The data project: a shared approach between stakeholders of the healthcare system in definition of a therapeutic algorithm for inflammatory arthritis.

Rheumatic musculoskeletal diseases or RMD [rheumatoid arthritis (RA) and spondyloarthritis (SpA)] are systemic inflammatory diseases for which there are no biomarkers capable of predicting treatments with a higher likelihood of response in naive patients. In addition, the expiration of the anti-TNF blocking drugs' patents has resulted in the availability of anti-TNF biosimilar drugs with the same efficacy and safety than originators but at significantly reduced prices. To guarantee a personalized therapeutic approach to RMD treatment, a board of rheumatologists and stakeholders from the Campania region, Italy, developed a clinically applicable arthritis therapeutic algorithm to guide rheumatologists (DATA project). The general methodology relied on a Delphi technique forecast to produce a set of statements that summarized the experts' consensus. Selected clinical scenarios were discussed in light of the available evidence, and there were two rounds of voting on the therapeutic approaches. Separate discussions were held regarding rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The decision-making factors for each disease were clinical presentation, demographics, and comorbidities. In this paper, we describe a virtuous process between rheumatologists and healthcare system stakeholders that resulted in the development of a shared therapeutic algorithm for RMD patients naive to bDMARDs.

Ethnobotany of dye plants in Southern Italy, Mediterranean Basin: floristic catalog and two centuries of analysis of traditional botanical knowledge heritage.

BACKGROUND: Since ancient times, man has learned to use plants to obtain natural dyes, but this traditional botanical knowledge (TBK) is eroding. In the late, during, and the early 1800s, there was an increase in research related to dye species, and this allowed the development of industry and economy in rural contexts of Southern Italy. Today, dyes are mainly obtained from synthetic products, and this leads to risks for human health related to pollution. METHODS: Starting from the literature, three catalogs of the dyeing species (plants, algae, fungi, and lichens) used in the Mediterranean Basin and mainly in Southern Italy have been created. Percentages of parts used and colors extracted from species have been recorded and analyzed. The plant species present in the catalogs have been verified in the territories of Southern Italy, and the data have been registered. An ethnobotanical survey was conducted, in the region of Southern Italy, to verify the erosion level of traditional botanical knowledge, linked to the ethnobotanical dyeing, over time. RESULTS: A total of 524 species were recorded among plants, algae, fungi, and lichens, and related parts used and extracted pigments. Most uses concern the stems and leaves, and the most frequent color is yellow. From the on-field survey operations, 283 plant species have been verified. These represent 64.31% of the species reported in the flora of the dye plants produced. The results, from the ethnobotanical survey, show that only 8.6% of TBK remained in the collective memory. CONCLUSIONS: This catalog is among the largest in this sector and is the basis for studies related to the restoration of an eco-sustainable economy which would allow the development of marginal areas present throughout Southern Italy.

Health tourism: an opportunity for sustainable development.

In February 2017, the "Programma Mattone Internazionale Salute" (ProMis), that is the Italian Program for Internationalization of Regional Health Systems of the Ministry of Health (MoH), presented the first version of its Position Paper on Health Tourism, which embeds a first shared approach to the recommendations expressed by the European Committee of Regions (CoR) on "Age-Friendly" tourism. The CoR stresses the importance of local and regional authorities in the coordination of multi-sectoral policies such as healthcare, social assistance, transport, urban planning and rural development in relation to the promotion of mobility, security, accessibility of services, including health care and social services. "Age-friendly" tourism is an example of an innovative tourist offer that strives to meet the health needs of the entire "traveling" population, with an integrated and cross-sector approach that involves various organizations operating in sectors such as healthcare, accessibility and transport. The aim of the workshop was to explore the interest of the stakeholders to participate in a systemic action in the field of "health" tourism, and to identify priority implementation areas that offer opportunities to take advantage of validated, innovative experiences that strengthen the accessibility to health and social services in regional, national and international contexts. This effort provides the opportunity to take advantage of aligning the European Structural and Investment Funds (ESIF) to the development of tourism, coherently with the needs and resources of local and regional health authorities.

Innovative Approaches to Active and Healthy Ageing: Campania Experience to Improve the Adoption of Innovative Good Practices.

The demographic projections on the European population predict that people aged over 60 will increase by about two million/year in the next decades. Since 2012, the Campania Reference Site of the European Innovation Partnership on Active and Healthy Ageing supports the innovation of the Regional Health System, to face up demographic changes and sustainability. Campania Reference Site provides the opportunity to connect loco-regional stakeholders in social and health care services (universities, healthcare providers, social services, local communities and municipalities), with international organizations, in order to adopt and scale up innovative solutions and approaches. This paper describes the building process of Campania Reference Site and the main results achieved, that have been allowing it to become a hub for open innovation in the field of active and healthy aging at regional, national and international level.

Implementing an ICT-Based Polypharmacy Management Program in Italy.

Although there is evidence of a growing awareness of the problem, no official policy statements or regulatory guidelines on polypharmacy have been released up to date by Italian Health Authorities. Medication review, application of appropriateness criteria and computerized prescription support systems are all possible approaches in order to improve the quality of prescribing in older persons. More focused training courses on multimorbidity and polytherapy management are encouraged. Furthermore a multidisciplinary approach integrating different health care professionals (physicians, pharmacists, and nurses) may positively impact on reducing the sense of fear related to discontinue or substitute drugs prescribed by others; the fragmentation of therapy among different specialists; reducing costs; and improving adverse drug reaction detection and reporting. Aiming at achieving the individualized pharmacotherapy, a multidisciplinary approach starting with identification of patients and risk for drug-related problems, followed by medication review overtime and use of inappropriateness criteria, supported by computerized systems has been proposed.

Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation.

OBJECTIVE: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of studying clinical variability as observed for presenilin 1 (PSEN1) mutations. Two early-onset FAD (EOFAD) Calabrian families with PSEN1 Met146Leu (ATG/CTG) mutation constitute a unique population descending from a remote common ancestor. Recently, several other EOFAD families with the same mutation have been described worldwide. METHODS: We searched for a common founder of the PSEN1 Met146Leu mutation in families with different geographic origins by genealogic and molecular analyses. We also investigated the phenotypic variability at onset in a group of 50 patients (mean age at onset 40.0 +/- 4.8 years) by clinical, neuropsychological, and molecular methodologies. RESULTS: EOFAD Met146Leu families from around the world resulted to be related and constitute a single kindred originating from Southern Italy before the 17th century. Phenotypic variability at onset is broad: 4 different clinical presentations may be recognized, 2 classic for AD (memory deficits and spatial and temporal disorientation), whereas the others are expressions of frontal impairment. The apathetic and dysexecutive subgroups could be related to orbital-medial prefrontal cortex and dorsolateral prefrontal cortex dysfunction. CONCLUSIONS: Genealogic and molecular findings provided evidence that the PSEN1 Met146Leu families from around the world analyzed in this study are related and represent a single kindred originating from Southern Italy. The marked phenotypic variability might reflect early involvement by the pathologic process of different cortical areas. Although the clinical phenotype is quite variable, the neuropathologic and biochemical characteristics of the lesions account for neurodegenerative processes unmistakably of Alzheimer nature.

Frontal Behavioural Inventory in the differential diagnosis of dementia.

OBJECTIVE: To evaluate diagnostic properties of the Frontal Behavioural Inventory (FBI) in patients suffering from different forms of dementia. METHODS: The FBI was administered with other psychometric tests investigating cognitive performances and behavioral scales to the caregivers of 35 patients with the frontal variant of frontotemporal dementia (fv-FTD), 22 patients with Alzheimer's disease (AD) and 15 with vascular dementia (VaD). All patients were comparable for degree of dementia severity and level of executive impairment. RESULTS: The FBI showed high concurrent validity, internal consistency and good inter-rater and test-retest reliability. The discriminant validity was also very high. A new FBI cut-off score of 23 gave 97% sensitivity and 95% specificity in distinguishing fv-FTD from non-FTD patients. Conversely, the Neuropsychiatic Inventory (NPI) score was unable to differentiate fv-FTD from AD. CONCLUSIONS: The FBI is a neurobehavioral tool suitable to distinguish fv-FTD from other forms of dementia also when data from cognitive testing or other behavioral scales fail to support the differential diagnosis.

Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels are considered a risk factor for cerebrovascular disease and may also play an important role in the pathogenesis of Alzheimer's disease (AD). High values of plasma tHcy and low levels of vitamin B(12) and folate are frequently present in AD patients. Moreover, the homozygous mutation (C677T) of the methylene tetrahydrofolate reductase (MTHFR) gene, related to a thermolabile type of the encoded enzyme, causes hyperhomocysteinemia by reducing the 5-methyltetrahydrofolate availability. OBJECTIVE: The aim of the study was to investigate plasma levels of folate, vitamin B(12) and tHcy in patients with AD. These values were also related to the severity and the duration of the disease and to the possible role of the MTHFR genotype (C677T). METHOD: Plasma tHcy levels, homozygosity for the C677T mutation of the MTHFR gene, and folate and vitamin B(12) plasma levels were evaluated in 74 patients with AD (45 men, 29 women, mean age 68 years) and in 74 healthy matched controls (42 men, 32 women, mean age 68 years). RESULTS: AD patients had higher mean (+/- SD) plasma levels of tHcy (20.9 +/- 15 micromol/l compared to 11.8 +/- 5 micromol/l, p < 0.001) and lower mean plasma folate (5.7 +/- 2.1 ng/ml compared to 8.5 +/- 3.2 ng/ml, p < 0.001) and vitamin B(12) (491 +/- 144 pmol/l compared to 780 +/- 211 pmol/l, p < 0.001) concentrations. Homozygosity for the C677T mutation of the MTHFR gene had a similar prevalence among controls (18%) and AD patients (20%). Homozygous AD patients (n = 15) had higher plasma tHcy values than nonhomozygotes, in spite of similar mean plasma folate and vitamin B(12) levels. This difference in plasma tHcy levels was not observed in controls. Patients with levels of plasma tHcy above and of plasma folate below the normal limits were more frequent in the homozygous AD group. The duration of the disease correlated with plasma levels of tHcy (r = +0.832, p < 0.001), plasma folate (r = -0.580, p < 0.05), and vitamin B(12) (r = -0.460, p < 0.05). However, when all the data were corrected for age, serum creatinine levels, and duration of the disease, mean plasma tHcy, folate, and vitamin B(12) levels were not statistically different between controls and AD patients. CONCLUSIONS: Our data suggest that rather than a risk factor for AD, hyperhomocysteinemia is related to its progression and increasing severity. This might be particularly relevant in homozygotes for the C677T mutation of the MTHFR gene and supports the possible need for continuous supplements in this setting.

Blood-brain barrier transport and brain metabolism of glucose during acute hyperglycemia in humans.

It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMR(glc)) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and [(18)F]fluorodeoxyglucose as tracer. The Kety-Schmidt technique was used for measurement of cerebral blood flow (CBF). After 2 h of hyperglycemia (15.7 +/- 0.7 mmol/L), the glucose permeability-surface area product from blood to brain remained unchanged (0.050 +/- 0.008 vs. 0.059 +/- 0.031 mL/100 g.min). The unidirectional clearance of [(18)F]fluorodeoxyglucose (K(1)*) was reduced from 0.108 +/- 0.011 to 0.061 +/- 0.005 mL/100 g.min (P < 0.0004). During hyperglycemia, global CMR(glc) remained constant (21.4 +/- 1.2 vs. 23.1 +/- 2.2 micromol/100 g.min, normo- and hyperglycemia, respectively). Except for a significant increase in white matter CMR(glc), no regional difference in CMR(glc) was found. Likewise, CBF remained unchanged. The reduction in K(1)* was compatible with Michaelis-Menten kinetics for facilitated transport. Our findings indicate no major adaptational changes in the maximal transport velocity or affinity to the blood-brain barrier glucose transporter. Finally, hyperglycemia did not change global CBF or CMR(glc).

Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype.

Seventy-one mutations of the low density lipoprotein (LDL) receptor gene were identified in 282 unrelated Italian familial hypercholesterolemia (FH) heterozygotes. By extending genotype analysis to families of the index cases, we identified 12 mutation clusters and localized them in specific areas of Italy. To evaluate the impact of these mutations on the clinical expression of FH, the clusters were separated into 2 groups: receptor-defective and receptor-negative, according to the LDL receptor defect caused by each mutation. These 2 groups were comparable in terms of the patients' age, sex distribution, body mass index, arterial hypertension, and smoking status. In receptor-negative subjects, LDL cholesterol was higher (+18%) and high density lipoprotein cholesterol lower (-5%) than the values found in receptor-defective subjects. The prevalence of tendon xanthomas and coronary artery disease (CAD) was 2-fold higher in receptor-negative subjects. In patients >30 years of age in both groups, the presence of CAD was related to age, arterial hypertension, previous smoking, and LDL cholesterol level. Independent contributors to CAD in the receptor-defective subjects were male sex, arterial hypertension, and LDL cholesterol level; in the receptor-negative subjects, the first 2 variables were strong predictors of CAD, whereas the LDL cholesterol level had a lower impact than in receptor-defective subjects. Overall, in receptor-negative subjects, the risk of CAD was 2.6-fold that of receptor-defective subjects. Wide interindividual variability in LDL cholesterol levels was found in each cluster. Apolipoprotein E genotype analysis showed a lowering effect of the epsilon2 allele and a raising effect of the epsilon4 allele on the LDL cholesterol level in both groups; however, the apolipoprotein E genotype accounted for only 4% of the variation in LDL cholesterol. Haplotype analysis showed that all families of the major clusters shared the same intragenic haplotype cosegregating with the mutation, thus suggesting the presence of common ancestors.

Measurement of global brain atrophy in Alzheimer's disease with unsupervised segmentation of spin-echo MRI studies.

In 16 patients with probable Alzheimer's disease (AD; NINDS criteria, age range 56-78 years), gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) absolute and fractional volumes were measured with an unsupervised multiparametric post-processing segmentation method based on estimates of relaxation rates R1, R2 (R1 = 1/T1; R2 = 1/T2) and proton density [N(H)] from conventional spin-echo studies (Alfano et al. Magn. Reson. Med. 1997;37:84-93). Global brain atrophy, and GM and WM fractions significantly correlated with Mini-Mental Status Examination and Blessed Dementia Scale scores. Compared with normals, brain compartments in AD patients showed decreased GM (-6.84 +/- 1.58%) and WM fractions (-9.79 +/- 2.47%) and increased CSF fractions (+58.80 +/- 10.37%). Changes were more evident in early-onset AD patients. In AD, measurement of global brain atrophy obtained by a computerized procedure based on routine magnetic resonance studies could complement the information provided by neuropsychological tests for the assessment of disease severity.

Social class, coronary risk factors and undernutrition, a double burden of diseases, in women during transition, in five Indian cities.

OBJECTIVE: To find out the association between social class and coronary risk factors in women. DESIGN AND SETTING: Cross-sectional surveys were conducted in six-twelve urban streets in each of five cities from various regions of India following a common study protocol and criteria of diagnosis. SUBJECTS AND METHODS: We randomly selected 3257 women, aged 25-64 years inclusive, from the cities of Moradabad (n=902), Trivandrum (n=760) Calcutta (n=410), Nagpur (n=405) and Bombay (n=780). Evaluation was by questionnaires validated at Moradabad. All subjects, after pooling of data, were divided into social class 1 (n=985), social class 2 (n=790), social class 3 (n=674), social class 4 (n=602) and social class 5 (n=206), based on various attributes of socioeconomic status. RESULTS: The prevalence of hypertension, diabetes mellitus, family history of coronary disease, obesity, central obesity and sedentary lifestyle were significantly associated with higher social classes and tobacco consumption was not associated with social class. Oral contraceptive intake and postmenopausal status were also more common among higher social classes, which may be due to more education and a longer lifespan among the higher social classes, respectively. Mean total cholesterol, high density lipoprotein cholesterol, systolic and diastolic blood pressure, mean body mass index and waist-hip ratio showed significant association with higher social classes. Mean age, body weight, body mass index, waist-hip ratio, systolic and diastolic blood pressure, total cholesterol and 2-h blood glucose were significantly positively correlated with social class, as assessed by Spearman's rank correlation. Higher social classes 1-3 were more common in Trivandrum and Bombay than in Moradabad. The prevalence of hypertension, diabetes mellitus and being overweight (body mass index >25 kg/m2) were also more common in Trivandrum and Bombay compared to Moradabad. Undernutrition was negatively associated with higher social classes and was more common in Moradabad and Nagpur than Trivandrum. CONCLUSIONS: Higher social classes among Indian urban women have a higher prevalence of coronary risk factors, hypertension, diabetes mellitus, being overweight, central obesity, sedentary lifestyle, family history of coronary disease, oral contraceptive intake and postmenopausal status. Mean concentrations of total and high density lipoprotein cholesterol were also significantly associated with higher social classes.

Comparison between cortical distribution of I-123 iomazenil and Tc-99m HMPAO in patients with Alzheimer's disease using SPECT.

PURPOSE: To compare brain perfusion and synaptic density in Alzheimer's disease assessed using I-123 iomazenil SPECT with brain perfusion assessed using Tc-99m HMPAO SPECT. MATERIALS AND METHODS: Early and delayed I-123 iomazenil SPECT images acquired 20 and 180 minutes after injection were compared with Tc-99m HMPAO SPECT studies acquired 15 to 20 minutes after injection in five patients with Alzheimer's disease. RESULTS: Visual analysis of I-123 iomazenil images showed more severe (n = 4) and extensive (n = 3) defects than did Tc-99m HMPAO. Semiquantitative analysis was performed by normalizing the uptake of Tc-99m HMPAO and I-123 iomazenil in individual brain regions in the cerebellum and expressing these values as a ratio of the occipital regions. The analysis of brain regional ratios in Tc-99m HMPAO studies showed a low but significant correlation with ratios of delayed (r = 0.325, P < 0.05) images in the I-123 iomazenil studies. Furthermore, when compared with Tc-99m HMPAO, early (P < 0.01) and delayed mean ratios (P < 0.05) were significantly less in the frontal regions; early mean ratios were significantly less in the temporal regions (P < 0.05), and delayed (P < 0.05) mean ratios were significantly less in the parietal regions. CONCLUSIONS: Tc-99m HMPAO images were better correlated with I-123 iomazenil images, indicating cortical synaptic density (delayed images). I-123 iomazenil SPECT in patients with Alzheimer's disease provided more sensitive information than Tc-99m HMPAO, allowing evaluation of brain perfusion and synaptic density.

Association of central obesity and insulin resistance with high prevalence of diabetes and cardiovascular disease in an elderly population with low fat intake and lower than normal prevalence of obesity: the Indian paradox.

OBJECTIVE: To test the hypothesis that high prevalences of cardiovascular disease and diabetes in urban population of India are manifestations of insulin-resistance syndrome. DESIGN AND SETTING: Cross-sectional surveys were conducted in 20 streets in the city of Moradabad and in two villages. SUBJECTS AND METHODS: There were 566 subjects (255 rural and 311 urban) aged 60-84 years. All subjects were divided on the basis of their insensitivity to insulin into groups with mild, moderate and high insensitivity to insulin and data from both sexes were pooled for analysis. RESULTS: Overall increases in the prevalences of coronary disease, diabetes, hypertension, central obesity and associated disturbances were observed with increasing insensitivity to insulin and the trend was more significant among urban than it was among rural subjects. Multivariate logistic regression analysis revealed a significant positive association of level of insulin insensitivity with the age-adjusted prevalences of coronary disease, hypertension, diabetes, hypertriglyceridaemia, intolerance of glucose and central obesity among urban subjects. We observed a significant inverse association between insensitivity to insulin and physical activity both for rural and for urban subjects and between insensitivity to insulin and high-density lipoprotein cholesterol level for urban subjects. For rural subjects, we found significant associations of sensitivity to insulin with coronary artery disease and intolerance of glucose without significant associations with other risk factors. CONCLUSION: Insensitivity to insulin was significantly associated with risks of cardiovascular disease and diabetes, despite there being a low prevalence of obesity (9.0%) among urban subjects. Hypertension, diabetes, hypertriglyceridaemia, intolerance of glucose and central obesity were significantly associated with insensitivity to insulin and coronary disease for urban but not for rural people.

Peripheral body fat has a protective role on bone mineral density in elderly women.

OBJECTIVES: To determine whether bone mineral density is lower in women living in homes for the elderly as compared to free dwelling control subjects, and to investigate factors affecting possible differences. This is the first study with this objective as the primary aim. DESIGN: Case-control study. SUBJECTS AND METHODS: Institutionalised independent elderly women (n = 22, mean age = 75.1 y+/-6.43 s.d.) randomly selected in a home for the elderly and 22 age-matched control women randomly selected from a sample representative of the independent non institutionalised local population who underwent dual energy X-ray absorptiometry (DXA) at the lumbar spine and right femoral neck; anthropometric measurements (height, weight, subscapular and triceps skinfold thickness); general questionnaire. RESULTS: Mean bone mineral density at the femoral neck was 0.618 g/cm2 (+/-0.130s.d.) in institutionalised women and 0.709 g/cm2 (+/-0.106 s.d.) in controls (P = 0.02, t-test). Controlling for confounding factors in the analysis of covariance, triceps skinfold thickness and living in a home for the elderly turned out to be significant determinants of bone mineral density. CONCLUSION: When compared to free dwelling control subjects, institutionalised women show lower bone density, that is the main risk factor for fracture. Reduced peripheral body fat was significantly associated with the low bone mineral density observed. Health programs aimed at decreasing the incidence of fractures among institutionalised subjects will also have to consider the effect of nutritional or life style factors that reduce peripheral body fat.

Cerebral blood flow in spinocerebellar degenerations: a single photon emission tomography study in 28 patients.

We used single photon emission tomography to study regional cerebral perfusion in patients with different forms of spinocerebellar degeneration: 6 patients with Friedreich's ataxia (FA), 6 with early-onset cerebellar ataxia with retained tendon reflexes (EOCA), 5 with autosomal dominant cerebellar ataxia type 1 (ADCA I) and 11 with idiopathic late-onset cerebellar ataxia (ILOCA). The results were related to clinical and magnetic resonance imaging (MRI) findings. Cerebellar hypoperfusion was constant in ADCA I and frequent in patients with other spinocerebellar degenerations. Brain stem hypoperfusion was constant in ADCA I, frequent in ILOCA patients with pontocerebellar atrophy and absent in FA and EOCA. FA and EOCA often showed a reduction in the parietotemporal cortex blood flow, which was not related to cortical atrophy. ILOCA patients had an asymmetric pattern in the temporal areas with decreased blood flow in the right side only. Caudate hypoperfusion was found in ADCA I patients. Cerebral atrophy did not account for changes in regional blood flow, which probably indicate early involvement of cerebral structures.