Regione Puglia

To determine the prognostic significance of ambulatory blood pressure, we prospectively followed for up to 7.5 years (mean, 3.2) 1187 subjects with essential hypertension and 205 healthy normotensive control subjects who had baseline off-therapy 24-hour noninvasive ambulatory blood pressure monitoring. Prevalence of white coat hypertension, defined by an average daytime ambulatory blood pressure lower than 131/86 mm Hg in women and 136/87 mm Hg in men in clinically hypertensive subjects, was 19.2%. Cardiovascular morbidity, expressed as the number of combined fatal and nonfatal cardiovascular events per 100 patient-years, was 0.47 in the normotensive group, 0.49 in the white coat hypertension group, 1.79 in dippers with ambulatory hypertension, and 4.99 in nondippers with ambulatory hypertension. After adjustment for traditional risk markers for cardiovascular disease, morbidity did not differ between the normotensive and white coat hypertension groups (P = .83). Compared with the white coat hypertension group, cardiovascular morbidity increased in ambulatory hypertension in dippers (relative risk, 3.70; 95% confidence interval, 1.13 to 12.5), with a further increase of morbidity in nondippers (relative risk, 6.26; 95% confidence interval, 1.92 to 20.32). After adjustment for age, sex, diabetes, and echocardiographic left ventricular hypertrophy (relative risk versus subjects with normal left ventricular mass, 1.82; 95% confidence interval, 1.02 to 3.22), cardiovascular morbidity in ambulatory hypertension was higher (P = .0002) in nondippers than in dippers in women (relative risk, 6.79; 95% confidence interval, 2.45 to 18.82) but not in men (P = .91). Our findings suggest that ambulatory blood pressures stratifies cardiovascular risk in essential hypertension independent of clinic blood pressure and other traditional risk markers including echocardiographic left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

BACKGROUND: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

To cite this article: Brożek JL, Akl EA, Compalati E, Kreis J, Terracciano L, Fiocchi A, Ueffing E, Andrews J, Alonso-Coello P, Meerpohl JJ, Lang DM, Jaeschke R, Williams JW Jr, Phillips B, Lethaby A, Bossuyt P, Glasziou P, Helfand M, Watine J, Afilalo M, Welch V, Montedori A, Abraha I, Horvath AR, Bousquet J, Guyatt GH, Schünemann HJ, for the GRADE Working Group. Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 3 of 3. The GRADE approach to developing recommendations. Allergy 2011; 66: 588–595. This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients’ values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients’ values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.

Feasibility and effectiveness of a disease and care management model in the primary health care system for patients with heart failure and diabetes (Project Leonardo) Marco Matteo Ciccone1, Ambrogio Aquilino2, Francesca Cortese1, Pietro Scicchitano1, Marco Sassara1, Ernesto Mola3, Rodolfo Rollo4,Pasquale Caldarola5, Francesco Giorgino6, Vincenzo Pomo2, Francesco Bux21Section of Cardiovascular Disease, Department of Emergency and Organ Transplantation, School of Medicine, University of Bari, Bari, Italy; 2Agenzia Regionale Sanitaria – Regione Puglia (ARES), Apulia, Italy; 3ASL, Lecce, Italy; 4ASL, Brindisi, Italy; 5Cardiologia, Ospedale “Sarcone”, Terlizzi, Italy; 6Section of Endocrinology, Department of Emergency and Organ Transplantation, School of Medicine, University of Bari, Bari, ItalyPurpose: Project Leonardo represented a feasibility study to evaluate the impact of a disease and care management (D&CM) model and of the introduction of “care manager” nurses, trained in this specialized role, into the primary health care system. Patients and methods: Thirty care managers were placed into the offices of 83 general practitioners and family physicians in the Apulia Region of Italy with the purpose of creating a strong cooperative and collaborative “team” consisting of physicians, care managers, specialists, and patients. The central aim of the health team collaboration was to empower 1,160 patients living with cardiovascular disease (CVD), diabetes, heart failure, and/or at risk of cardiovascular disease (CVD risk) to take a more active role in their health. With the support of dedicated software for data collection and care management decision making, Project Leonardo implemented guidelines and recommendations for each condition aimed to improve patient health outcomes and promote appropriate resource utilization.Results: Results show that Leonardo was feasible and highly effective in increasing patient health knowledge, self-management skills, and readiness to make changes in health behaviors. Patient skill-building and ongoing monitoring by the health care team of diagnostic tests and services as well as treatment paths helped promote confidence and enhance safety of chronic patient management at home.Conclusion: Physicians, care managers, and patients showed unanimous agreement regarding the positive impact on patient health and self-management, and attributed the outcomes to the strong “partnership” between the care manager and the patient and the collaboration between the physician and the care manager. Future studies should consider the possibility of incorporating a patient empowerment model which considers the patient as the most important member of the health team and care managers as key health care collaborators able to enhance and support services to patients provided by physicians in the primary health care system.Keywords: partnerships, health team, patient empowerment, care coordination

