L vertebral X-rays (D5 to L4). Compared with controls, warfarin-treated male patients had more vertebral fractures (77.8 vs. 57.7%, p<0.04), but not females (42.1% vs. 48.4%, p=0.6); total BGP was significantly reduced (82.35 vs. 202 µg/L, p<0.0001), with lower levels in treated men (69.5 vs. women 117.0 µg/L, p=0.03). In multivariate logistic regression analyses, the use of warfarin was associated with increased odds of aortic (OR 2.58, p<0.001) and iliac calcifications (OR 2.86, p<0.001); identified confounders were age, atrial fibrillation, angina, PPI use and total BGP. Seventy-seven patients died during a 2.7±0.5 year follow-up. In univariate Cox regression analysis, patients on warfarin had a higher risk of all-cause mortality (HR 2.42, 95% CI 1.42-4.16, p=0.001) when compared with those untreated and data adjustment for confounders attenuated but confirmed the significant warfarin-mortality link (HR: 1.97, 95% CI: 1.02-3.84, P=0.046). In hemodialysis patients, additional studies are warranted to verify the risk/benefit ratio of warfarin, which appears to be associated with significant morbidity and increased mortality.

The relationship between the Spine Deformity Index, biochemical parameters of bone metabolism and vascular calcifications: results from the Epidemiological VERtebral FRACtures iTalian Study (EVERFRACT) in dialysis patients.

BACKGROUND: The Spine Deformity Index (SDI) is a measure of vertebral fractures (VFs), providing information on both their number and severity. METHODS: We evaluated the relationships between SDI and clinical, biochemical and arterial calcification parameters in 387 hemodialysis (HD) patients. VFs, assessed by quantitative vertebral morphometry, and vascular calcifications were identified in the same lateral spinal X-ray. To improve the detection of fracture severity, we created a corrected SDI (c-SDI), by dividing SDI for the number of VFs. We assessed routine biochemistry, bone-Gla-protein (BGP), undercaboxylated BGP (ucBGP), and matrix-Gla-protein (MGP). RESULTS: VFs prevalence was 55.3%. HD patients with a SDI >1 were more frequently males (p<0.05), and had lower BGP (p<0.01). Patients with a c-SDI >1 had higher LDL-cholesterol (p<0.05) and lower ucBGP (p<0.05) and MGP (p<0.05). Calcifications of the abdominal aorta (AAoC) were more frequent in patients with SDI >1 (p<0.05) and with c-SDI >1 (p<0.05). Multivariate logistic regression showed that male sex (OR 1.86, CI 1.20-2.91), age (OR 1.03, CI 1.01-1.05) and albumin ≥3.5 g/dL (OR 0.54, CI 0.31-0.93) were predictors of a SDI >1. Age (OR 1.05, CI 1.03-1.07), LDL-cholesterol (OR 1.74, CI 1.04-2.92) and ucBGP (OR 0.35, CI 0.18-0.70) were associated with c-SDI >1. CONCLUSIONS: We conclude that the severity of VFs was associated with age, atherogenic factors and bone metabolism markers.

Long-term proton pump inhibitor use is associated with vascular calcification in chronic kidney disease: a cross-sectional study using propensity score analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are a class of drugs that is extensively used for common gastrointestinal disorders and often prescribed long-term for years. Long-term PPI treatment is associated with an increased risk of fractures in the general population. Several studies have suggested a relationship between vascular calcification, which is a predictor of cardiovascular morbidity and mortality, impaired bone metabolism and fractures. In dialysis patients, vascular calcifications are widespread and are connected to bone health. OBJECTIVE: The aim of this study was to assess the association between the use of PPIs and vascular calcifications involving the aorta and iliac arteries in haemodialysis patients. METHODS: Between November 2008 and November 2009, 387 patients receiving long-term dialysis treatment (≥1 year) were enrolled in a multicentre (18 Dialysis Units), cross-sectional study. Overall, 76.2 % of patients were receiving long-term PPI treatment. The main outcome measure was calcification of the aorta and iliac arteries in relation to PPI use. Standardized radiographs were sent to the coordinating centre for centralized evaluation in duplicate by two physicians who were blind to PPI status. RESULTS: Arterial calcifications were significantly more common in the PPI group (p < 0.01). Also, the rates of aortic and iliac calcifications considered separately were higher (+12.2 %, p = 0.0254; and +13.6 %, p = 0.0211, respectively). After correction for the propensity score, the odds ratios [ORs] (95 % CI) related to PPI use were aorta 1.89 (1.01-3.54), p = 0.048; iliac arteries 2.27 (1.31-3.92), p = 0.003; aorta and iliac arteries 2.59 (1.48-4.53), p = 0.008. The ORs (95 % CI) related to the association of warfarin + PPI were aorta 2.19 (0.95-5.00), p = 0.06; iliac arteries 2.90 (1.07-7.86), p = 0.036; aorta and iliac arteries 2.69 (1.03-6.96), p = 0.042. CONCLUSION: In haemodialysis patients, long-term treatment with PPIs, especially in the presence of warfarin treatment, is associated with vascular calcifications.

