Characterization of circadian COPD symptoms by phenotype: Methodology of the STORICO observational study.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. The symptoms of COPD are troublesome, variable, can occur during all parts of the 24-h day and have a substantial impact on patients' health status, quality of life and healthcare resource utilization. Reducing symptoms, improving health status and increasing physical activity are major goals in the management of stable COPD. In order to provide effective, patient-oriented care, patients should be evaluated on the basis of lung function, frequency of symptoms and patient-perceived impact of symptoms on their lives and treatment decisions made on a case-by-case basis. The identification of COPD phenotypes is an evolving debate and literature data about the circadian variation of COPD symptoms according to phenotypes are nowadays lacking. The ongoing STORICO (STudio Osservazionale sulla caratteRizzazione dei sIntomi delle 24 ore nei pazienti con BPCO) study (NCT03105999) is aimed to describe by clinically defined phenotypes the frequency and 12-month evolution of early-morning, day- and night-time COPD symptoms in a cohort of 600 Italian patients with stable COPD. Secondary objectives include the description of the 12-month variation of outcomes of interest according to phenotypes and of the healthcare resources utilization (overall and by phenotype) during 12-month observation. An exploratory analysis will be conducted aimed to phenotype COPD patients in an alternative researcher-independent way based on circadian pattern of symptoms combined with measures of respiratory function, health-related quality of life and comorbidity. The present paper describes the methodology of the STORICO study.

Prevalence and associated features of self-reported freezing of gait in Parkinson disease: The DEEP FOG study.

Freezing of Gait (FOG) is a common and disabling symptom in patients with Parkinson disease (PD). The relationship between FOG and dopaminergic medication is complex. The aim of the present study was to estimate the prevalence of self-reported FOG, its associated clinical features, and its relationship with wearing-off in a wide PD population. This is an observational multicenter study of 634 consecutive non-demented PD patients. Patients were identified either as freezers or non-freezers based on item-3 of the Freezing of Gait-Questionnaire. FOG was then classified as on, off and onoff freezing based on its relationship with wearing-off. Patients were assessed with Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale, 8-item Parkinson's disease Questionnaire, Mini-Mental State Examination. Data from 593 patients were analyzed, 325 (54.3%) were freezers of whom 200 (61.6%) experienced FOG only during off state (off-freezers), 6 (1.8%) only during on state and 119 (36.6%) either in on and off states or independently of dopaminergic response-related symptoms (onoff-freezers). Overall, freezers vs non-freezers had longer disease duration, more advanced disease and greater disability. Moreover, freezers more frequently reported wearing-off and experienced worse quality of life. Onoff-freezers vs off-freezers were older, more severely disabled, less likely to experience wearing-off, treated with lower levodopa equivalent daily dose and with poorer cognitive performance. Self-reported FOG is mainly recognizable in advanced PD and is associated with more disability and worse quality of life. Onoff-FOG may represent the result of under-treatment or rather interpretable as a distinct clinical entity.

Exercise training provides cardioprotection via a reduction in reactive oxygen species in rats submitted to myocardial infarction induced by isoproterenol.

Exercise training has demonstrated cardioprotection effects. However, the exact mechanism behind this effect is not is clear. The present study evaluated the effects of 12 weeks of previous treadmill training on the levels of oxidative damage, antioxidant enzyme activity and injury in the myocardium of rats submitted to infarction induced by isoproterenol (ISO). Isoproterenol treatment (80 mg/kg given over 2 days in two equal doses) caused arrhythmias and 60% mortality within 24 h of the last injection in the control group (C + ISO) group when compared with the saline control group (saline). Creatine Kinase--MB levels were markedly increased in hearts from ISO-treated animals in the C + ISO group. Twelve weeks of treadmill training reduced superoxide production, lipid peroxidation levels and protein carbonylation in these animals, as well as increasing the activities and expressions of SOD and CAT. Previous training also reduced CK-MB levels and numbers of deaths by 40%, preventing the deleterious effects of ISO. Based on the data obtained in this study, it is suggested that 12-week treadmill training increases antioxidant enzymes, decreases oxidative damage and reduces the degree of infarction induced by ISO in the hearts of male rats.

