Chronic disease prevalence from Italian administrative databases in the VALORE project: a validation through comparison of population estimates with general practice databases and national survey.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

How different combinations of comorbidities affect healthcare use by elderly patients with obstructive lung disease.

Previous research had shown the number of comorbidities is a major factor influencing the burden of care for elderly patients with obstructive lung disease (OLD). This retrospective cohort study on a large population of elderly patients (age > 65 years) with OLD in northern Italy measures the use of healthcare resources associated with the most frequent combinations of comorbidities and investigates the most common reasons for hospitalization. Total health costs, pharmacy costs, emergency department (ED) visits, outpatient visits, and hospital admissions are assessed for every subject. The most common causes of hospitalization by a number of comorbidities and the most common sets of three comorbidities are identified. For each comorbidity group, we rank a list of the most frequent causes of hospitalization, both overall and avoidable with effective ambulatory care. A small group of patients suffering from major comorbidities accounts for the use of most healthcare resources. The most frequent causes of hospitalization are respiratory failure, heart failure, chronic bronchitis, and bronchopneumonia. The most common conditions manageable with ambulatory care among causes of hospitalizations are heart failure, bacterial pneumonia, and COPD. The set of three comorbidities responsible for the highest average total costs, and the highest average number of hospitalizations and outpatient visits comprised hypertension, cardiac arrhythmias, and heart failure. The main reasons for hospitalization proved to remain linked to heart failure and acute respiratory disease, regardless of specific combinations of comorbidities. Based on these findings, specific public health interventions among patients with OLD cannot be advised on the basis of specific sets of comorbidities only.

Healthcare Service Usage and Costs for Elderly Patients with Obstructive Lung Disease.

Background: The worldwide prevalence of obstructive lung disease (OLD) is increasing, especially among people >65 years old, and nearly three in four adults with OLD have two or more comorbid conditions. This study describes the impact of such comorbidities on the healthcare service usage and related costs in a country with universal health coverage, basing on a large cohort of elderly patients with OLD and employing real-world data. Methods: We carried out a retrospective cohort study on a large population of elderly (age >64 years) patients with OLD served by a Local Health Unit in northern Italy. Their comorbidities were assessed using the clinical diagnoses assigned by the Adjusted Clinical Group (ACG) system to individual patients by combining different information flows. Correlations between number of comorbidities and total annual healthcare service usage and costs were examined with Spearman's test. Regression models were applied to analyze the associations between the above-mentioned variables, adjusting for age and sex. Results: All types of healthcare service usage (access to emergency care; number of outpatient visits; number of hospital admissions) and pharmacy costs increased significantly with the number of comorbidities. Average total annual costs increased steadily with the number of comorbidities, ranging from € 1158.84 with no comorbidities up to € 9666.60 with 6 comorbidities or more. Poisson regression analyses showed an independent association between the number of comorbidities and the use of every type of healthcare service. Conclusion: These results based on real-world data provide evidence that the burden of care for OLD patients related to their comorbidities is independent of and in addition to the burden related to OLD alone and is strongly dependent on the number of comorbidities, suggesting a holistic approach to multimorbid patients with OLD is the most sound public health strategy.

[The validation of a nursing caseload score of home care patients]. / Validazione di un punteggio di gravosità assistenziale infermieristica per i pazienti delle cure domiciliari.

UNLABELLED: Identifying a measure of community nurses' workload is complicated due to the difficulty of capturing and standardizing the nature of community nursing across health care settings. AIM: Aim of this paper is to validate a workload/caseload nursing score for home care patients. METHODS: Patients of health care districts of Veneto region with at least two home care visits per month and a multi-dimensional and professional assessment were assesses with instruments used in routine care, adapted to the scope (a multidimensional assessment scale for frail elderly, that includes assessment of cognitive function, social support, mobility, functional status, health care needs); a list of patients needs. Time required for home care visits (excluded travelling time) was voluntarily registered in 5/8 districts. Uni and multivariate analyses were performed and a robust logistic regression accounting for skewed values. A tree regression analysis with CART Package model to identify conceptual nodes of the proposed classification was used. RESULTS: A group of 1298 of home care patients of 9 Districts were assessed and in 639 patients the time needed for home care visits was registered. The predictive value of the model on home care visits over 3 months was 44% while 59% for the time needed for nursing home care visits (number and length of nurses visits). CONCLUSION: A caseload score allows allocating nursing resources. The role of the family and of the overall environment should be accounted for. Patients need to be regularly re-assessed to capture any changes in their overall situation and needs.