High prevalence of vertebral fractures assessed by quantitative morphometry in hemodialysis patients, strongly associated with vascular calcifications.

Few studies have provided information on the prevalence of vertebral fractures (VFs) and their risk factors in hemodialysis patients. A multicenter, cross-sectional, observational study was carried out to assess the prevalence of VFs and vascular calcifications (VCs) in 387 hemodialysis patients (mean age 64.2 ± 14.1 years, 63 % males) and in a control group of 51 osteoporotic subjects. Biochemical tests included 25(OH) vitamin D, bone Gla protein (total and undercarboxylated), and total matrix Gla protein. Vertebral quantitative morphometry was carried out centrally for the detection of VF, defined as reduction by ≥20 % of one of the vertebral body dimensions. In the same radiograph, aortic and iliac VC scores were calculated. Prevalence of VF was 55.3 % in hemodialysis patients and 51.0 % in the control group. Multivariate analysis disclosed that male gender (59.8 vs. 47.6 %, p = 0.02; OR = 1.78, 95 % CI 1.15-2.75) and age (mean ± SD 66.7 ± 13.1 vs. 61.0 ± 14.7 years, p < 0.001; OR = 1.03, 95 % CI 1.01-1.05) were significantly associated with VF. The prevalence of aortic VC was significantly higher in hemodialysis patients than in controls (80.6 vs. 68.4 %, p = 0.001). The factors with the strongest association with VC, apart from atrial fibrillation, were serum 25(OH)vitamin D levels below 29 ng/mL for aortic VC (OR = 1.85, 95 % CI 1.04-3.29) and VF both for aortic (OR = 1.77, 95 % CI 1.00-3.14) and iliac (OR = 1.96, 95 % CI 1.27-3.04) VC. In conclusion, the prevalence of VF, especially in males, and VC, in both genders, is high in hemodialysis patients. VF is associated with VC. Vitamin D deficiency is also associated with VC. Further longitudinal studies are warranted to investigate fractures in renal patients.

Vitamin K, vertebral fractures, vascular calcifications, and mortality: VItamin K Italian (VIKI) dialysis study.

Vitamin K (vitamin K1 or phylloquinone and vitamin K2, a series of menaquinones [MKs]) is involved in the production of bone and matrix amino acid γ-carboxy-glutamic acid (Gla) proteins, regulating bone and vascular calcification. Low vitamin K concentrations are associated with increased risks of fractures and vascular calcification, and frequent complications in hemodialysis patients. We carried out an observational study to establish the prevalence of vitamin K deficiency and to assess the relationship between vitamin K status, vertebral fractures, vascular calcification, and survival in 387 patients on hemodialysis for ≥1 year. We determined plasma levels of vitamin K compound, bone-Gla-protein, matrix-Gla-protein, and routine biochemistry. Vertebral fractures (reduction in vertebral body height by ≥20%) and aortic and iliac calcifications were also investigated in a spine (D(5) -L(4)) radiograph. Three-year patient survival was analyzed. Important proportions of patients had deficiency of MK7 (35.4%), vitamin K1 (23.5%), and MK4 (14.5%). A total of 55.3% of patients had vertebral fractures, 80.6% had abdominal aorta calcification, and 56.1% had iliac calcification. Vitamin K1 deficiency was the strongest predictor of vertebral fractures (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.38-6.26). MK4 deficiency was a predictor of aortic calcification (OR, 2.82; 95% CI, 1.14-7.01), whereas MK5 deficiency actually protected against it (OR, 0.38; 95% CI, 0.15-0.95). MK7 deficiency was a predictor of iliac calcification (OR, 1.64; 95% CI, 1.03-2.60). The presence of vertebral fractures was also a predictor of vascular calcifications (OR, 1.76; 95% CI, 1.00-3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, and cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients, pointing out a possible role of vitamin K in bone and vascular health. Based on our results, we suggest that the general population should also be studied for vitamin K deficiency as a possible cause of both vertebral fractures and vascular calcification.