Anhedonia and cognitive impairment in Parkinson's disease: Italian validation of the Snaith-Hamilton Pleasure Scale and its application in the clinical routine practice during the PRIAMO study.

OBJECTIVE: To assess the psychometric properties of the Italian version of the Snaith-Hamilton Pleasure Scale (SHAPS) and to study the relationship between anhedonia, depression and cognitive impairment in patients with Parkinson's disease (PD). METHODS: The SHAPS (14 items) was translated into Italian and pre-tested in a pilot study. Two items evaluating physical anhedonia related to sexual issues were added. The Italian version of SHAPS was validated in 274 consecutive PD patients, divided into patients with major depression according to DSM-IV criteria (dPD) and patients without depression (nPD), and in healthy subjects. To test the feasibility of the instrument and to determine whether clinical data affect anhedonia, we also administered SHAPS to 1307 patients with different types of parkinsonism. RESULTS: The Italian SHAPS proved to be easy to understand as regards the question and answer modes. Intraclass coefficient for test-retest reliability was 0.65 for the total score. KR index was 0.61. ANOVA of the SHAPS total score revealed that scores were higher in dPD patients than in healthy controls and nPD (p<0.05). In the 1307 patients with various types of parkinsonism, the SHAPS data showed that anhedonia was related to age, type of parkinsonism, apathy, depression and cognitive impairment. Anhedonia was correlated with frontal dysfunctions in supranuclear palsy and PD patients (r=-0.682 and -0.264 respectively, p<0.05). CONCLUSION: The Italian version of the SHAPS is a reliable tool with which to assess anhedonia in patients with PD and other forms of parkinsonism.

Antithrombin plasma levels decrease is associated with preeclampsia worsening.

Antithrombin plasma levels (AT) have been found decreased in women with preeclampsia (PE), but little is known about the trend of AT during the course of this disease. We prospectively investigated AT in consecutive women admitted to our hospital with a diagnosis of PE, to assess if AT fluctuations could be associated with the evolution of the disease. AT, platelet count and D-dimer levels were determined every other day. In the 73 patients studied, AT, platelet count and fibrinogen progressively reduced during the observational period, reaching a nadir on the day of delivery, whereas D-dimer progressively increased over time. Statistical analysis was restricted to the 39 women that had an AT measurement performed on each of days -1, 0 and +1, with respect to the day of delivery. These subjects showed a significant decrease in AT on the day of delivery compared to the day just before (77.8 +/- 15.1%vs. 85.4 +/- 14.2%, P = 0.027), followed by a recovery on the first day after delivery (87.6 +/- 21.3% from 77.8 +/- 15.1%, P = 0.005). Our study demonstrates that a significant drop in AT levels is associated with the clinical worsening of PE, regardless of its severity.

Psychological distress and coping strategies in patients with psoriasis: the PSYCHAE Study.

OBJECTIVE: Our objectives were to determine the prevalence of psychological distress in a large sample of Italian patients with psoriasis; to establish whether disease severity and psychological distress are associated; to identify the strategies employed to cope with psoriasis; to evaluate the coping strategies employed by dermatologists; and to identify potential predictors of psychological distress. DESIGN: Cross-sectional. SETTING: Thirty-nine Italian dermatology centres. SUBJECTS: One thousand five hundred and eighty (1580) patients with psoriasis. METHODS: Minor psychological distress was evaluated using the General Health Questionnaire-12 (GHQ-12) and major psychopathological distress using the Brief Symptom Inventory (BSI); coping strategies were evaluated using the Brief COPE questionnaire; disease severity was evaluated using the body surface area index. RESULTS: Patients were aged 44 +/- 13 years (mean +/- SD) and were mainly men (57%). Minor psychological distress was present in 46% of patients and major psychopathological distress in 11% of them. Both minor (54% vs. 40%, P < 0.0001) and major (17% vs. 7%, P < 0.0001) distress were more frequent in women than in men. The psychological status of women was worse than that of men independently from the extension of psoriasis. There was no association between the presence of distress and the treatment prescribed by dermatologists. Planning and active coping were the strategies most commonly employed by patients to cope with psoriasis, but there were between-gender differences. Most dermatologists employed a 'problem-orientated' attitude in caring for patients. CONCLUSIONS: (i) Psychological distress was relatively frequent in our patients with psoriasis; (ii) female gender was the most important predictive factor for psychological distress; (iii) there was no association between psoriasis severity and psychological distress; (iv) planning and active coping were the coping strategies most frequently employed by patients; and (v) most dermatologists employed a problem-orientated attitude in caring for patients.