A case-mix classification system for explaining healthcare costs using administrative data in Italy.

BACKGROUND: The Italian National Health Service (NHS) provides universal coverage to all citizens, granting primary and hospital care with a copayment system for outpatient and drug services. Financing of Local Health Trusts (LHTs) is based on a capitation system adjusted only for age, gender and area of residence. We applied a risk-adjustment system (Johns Hopkins Adjusted Clinical Groups System, ACG® System) in order to explain health care costs using routinely collected administrative data in the Veneto Region (North-eastern Italy). METHODS: All residents in the Veneto Region were included in the study. The ACG system was applied to classify the regional population based on the following information sources for the year 2015: Hospital Discharges, Emergency Room visits, Chronic disease registry for copayment exemptions, ambulatory visits, medications, the Home care database, and drug prescriptions. Simple linear regressions were used to contrast an age-gender model to models incorporating more comprehensive risk measures aimed at predicting health care costs. RESULTS: A simple age-gender model explained only 8% of the variance of 2015 total costs. Adding diagnoses-related variables provided a 23% increase, while pharmacy based variables provided an additional 17% increase in explained variance. The adjusted R-squared of the comprehensive model was 6 times that of the simple age-gender model. CONCLUSIONS: ACG System provides substantial improvement in predicting health care costs when compared to simple age-gender adjustments. Aging itself is not the main determinant of the increase of health care costs, which is better explained by the accumulation of chronic conditions and the resulting multimorbidity.

Association of Antidementia Drugs and Mortality in Community-Dwelling Frail Older Patients With Dementia: The Role of Mortality Risk Assessment.

OBJECTIVE: To evaluate whether treatment with antidementia drugs is associated with reduced mortality in older patients with different mortality risk at baseline. DESIGN: Retrospective. SETTING: Community-dwelling. PARTICIPANTS: A total of 6818 older people who underwent a Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA) evaluation to determine accessibility to homecare services or nursing home admission from 2005 to 2013 in the Padova Health District, Italy were included. MEASUREMENTS: Mortality risk at baseline was calculated by the Multidimensional Prognostic Index (MPI), based on information collected with the SVaMA. Participants were categorized to have mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) mortality risk. Propensity score-adjusted hazard ratios (HR) of 2-year mortality were calculated according to antidementia drug treatment. RESULTS: Patients treated with antidementia drugs had a significant lower risk of death than untreated patients (HR 0.82; 95% confidence interval [CI] 0.73-0.92 and 0.56; 95% CI 0.49-0.65 for patients treated less than 2 years and more than 2 years treatment, respectively). After dividing patients according to their MPI-SVaMA grade, antidementia treatment was significantly associated with reduced mortality in the MPI-SVaMA-1 mild (HR 0.71; 95% CI 0.54-0.92) and MPI-SVaMA-2 moderate risk (HR 0.61; 95% CI 0.40-0.91, matched sample), but not in the MPI-SVaMA-3 high risk of death. CONCLUSIONS: This large community-dwelling patient study suggests that antidementia drugs might contribute to increased survival in older adults with dementia with lower mortality risk.

Components of the metabolic syndrome and incidence of diabetes in elderly Italians: the Italian Longitudinal Study on Aging.

The aim of this study was to explore the relationship among components of the metabolic syndrome and their role in the development of diabetes. We included 2295 subjects, aged 65-84 years, participating in the Italian Longitudinal Study on Aging, a population-based study conducted in 1992 and with a follow-up in 1996. Factor analysis was conducted, separately for diabetic and non-diabetic men and women, using the principle components method and varimax rotations. Factor scores for the baseline were used as independent variables in logistic regressions models to determine risk factors predicting the development of diabetes. Factor analysis among non-diabetic elderly showed two factors for men (body size/insulin resistance, blood pressure/lipids) and three for women (body size, lipids, blood pressure). Among diabetic subjects, three factors emerged for men (body size/lipids/insulin resistance, body size/blood pressure, glucose) and four for women (body size/lipids/insulin resistance, lipids, body size/glucose/insulin resistance, lipids/blood pressure). For non-diabetic men and women, the body size factor (body size/insulin resistance factor for men) was strongly associated with diabetes incidence (OR=2.30, 95% CI 1.41-3.74 and OR=2.06, 95% CI 1.33-3.17, respectively). This study confirms that the metabolic syndrome (MetS) does not recognize one single underlying factor in an elderly cohort and that the obesity factor is a strong predictor of development of new onset diabetes.