ABSTRACT: The effectiveness of pre‐ and postharvest treatments with chitosan (0.1, 0.5, and 1.0%) to control Botrytis cinerea on table grapes was investigated. In postharvest treatments, small bunches dipped in chitosan solutions and inoculated with the pathogen showed a reduction of incidence, severity, and nesting of grey mold, in comparison with the control. Single berries artificially wounded, treated with the polymer, and inoculated with B. cinerea showed a reduced percentage of infected berries and lesion dia. Higher chitosan concentrations demonstrated greater decay reduction. All preharvest treatments significantly reduced the incidence of grey mold, as compared to the control. Table grapes treated with 1.0% chitosan showed a significant increase of phenylalanine ammonia‐lyase (PAL) activity. Consequently, besides a direct activity against B. cinerea , chitosan produces other effects contributing to reduce decay.

Anemia in oncology patients is often considered a side effect of cancer therapy; however, it may occur before any antineoplastic treatment (cancer-related anemia). This study was aimed to evaluate the prevalence of cancer-related anemia in a large cohort of oncology patients and whether inflammation and malnutrition were predictive of its development and severity. The present study included 888 patients with cancer at different sites between May 2011 and January 2014. Patients were assessed at diagnosis before any cancer treatment. The prevalence of anemia according to the main clinical factors (tumor site, stage and performance status) was analyzed. In each patient markers of inflammation, iron metabolism, malnutrition and oxidative stress as well as the modified Glasgow prognostic score, a combined index of malnutrition and inflammation, were assessed and their role in predicting hemoglobin level was evaluated. The percentage of anemic patients was 63% with the lowest hemoglobin levels being found in the patients with most advanced cancer and compromised performance status. Hemoglobin concentration differed by tumor site and was lowest in patients with ovarian cancer. Hemoglobin concentration was inversely correlated with inflammatory markers, hepcidin, ferritin, erythropoietin and reactive oxygen species, and positively correlated with leptin, albumin, cholesterol and antioxidant enzymes. In multivariate analysis, stage, interleukin-6 and leptin were independent predictors of hemoglobin concentration. Furthermore, hemoglobin was inversely dependent on modified Glasgow Prognostic Score. In conclusion, cancer-related anemia is a multifactorial problem with immune, nutritional and metabolic components that affect its severity. Only a detailed assessment of the pathogenesis of cancer-related anemia may enable clinicians to provide safe and effective individualized treatment.

PURPOSE: No randomized trials have been conducted to directly compare radiotherapy (RT) with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced squamous cell carcinoma of the head and neck. In this randomized trial, we compared these two treatment regimens in terms of compliance, toxicity, and efficacy. PATIENTS AND METHODS: Eligible patients were randomly assigned in a 1:1 ratio to receive either CDDP 40 mg/m(2) once per week or CTX 400 mg/m(2) as loading dose followed by CTX 250 mg/m(2) once per week concomitant to radical RT. For primary end points, compliance to treatment was defined as number of days of treatment discontinuation and drug dosage reduction. The acute toxicity rate was defined according to the National Cancer Institute Common Toxicity Criteria. Efficacy end points were local recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival. RESULTS: The study was discontinued early because of slow accrual after the enrollment of 70 patients. RT discontinuation for more than 10 days occurred in 13% of patients given CTX and 0% given CDDP (P = .05). Drug dosage reduction occurred in 34% given CTX and 53% given CDDP (difference not significant). Toxicity profiles differed between the two arms, with hematologic, renal, and GI toxicities more frequent in the CDDP arm, and cutaneous toxicity and the need for nutritional support more frequent in the CTX arm. Serious adverse events related to treatment, including four versus one toxic deaths, were higher in the CTX arm (19% v 3%, P = .044). Locoregional control, patterns of failure, and survivals were similar between the treatment arms. CONCLUSION: CTX concomitant to RT lowered compliance and increased acute toxicity rates. Efficacy outcomes were similar in both arms. These results raise the issue of appropriately selecting patients with head and neck cancer who can benefit from CTX in combination with RT.