Agreement between oncology guidelines and clinical practice in Italy: the 'right' program. A project of the Italian Association of Medical Oncology (AIOM).

BACKGROUND: RIGHT (Research for the Identification of the most effective and hIGhly accepted clinical guidelines for the cancer Treatment) is a project promoted by the Italian Association of Medical Oncology (AIOM) to measure the concordance between oncology guidelines and clinical practice. The goal of this pilot phase was to develop and test a reliable process to measure this concordance nationwide. MATERIALS AND METHODS: Twenty Italian centers participated to the survey. Breast cancer (BC) and colorectal cancer (CRC): guidelines issued by AIOM in 2003 were selected. A total of 29 indicators linked to the process of care were abstracted. Patients who had their first visit at the oncology center between February 2004 and June 2005, with a diagnosis of invasive BC (stage 1 or 2), colon cancer (stage 3), rectal cancer (stage T3-4 or N1-2) or advanced CRC were enclosed. RESULTS AND CONCLUSION: One hundred and sixty-one patients (80%) were analyzed. On average, 93% of BC and 80.3% of colorectal patients received recommended care. These first results indicate that the RIGHT system provides a valid measurement of oncology care to assess agreement with guidelines. A second larger phase of this nationwide monitoring program will enable results to be generalized.

Elevated plasma levels of factor VIII in women with early recurrent miscarriage.

AIMS: Inherited and acquired thrombophilia have been found to be associated with recurrent pregnancy loss. This paper examines whether or not elevated factor (F)VIII:C plasma levels, which have been demonstrated to be an independent risk factor for venous thromboembolism, are a risk factor for early recurrent miscarriages also. PATIENTS AND METHODS: Consecutive women referred to our clinic with a history of early recurrent abortion (at least three pregnancy losses before week 13 of gestation) were eligible for the study. Exclusion criteria were endocrine, immunological, anatomical and genetic causes of embryo demise, as well as any thrombophilic abnormality, either congenital or acquired, or a personal or familial history of venous thromboembolism. FVIII:C plasma levels were determined in 51 cases and in 51 controls matched for age, ethnicity and blood group. RESULTS: The mean FVIII:C level in the control subjects was 106.8 IU dL-1, compared with 128.2 IU dL-1 in the patients group (P = 0.0002). Thirteen (25.5%) of the 51 patients had FVIII:C values exceeding the 90th centile of the control population (145 IU dL-1), compared with four subjects in the control group (chi2 = 4.52; P = 0.033; odds ratio = 4.02, 95% confidence interval 1.09, 16.05). No cases with increase in FVIII:C levels attributable to an acute-phase reaction, as assessed by C-reactive protein plasma concentration, were found. CONCLUSIONS: We found FVIII:C levels significantly higher in women with early recurrent miscarriage compared with controls. This finding suggests a possible association between this thrombophilic condition and early reproductive failures.

A simple and safe nomogram for the management of oral anticoagulation prior to minor surgery.

In 80 consecutive, anticoagulated patients scheduled for minor surgery, we reduced warfarin daily dosage by 50% on days 4, 3 and 2 before the surgery, restoring the original dose the day immediately before surgery. The evening after surgery, patients took a double warfarin dose, and then the usual maintenance dose was reintroduced. The mean International Normalized Ratio (INR) value assessed 1 week before surgery was 2.63 (range 1.88-3.87); it decreased at the moment of performing surgery to 1.68 (range 1.42-2.20; P < 0.05 with respect to the preoperative value), and returned to 2.43 7 days after (range 1.96-3.51, P = ns with respect to the preoperative value). No significant difference was found comparing prothrombin fragment 1.2 (F1.2) levels 1 week before surgery and on the morning of surgery (0.49 ng/ml vs 0.67 ng/ml, P = ns), suggesting that no activation of blood coagulation had taken place following the reduction of anticoagulant therapy. Patients developed neither major nor minor bleeding, nor thromboembolism during the procedures or up to 1 month after surgery. In our experience, this method for the management of anticoagulation before minor surgery has been shown to be safe and useful, avoiding the cumbersome shift to either intravenous or subcutaneous heparin.