Metabolic syndrome, diabetes, and cardiovascular disease in an elderly Caucasian cohort: the Italian Longitudinal Study on Aging.

BACKGROUND: The metabolic syndrome (MetS) is represented by a cluster of risk factors for cardiovascular diseases (CVDs). In spite of its high frequency and strong association with morbidity and mortality in the adult population, little is known about its magnitude in elderly persons. METHODS: We assessed the prevalence of MetS by diabetic status and sex in the participants in the Italian Longitudinal Study on Aging (ILSA), a population-based study on a sample of 5632 individuals 65-84 years old at baseline (1992). We measured the association of MetS with stroke, coronary heart disease, and diabetes at baseline and with CVD mortality at 4-year follow-up. RESULTS: The prevalence of MetS was 25.9% in nondiabetic men and 55.2% in nondiabetic women; in diabetic individuals it was 64.9% and 87.1% in men and women, respectively. At baseline, in both men and women there was a significant association with stroke (odds ratio [OR]=1.67, 95% confidence interval [CI], 1.02-2.75 in men and OR=1.72, CI, 1.01-2.93 in women) and diabetes (OR=4.58, CI, 3.12-6.74 in men and OR=5.15, CI, 3.23-8.20 in women). A significant association with chronic heart disease was found in men only (OR=1.40; CI, 1.02-1.97). During the approximately 4-year follow-up, nondiabetic men with MetS had a risk of CVD mortality 12% higher compared to those without MetS, whereas no significant differences were found in women. CONCLUSIONS: MetS is very common in aged Italians, and it is associated with stroke and diabetes in both sexes, and with chronic heart disease in men. In men, it increases significantly the risk of CVD mortality.

Recurrent aphthous stomatitis as an expression of pathergy in atopics.

BACKGROUND: Recurrent Aphthous Stomatitis (RAS) may be part of the "atopic background". Recently it has been reported that aphtous stomatitis could be an expression of atopic diathesis. The aim of this study is to verify whether the prevalence of posttraumatic aphthae is higher in patients with RAS and atopic diathesis than in patients with RAS without atopy. MATERIAL AND METHODS: In the past three years 39 new patients between 14 and 56 years of age and affected by idiopathic RAS have been observed. Atopic status and history of posttraumatic aphthosis were evaluated in all patients. RESULTS: The results appear to show that in our population the prevalence of posttraumatic aphthae is higher among atopic patients. CONCLUSIONS: Not only RAS but also pathergy could be considered an expression of the rich clinical/ symptomatic constellation of atopic diathesis.

Warfarin Treatment and All-Cause Mortality in Community-Dwelling Older Adults with Atrial Fibrillation: A Retrospective Observational Study.

OBJECTIVES: To investigate the relationship between warfarin treatment and different strata of all-cause mortality risk assessed using the Multidimensional Prognostic Index (MPI) based on information collected using the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA) in community-dwelling older adults with atrial fibrillation (AF). DESIGN: Retrospective observational study. SETTING: Older community-dwelling adults who underwent a SVaMA evaluation establishing accessibility to homecare services and nursing home admission from 2005 to 2013 in the Padova Health District, Italy. PARTICIPANTS: Community-dwelling individuals with AF aged 65 and older (N = 1,827). MEASUREMENTS: Participants were classified as being at mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), or severe (MPI-SVaMA-3) risk of mortality using the MPI-SVaMA, a validated prognostic tool based on age, sex, comorbidity, cognitive status, mobility and functional disability, pressure sore risk, and social support. The association between warfarin treatment and mortality was tested using multivariate- and propensity score-adjusted Cox regression models, controlling for age, sex, all SVaMA domains, concomitant diseases, and drug treatments. RESULTS: Higher MPI-SVaMA scores were associated with lower rates of warfarin treatment and higher 3-year mortality. After adjustment for propensity score quintiles, warfarin treatment was significantly associated with lower 2-year mortality in individuals with MPI-SVaMA-1 (hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.50-0.82), MPI-SVaMA-2 (HR = 0.68, 95% CI = 0.55-0.85), and MPI-SVaMA-3 (HR = 0.55, 95% CI = 0.44-0.67). Heterogeneity analyses confirmed that the effect of warfarin treatment was not different between MPI-SVaMA groups (P for heterogeneity = .48). CONCLUSION: Community-dwelling older adults with AF benefitted from anticoagulation in terms of lower all-cause mortality over a mean follow-up of 2 years, regardless of poor health and functional condition. Although this benefit can be ascribed to the treatment, it may also reflect better overall care.