Bleeding, vertebral fractures and vascular calcifications in patients treated with warfarin: hope for lower risks with alternative therapies.

Anticoagulant therapy in patients with atrial fibrillation requires careful evaluation because its benefits i.e. prevention of thromboembolism, must be greater than the risk of bleeding. Patients at higher risk of thrombosis are evaluated through specific scores, such as the CHA(2)DS(2)VASc, coupled with scoring systems for assessing bleeding risks, such as the HAS-BLED score. In addition to bleeding, other risks have been associated with the use of warfarin, including an increased susceptibility to vascular calcifications and fractures caused by a reduction in the levels of vitamin K dependent carboxylated enzymes, matrix Gla-protein (MGP) and bone Gla-protein or osteocalcin (BGP). In fact, while on one side warfarin is used to prevent embolism, on the other hand acting as a vitamin K antagonist it blocks the inhibitory effect of MGP on vascular calcification. Similarly, patients treated with warfarin carry a greater risk of developing osteoporosis and fractures, due to reduced BGP activity. Recently, a new generation of anticoagulant drugs has been developed, such as dabigatran, a direct thrombin inhibitor, and rivaroxaban, a direct factor-Xa inhibitor. They offer an interesting alternative to warfarin, because they do not require frequent blood tests for monitoring while offering similar results in terms of efficacy. Lacking the inhibitory effect on the vitamin K cycle, the consequent side effects can be avoided. If, compared to warfarin treated patients, a lower incidence of vascular calcifications and fractures will be demonstrated, the advantages over warfarin may be even greater, leading to further benefits in terms of morbidity and mortality.

Treatment with calcimimetic (cinacalcet) alters epoetin dosage requirements in dialysis patients: preliminary report.

BACKGROUND: Secondary hyperparathyroidism (SHPT), known complication of chronic renal failure, in addition to effects on bone and cardiovascular systems, is associated with reduced response to erythropoietin (EPO). Calcimimetics such as cinacalcet are the latest generation of drugs used in the treatment of SHPT. Few studies have evaluated the effect of cinacalcet on anemia associated with SHPT in dialysis patients, while no study has compared this cinacalcet effect with that of vitamin D analogs such as paricalcitol. PATIENTS AND METHODS: Using a retrospective chart-based review of dialysis patients' records to identify patients being treated with either cinacalcet or paricalcitol alone, matched for the same EPO treatment, which had been followed for 1 year, we have evaluated the effect of cinacalcet on anemia compared to that of paricalcitol. RESULTS: Ten patient records were found that fit the criteria, five treated with cinacalcet (Group 1) and five treated with paricalcitol (Group 2), all treated with the same dose of darbepoetin. Darbepoetin dosage was the only parameter that significantly changed between groups, decreasing in Group 1 (-33%, p = 0.009) while remaining unchanged in Group 2. PTH-level reduction, which was significant versus baseline in both groups, although not statistically different between groups, was higher with cinacalcet. CONCLUSION: The combination of lower EPO dose in cinacalcet-treated patients compared with paricalcitol-treated patients, along with good SHPT control is a novel information and might have considerable benefits in dialysis patients not only preventing bone (fractures) and cardiovascular system (calcifications) damages but also in terms of cost savings via a reduction of EPO dosage.