Abstract A new, two‐step procedure is presented for determining the cation exchange capacity (CEC) of calcareous and gypsiferous soils. The method eliminates most of the errors inherent in conventional methods. The cation exchange sites are saturated with sodium by four successive “equilibrations” of the soil (4–5 g) with 33‐ml increments of a pH 8.2, 60% ethanol solution of 0.4N NaO Ac − 0.1 N NaCl (saturating solution). The saturated sample then is extracted with three 33‐ml increments of 1.0 N , pH 7 magnesium nitrate. Total sodium (Na t ) and chloride (Cl t ) are subsequently determined in the extracted solution. Chloride (Cl t ) is determined so that the soluble sodium (Na sol ), from the excess saturating solution carried over from the saturation step to the extraction step, may be deducted from the total sodium (Na t ) to obtain exchangeable sodium (Na exch ), which is equivalent to the CEC. Thus, CEC = Na exch = (Na t − Na sol ) = Na t − [Cl t (Na/Cl) saturating solution ] where (Na/Cl) saturating solution is the ratio of Na to Cl in the saturating solution.

Metabolites of pyrene and DNA adducts have been used as biomarkers of high level exposure to polycyclic aromatic hydrocarbons (PAHs). A systematic review was performed to evaluate whether these biomarkers are also valid markers of low level environmental exposure to PAHs. Thirty five studies were identified with more than 10 subjects that evaluated environmental air pollution to PAHs in relation to metabolites of PAHs, mainly hydroxypyrene (1-OHP), PAH-DNA adducts, or protein adducts. PAH metabolites and, to a less extent, PAH-DNA adducts correlated well at the group level with exposure to B(a)P even at low levels of air pollution. The use of these biomarkers should be more widely implemented in combination with more traditional techniques for the assessment of general population exposure to PAHs from ambient air pollution.

Letter to the Editor

This paper provides an introductory survey on the various systems that exploit magnetic fields for positioning. Such systems find applications in those scenarios, both indoors and outdoors, where global navigation satellite systems are not available or fail to provide information with the needed accuracy. While the main idea of using electromagnetic fields to provide position information dates back to the past century, new application-led research on this topic has emerged in recent years. Results have expanded the application range of magnetic positioning technologies and form now a domain of knowledge that enables realization of positioning systems applicable to indoor and outdoor environments. This paper provides the main characteristics of different positioning systems with focus on those solutions that are based on low-frequency magnetic fields. Some background theory is presented and positioning results from the literature are analyzed and compared.

OBJECTIVES: The recent emergence of new psychoactive compounds (novel psychoactive substances (NPS)) has raised prominent challenges in the fields of drug policy, substance use research, public health and service provision. The Recreational Drugs European Network project, funded by the European Commission, was implemented to improve the information stream to young people and professionals about effects/risks of NPS by identifying online products and disseminating relevant information through technological tools. METHODS: Regular multilingual qualitative assessments of websites, drugs fora and other online resources were carried out using the Google search engine in eight languages from collaborating countries. These included the following: the UK, Norway, Belgium, Germany, Hungary, Poland, Italy and Spain. Products were tested and prevention messages were developed and disseminated via technological tools such as interactive websites, SMS alert, social networking (Facebook, Twitter), Multimedia (You Tube), Smartphone applications (iPhone) and virtual learning environments (Second Life). RESULTS: The Recreational Drugs European Network project established itself as the first Europe-wide prevention programme designed for NPS based on the efficacy of novel information and communication technology-based forms of intervention. More than 650 NPS products and combinations were identified; relevant information was disseminated to target population and advice was given to both European Union/international agencies and national policy makers. CONCLUSIONS: Web-monitoring activities are essential for mapping the diffusion of NPS and the use of technological tools can be successfully incorporated in specific prevention programmes. Furthermore, the involvement of multi-disciplinary international partnerships was and continues to be fundamental for responding to such a prominent challenge.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

On the basis of the material available both in the scientific literature and on the web, this paper aims to provide a pharmacological, chemical and behavioural overview of the novel compound methoxetamine. This is a dissociative drug related to ketamine, with a much longer duration of action and intensity of effects. A critical discussion of the availability of information on the web of methoxetamine as a new recreational trend is here provided. Those methodological limitations, which are intrinsically associated with the analysis of online, non-peer reviewed, material, are here discussed as well. It is concluded that the online availability of information on novel psychoactive drugs, such as methoxethanine, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast-growing phenomenon.