Relation of Statin Use and Mortality in Community-Dwelling Frail Older Patients With Coronary Artery Disease.

Clinical decision-making for statin treatment in older patients with coronary artery disease (CAD) is under debate, particularly in community-dwelling frail patients at high risk of death. In this retrospective observational study on 2,597 community-dwelling patients aged ≥65 years with a previous hospitalization for CAD, we estimated mortality risk assessed with the Multidimensional Prognostic Index (MPI), based on the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA), used to determine accessibility to homecare services/nursing home admission in 2005 to 2013 in the Padua Health District, Veneto, Italy. Participants were categorized as having mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) baseline mortality risk, and propensity score-adjusted hazard ratios (HRs) of 3-year mortality rate were calculated according to statin treatment in these subgroups. Greater MPI-SVaMA scores were associated with lower rates of statin treatment and higher 3-year mortality rate (MPI-SVaMA-1 = 23.4%; MPI-SVaMA-2 = 39.1%; MPI-SVaMA-3 = 76.2%). After adjusting for propensity score quintiles, statin treatment was associated with lower 3-year mortality risk irrespective of MPI-SVaMA group (HRs [95% confidence intervals] 0.45 [0.37 to 0.55], 0.44 [0.36 to 0.53], and 0.28 [0.21 to 0.39] in MPI-SVaMA-1, -2, and -3 groups, respectively [interaction test p = 0.202]). Subgroup analyses showed that statin treatment was also beneficial irrespective of age (HRs [95% confidence intervals] 0.38 [0.27 to 0.53], 0.45 [0.38 to 0.54], and 0.44 [0.37 to 0.54] in 65 to 74, 75 to 84, and ≥85 year age groups, respectively [interaction test p = 0.597]). In conclusion, in community-dwelling frail older patients with CAD, statin treatment was significantly associated with reduced 3-year mortality rate irrespective of age and multidimensional impairment, although the frailest patients were less likely to be treated with statins.

Knowledge of sexually transmitted diseases and condom use among female street sex workers in Padua.

OBJECTIVES: The aim of the present study was to investigate knowledge of sexually transmitted diseases (STDs) and condom use in a population of young female street sex workers from eastern Europe and other non-EU countries based in the Padua area (north-eastern Italy). To assess whether any aspects of their behavior might foster the spread of STDs. STUDY DESIGN: Street sex workers (prostitutes) were approached on the streets or during non-STD medical appointments, their knowledge of STDs and condom use were evaluated. They were asked to answer an anonymous questionnaire comprising 16 questions. RESULTS: 98 of them cooperated. Over one third of the sample frequently did not use a condom. This finding was inversely correlated with their age and educational level. Almost all the street sex workers were aware of AIDS but far less of other STDs. Most were almost totally unacquainted with some of them. We found a statistically significant correlation between condom use and their age, and between condom use and educational level. CONCLUSIONS: Sex workers often engaged in unprotected intercourse with clients, they practiced their profession even in the presence of STD-related symptoms and did not use a condom during intercourse with non-paying partners or pimps. The irresponsible behavior of some Italian paying partners prepared to pay extra for unprotected sex, increases the risk of acquiring STDs. The intercourse with female street sex workers can be considered a risk behavior for contracting STDs.

Statin Treatment and Mortality in Community-Dwelling Frail Older Patients with Diabetes Mellitus: A Retrospective Observational Study.