Genetic characterization of the body attributed to the evangelist Luke.

Historical sources indicate that the evangelist Luke was born in Syria, died in Greece, and then his body was transferred to Constantinople, and from there to Padua, Italy. To understand whether there is any biological evidence supporting a Syrian origin of the Padua body traditionally attributed to Luke, or a replacement in Greece or Turkey, the mtDNA was extracted from two teeth and its control region was cloned and typed. The sequence determined in multiple clones is an uncommon variant of a set of alleles that are common in the Mediterranean region. We also collected and typed modern samples from Syria and Greece. By comparison with these population samples, and with samples from Anatolia that were already available in the literature, we could reject the hypothesis that the body belonged to a Greek, rather than a Syrian, individual. However, the probability of an origin in the area of modern Turkey was only insignificantly lower than the probability of a Syrian origin. The genetic evidence is therefore compatible with the possibility that the body comes from Syria, but also with its replacement in Constantinople.

Bedside assessment of respiratory viscoelastic properties in ventilated patients.

Viscoelasticity represents an important component of respiratory mechanics, being responsible, in some cases, for most of the pressure dissipated during breathing. Hitherto the methods available for determining the viscoelastic properties have been simplified, but are still time-demanding and depend on a great deal of calculation. In this study, a simple means of determining respiratory viscoelastic properties during mechanical ventilation was introduced. The viscoelastic constants of the respiratory system, modelled as a Maxwell body, were studied in 17 normal subjects and seven patients with acute lung injury (ALI) using two end-inspiratory occlusions; one with a short inspiratory time (tI) to determine the elastic component of viscoelasticity and the other with a long tI to assess the resistive component of viscoelasticity. The results were reproducible and similar to those provided by the previously described multiple-breath method (MB). The mean+/-SD viscoelastic resistance was 5.31+/-1.50 cm H2O x L(-1) x s with the proposed method and 5.71+/-1.87 cm H2O x L(-1) x s with the MB method in normal subjects, and 8.93+/-2.82 cm H2O x L(-1) x s and 10.36+/-3.13 cm H2O x L(-1), respectively in ALI patients. The mean+/-SD viscoelastic elastance was 3.92+/-0.84 cm H2O x L(-1) and 4.94+/-1.01 cm H2O x L(-1) in normal subjects and 7.08+/-2.01 cm H2O x L(-1) and 8.21+/-1.16 cm H2O x L(-1) in ALI patients, respectively. The mean+/-SD viscoelastic time constant was 1.36+/-0.24 s and 1.17+/-0.34 s in normal subjects and 1.26+/-0.35 s and 1.24+/-0.23 in ALI patients, respectively. The method was easy to perform and applicable at the bedside in clinical routine.

Genetic structure of Quechua-speakers of the Central Andes and geographic patterns of gene frequencies in South Amerindian populations.

A sample of 141 Quechua-speaking individuals of the population of Tayacaja, in the Peruvian Central Andes, was typed for the following 16 genetic systems: ABO, Rh, MNSs, P, Duffy, AcP1, EsD, GLOI, PGM1, AK, 6-PGD, Hp, Gc, Pi, C3, and Bf. The genetic structure of the population was analyzed in relation to the allele frequencies available for other South Amerindian populations, using a combination of multivariate and multivariable techniques. Spatial autocorrelation analysis was performed independently for 13 alleles to identify patterns of gene flow in South America as a whole and in more specific geographic regions. We found a longitudinal cline for the AcP1*a and EsD*1 alleles which we interpreted as the result of an ancient longitudinal expansion of a putative ancestral population of modern Amerindians. Monmonnier's algorithm, used to identify areas of sharp genetic discontinuity, suggested a clear east-west differentiation of native South American populations, which was confirmed by analysis of the distribution of genetic distances. We suggest that this pattern of genetic structures is the consequence of the independent peopling of western and eastern South America or to low levels of gene flow between these regions, related to different environmental and demographic histories.

Geographic patterns of mtDNA diversity in Europe.

Genetic diversity in Europe has been interpreted as a reflection of phenomena occurring during the Paleolithic ( approximately 45,000 years before the present [BP]), Mesolithic ( approximately 18,000 years BP), and Neolithic ( approximately 10,000 years BP) periods. A crucial role of the Neolithic demographic transition is supported by the analysis of most nuclear loci, but the interpretation of mtDNA evidence is controversial. More than 2,600 sequences of the first hypervariable mitochondrial control region were analyzed for geographic patterns in samples from Europe, the Near East, and the Caucasus. Two autocorrelation statistics were used, one based on allele-frequency differences between samples and the other based on both sequence and frequency differences between alleles. In the global analysis, limited geographic patterning was observed, which could largely be attributed to a marked difference between the Saami and all other populations. The distribution of the zones of highest mitochondrial variation (genetic boundaries) confirmed that the Saami are sharply differentiated from an otherwise rather homogeneous set of European samples. However, an area of significant clinal variation was identified around the Mediterranean Sea (and not in the north), even though the differences between northern and southern populations were insignificant. Both a Paleolithic expansion and the Neolithic demic diffusion of farmers could have determined a longitudinal cline of mtDNA diversity. However, additional phenomena must be considered in both models, to account both for the north-south differences and for the greater geographic scope of clinical patterns at nuclear loci. Conversely, two predicted consequences of models of Mesolithic reexpansion from glacial refugia were not observed in the present study.

Patterns of gene flow inferred from genetic distances in the Mediterranean region.

The analysis of population structure may lead to inferences about demographic phenomena. In particular, regions of sharp genetic differentiation suggest the existence of factors that impaired gene flow and increased the evolutionary role of genetic drift. Here, we present an analysis of a data set of 10 allele frequencies in 39 populations of the Mediterranean region. As a preliminary step, we describe spatial patterns of allele frequencies using spatial autocorrelation analysis. We then construct a network connecting localities and estimate genetic distances along the edges of the network. By applying specific algorithms, we locate on the map the areas of sharpest genetic differentiation, or genetic boundaries. The main boundaries separate the northern and the southern coasts, especially in their western portions; in addition, several localities appear genetically isolated. The comparatively high genetic differentiation across the western Mediterranean, where the sea distances between localities are shorter, strongly suggests that the sea distance by itself can hardly be regarded as a major isolating factor among these populations. On the contrary, the decrease in genetic resemblance between populations of the 2 coasts as one proceeds westward may reflect an increased genetic exchange in the eastern Mediterranean basin or independent human dispersal along the 2 coasts or both.

Single-breath method for assessing the viscoelastic properties of the respiratory system.

In order to explain the time dependency of resistance and elastance of the respiratory system, a linear viscoelastic model (Maxwell body) has been proposed. In this model the maximal viscoelastic pressure (Pvisc.max) developed within the tissues of the lung and chest wall at the end of a constant-flow (V') inflation of a given time (tI) is given by: Pvisc,max = R2V'(1-e(-tI/tau2), where R2 and tau2 are, respectively, the resistance and time constant of the Maxwell body. After rapid airway occlusion at t1, tracheal pressure (Ptr) decays according to the following function: Ptr(t) = Pvisc(t) + Prs,st = Pvisc,max(etocc/tau2)+ Prs,st, where tocc/is time after occlusion and Prs,st is static re-coil pressure of the respiratory system. By fitting Ptr after occlusion to this equation, tau2 and Pvisc,max are obtained. Using these values, together with the V' and tI pertaining to the constant-flow inflation preceding the occlusion, R2 can be calculated from the former equation. Thus, from a single breath, the constants tau2, R2 and E2 (R2/tau2) can be obtained. This method was used in 10 normal anaesthetized, paralysed, mechanically ventilated subjects and six patients with acute lung injury. The results were reproducible in repeated tests and similar to those obtained from the same subjects and patients with the time-consuming isoflow, multiple-breath method described previously.