BACKGROUND: Hypersensitivity reaction to nevirapine, which in some cases can be fatal, shows a higher prevalence in Sardinia in comparison with other Italian regions. OBJECTIVE: This study demonstrates that hypersensitive reaction to nevirapine in Sardinian HIV-infected patients is associated with the HLA Cw8-B14 haplotype. These two HLA class I antigens are in strong linkage disequilibrium in the Sardinian population. METHODS: Forty-nine Sardinian HIV-positive patients treated with nevirapine were studied. Thirteen (26%), developed a hypersensitive reaction thus requiring the drug to be discontinued. HLA class I and II molecular typing was performed in both nevirapine-hypersensitive and nevirapine-tolerant patients. To avoid biased representation of the allele frequencies in the two groups of treated patients, molecular typing was also performed in 82 HIV-positive patients who had not been treated with nevirapine. RESULTS: Considerable overlap was observed for the clinical, immunological and demographic characteristics of the 13 hypersensitive patients and 36 tolerant patients. Clinical parameters included viral load, status of HIV infection, CD4 and CD8 cell counts, hepatitis C virus/hepatitis B virus co-infections. Forty-six percent (6/13) of the nevirapine-hypersensitive subjects had the HLA-Cw8 and HLA-B14(65) antigens compared with 5% (2/36) of the nevirapine-tolerant group (P = 0.004; Pc = 0.05). CONCLUSION: In agreement with other recent reports, the utility of HLA typing in HIV patients to identify genetic factors that may confer susceptibility to drug-induced hypersensitive reaction was confirmed. A careful choice of antiretroviral therapy in susceptible individuals should significantly reduce the risk of severe hypersensitive reaction.

In the absence of any direct evidence, the relative importance of meat and dairy productions to Neolithic prehistoric Mediterranean communities has been extensively debated. Here, we combine lipid residue analysis of ceramic vessels with osteo-archaeological age-at-death analysis from 82 northern Mediterranean and Near Eastern sites dating from the seventh to fifth millennia BC to address this question. The findings show variable intensities in dairy and nondairy activities in the Mediterranean region with the slaughter profiles of domesticated ruminants mirroring the results of the organic residue analyses. The finding of milk residues in very early Neolithic pottery (seventh millennium BC) from both the east and west of the region contrasts with much lower intensities in sites of northern Greece, where pig bones are present in higher frequencies compared with other locations. In this region, the slaughter profiles of all domesticated ruminants suggest meat production predominated. Overall, it appears that milk or the by-products of milk was an important foodstuff, which may have contributed significantly to the spread of these cultural groups by providing a nourishing and sustainable product for early farming communities.

The possibility of extensive incorporation of soda-lime waste glass in the synthesis of fly ash-based geopolymers was investigated. Using waste glass as silica supplier avoids the use of water glass solution as chemical activator. The influence of the addition of waste glass on the microstructure and strength of fly ash-based geopolymers was studied through microstructural and mechanical characterization. Leaching analyses were also carried out. The samples were developed changing the SiO2/Al2O3 molar ratio and the molarity of the sodium hydroxide solution used as alkaline activator. The results suggest that increasing the amount of waste glass as well as increasing the molarity of the solution lead to the formation of zeolite crystalline phases and an improvement of the mechanical strength. Leaching results confirmed that the new geopolymers have the capability to immobilize heavy metal ions.

Patients with chronic lymphocytic leukemia (CLL) are at an increasing risk of infectious morbidity and mortality. Infections are generally due to bacteria and influenced by the degree of hypogammaglobulinemia; although, in more advanced stages of disease they may also be contributed by neutropenia due to bone marrow infiltration and/or cytotoxic therapy. Furthermore, defect in cell-mediated immunity appears to be a predisposing factor to infections in patients treated with newer purine analogues. Controversies surrounding the pathogenesis of infectious complications in CLL raise several questions on their management. Patients with advanced disease who receive cytotoxic therapy might qualify for antibacterial prophylaxis. Intravenous immunoglobulin (IVIG), although of scientific interest, may be of little relevance at the present time. The new growth factors should be tested in well-designed prospective studies.

Polymicrogyria is a malformation of cortical development that is often identified in children with epilepsy or delayed development. We investigated in vivo the potential of 7T imaging in characterizing polymicrogyria to determine whether additional features could be identified.