BACKGROUND: Older adults are often excluded from clinical trials. Decision making for administration of statins to older patients with diabetes mellitus (DM) is under debate, particularly in frail older patients with comorbidity and high mortality risk. We tested the hypothesis that statin treatment in older patients with DM was differentially effective across strata of mortality risk assessed by the Multidimensional Prognostic Index (MPI), based on information collected with the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA). METHODS: In this retrospective observational study, we estimated the mortality risk in 1712 community-dwelling subjects with DM ≥ 65 years who underwent a SVaMA evaluation to establish accessibility to homecare services/nursing home admission from 2005 to 2013 in the Padova Health District, Italy. Mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) risk of mortality at baseline and propensity score-adjusted hazard ratios (HR) of three-year mortality were calculated according to statin treatment. RESULTS: Higher MPI-SVaMA scores were associated with lower rates of statin treatment (MPI-SVaMA-1 = 39% vs MPI-SVaMA-2 = 36% vs MPI-SVaMA-3 = 24.9%. p<0.001) and higher three-year mortality (MPI-SVaMA-1 = 12.9% vs MPI-SVaMA-2 = 24% vs MPI-SVaMA-3 = 34.4%, p<0.001). After adjustment for propensity score quintiles, statin treatment was significantly associated with lower three-year mortality irrespective of MPI-SVaMA group (interaction test p = 0.303). HRs [95% confidence interval (CI)] were 0.19 (0.14-0.27), 0.28 (0.21-0.36), and 0.26 (0.20-0.34) in the MPI-SVaMA-1, MPI-SVaMA-2, and MPI-SVaMA-3 groups, respectively. Subgroup analyses showed that statin treatment was also beneficial irrespective of age. HRs (95% CI) were 0.21 (0.15-0.31), 0.26 (0.20-0.33), and 0.26 (0.20-0.35) among patients aged 65-74, 75-84, and ≥ 85 years, respectively (interaction test p=0.812). CONCLUSIONS: Statin treatment was significantly associated with reduced three-year mortality independently of age and multidimensional impairment in community-dwelling frail older patients with DM.

Can Italian healthcare administrative databases be used to compare regions with respect to compliance with standards of care for chronic diseases?

BACKGROUND: Italy has a population of 60 million and a universal coverage single-payer healthcare system, which mandates collection of healthcare administrative data in a uniform fashion throughout the country. On the other hand, organization of the health system takes place at the regional level, and local initiatives generate natural experiments. This is happening in particular in primary care, due to the need to face the growing burden of chronic diseases. Health services research can compare and evaluate local initiatives on the basis of the common healthcare administrative data.However reliability of such data in this context needs to be assessed, especially when comparing different regions of the country. In this paper we investigated the validity of healthcare administrative databases to compute indicators of compliance with standards of care for diabetes, ischaemic heart disease (IHD) and heart failure (HF). METHODS: We compared indicators estimated from healthcare administrative data collected by Local Health Authorities in five Italian regions with corresponding estimates from clinical data collected by General Practitioners (GPs). Four indicators of diagnostic follow-up (two for diabetes, one for IHD and one for HF) and four indicators of appropriate therapy (two each for IHD and HF) were considered. RESULTS: Agreement between the two data sources was very good, except for indicators of laboratory diagnostic follow-up in one region and for the indicator of bioimaging diagnostic follow-up in all regions, where measurement with administrative data underestimated quality. CONCLUSION: According to evidence presented in this study, estimating compliance with standards of care for diabetes, ischaemic heart disease and heart failure from healthcare databases is likely to produce reliable results, even though completeness of data on diagnostic procedures should be assessed first. Performing studies comparing regions using such indicators as outcomes is a promising development with potential to improve quality governance in the Italian healthcare system.

Development and validation of a Multidimensional Prognostic Index for mortality based on a standardized Multidimensional Assessment Schedule (MPI-SVaMA) in community-dwelling older subjects.

OBJECTIVES: To develop and validate a Multidimensional Prognostic Index (MPI) for mortality based on information collected by the Multidimensional Assessment Schedule (SVaMA), the recommended standard tool for multidimensional assessment of community-dwelling older subjects in seven Italian regions. DESIGN: Prospective cohort study. PARTICIPANTS: Community-dwelling subjects older than 65 years who underwent an SVaMA evaluation from 2004 to 2010 in Padova Health District, Veneto, Italy. MEASUREMENTS: The MPI-SVaMA was calculated as a weighted (weights were derived from multivariate Cox regressions) linear combination of the following nine domains: age, sex, main diagnosis, and six scores, ie, the Short Portable Mental Status Questionnaire, the Barthel index (contains two domains: activities of daily living and mobility), the Exton-Smith scale, the Nursing Care Needs, and the Social Network Support by a structured interview. Subjects were followed for a median of 2 years; those who had not died were followed for at least 1 year. The MPI-SVaMA score ranged from 0 to 1 and 3 grades of severity of the MPI-SVaMA were calculated on the basis of estimated cutoffs. Discriminatory power and calibration were further assessed. RESULTS: A total of 12,020 subjects (mean age 81.84 ± 7.97 years) were included. Two random cohorts were selected: (1) a development cohort, ie, 7876 subjects (mean age 81.79 ± 8.05, %females: 63.1) and (2) a validation cohort, ie, 4144 subjects (mean age: 81.95 ± 7.83, %females: 63.7). The discriminatory power for mortality of MPI-SVaMA was 0.828 (95% CI 0.817-0.838) and 0.832 (95% CI 0.818-0.845) at 1 month and 0.791 (95% CI 0.784-0.798) and 0.792 (95% CI 0.783-0.802) at 1 year in development and validation cohorts, respectively. MPI-SVaMA results were well calibrated showing lower than 10% differences between predicted and observed mortality, both in development and validation cohorts. CONCLUSIONS: The MPI-SVaMA is an accurate and well-calibrated prognostic tool for mortality in community-dwelling older subjects, and can be used in clinical decision making.

Iron deficiency differently affects metabolic responses in soybean roots.

Iron deficiency responses were investigated in roots of soybean, a Strategy I plant species. Soybean responds to iron deficiency by decreasing growth, both at the root and shoot level. Chlorotic symptoms in younger leaves were evident after a few days of iron deficiency, with chlorophyll content being dramatically decreased. Moreover, several important differences were found as compared with other species belonging to the same Strategy I. The main differences are (i) a lower capacity to acidify the hydroponic culture medium, that was also reflected by a lower H(+)-ATPase activity as determined in a plasma membrane-enriched fraction isolated from the roots; (ii) a drastically reduced activity of the phosphoenolpyruvate carboxylase enzyme; (iii) a decrease in both cytosolic and vacuolar pHs; (iv) an increase in the vacuolar phosphate concentration, and (v) an increased exudation of organic carbon, particularly citrate, phenolics, and amino acids. Apparently, in soybean roots, some of the responses to iron deficiency, such as the acidification of the rhizosphere and other related processes, do not occur or occur only at a lower degree. These results suggest that the biochemical mechanisms induced by this nutritional disorder are differently regulated in this plant. A possible role of inorganic phosphate in the balance of intracellular pHs is also discussed.

Renal protection in diabetes: role of glycemic control.

Diabetes is the most common cause of ESRD in Western countries. This article describes the impact of glycemic control in the various stages of the disease and considers the impact of tight glycemic control on the development and progression of diabetic nephropathy (DN). The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetic Study have demonstrated in type 1 and type 2 diabetes that intensive glycemic control significantly reduces the risk for development of microalbuminuria. Although observational studies suggest an impact of glycemia also on the progression of DN, fewer data are available on the impact of improved metabolic control in secondary prevention. The long-term follow-up of the patients who participated in the Diabetes Control and Complications Trial (Epidemiology of Diabetes Interventions and Complications Study) demonstrated a sustained effect of previous tight glycemic control on both development and progression of DN. Finally, long-term normoglycemia, achieved by pancreas transplantation, is able not only to prevent the development of early diabetic glomerulopathy in kidney transplant recipients but also to halt progression and induce regression of the established diabetic renal lesions in nonuremic patients. Taken together, these studies strongly demonstrate that improvement in glucose control is the most important therapeutic approach in primary prevention. Tight glycemic control also is important in slowing progression of DN, and if blood glucose is normalized, then regression of DN can be achieved. Therefore, a target of glycated hemoglobin levels <7% should be recommended in all patients with diabetes.

Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes.

Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by 51Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P < 0.03 and P < 0.001, respectively). GBM width and Vv(mes/glom) increased from normoalbuminuric to proteinuric patients [P < 0.005 normoalbuminuric and microalbuminuric versus proteinuric for GBM, P < 0.01 normoalbuminuric versus proteinuric for Vv(mes/glom)]. In patients with increased GBM width (> 396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r = 0.33, P < 0.002) and IL-6 (r = 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy.