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.

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.

Prevalence of pancreatic disorders in HIV-infected hemophiliacs: diagnostic methods and their clinical significance.

Pancreatic damage has been well described in HIV+ patients and can occur both for therapy and opportunistic infections, but its prevalence is not clear. The aim of our study was to evaluate the prevalence of pancreatic damage in a cohort of HIV+ hemophiliacs together with the clinical and prognostic value of the diagnostic methods commonly used. We studied 75 HIV+ patients and 26 HIV- as a control group: they were evaluated by biochemical tests, indirect pancreatic functional tests, abdominal ultrasound (US) and computed tomography (CT). No differences were observed between HIV+ and HIV- in elevation of pancreatic enzymes. Eleven patients had slight CT alterations and none had abnormal US. In HIV+ there was no relationship between enzyme elevation and CDC group, CD4+ cell count or therapy. In conclusion, pancreatic disorders have a very low prevalence in HIV+ hemophiliacs and biochemical alterations we found had a doubtful clinical significance. Lipase and isoamylase are the more reliable tests and lipase, being the cheapest and easiest to perform, has to be considered as the first test of choice for monitoring pancreatic damage in HIV+ patients.

The design and use of a health status index for family physicians.

This paper describes a Health Status Index (HSI) which is part of a patient encounter form in a family practice center. The Index, which is used to profile a patient's health status longitudinally, combines physical and psychosocial measures of health. Based on its use in the center and through the presentation of data on patient health status, the authors illustrate how the Index can facilitate the evaluation of care and the management of practice. More specifically, they suggest that such data assist physicians in: (1) evaluating the effect of different modes of treatment on the duration and severity of ill-defined symptoms and complaints; (2) identifying high-risk patients for special attention; (3) indicating treatment modalities which produce more desirable outcomes; (4) determining the efficiency of different modes of treatment and of continued care; and (5) addressing chronological, as well as interpersonal and interprofessional, questions of providing continuous care for the chronically ill.

The use of computer generated patient profiles to evaluate resident performance in patient care.

This paper describes the way in which data from a computer-based health information system are used to review the service experiences of family practice residents. First, it discusses the development of the patient profiles that provide a chronological account of a patient's visits, their purposes, diagnoses, laboratory procedures, treatments, and outcomes. Then, through four cases, it describes the way in which these computer-generated displays are used by faculty to conduct concurrent reviews of residents' performances, to select medical records for review, and to initiate feedback and instruction to residents as they care for their patients.

[Effectiveness of piperacillin in childhood infections]. / Efficacia della piperacillina nelle infezioni dell'età pediatrica.

Piperacillin is a semisynthetic penicillin with a broad-spectrum: in particular it is active against Gram positive, Gram negative, aerobic and anaerobic bacteria often resistant to other antibiotics of the same group. We report a trial carried out on 38 children with severe and moderate infections treated with piperacillin. We have considered ESR, all leucocytes count and body temperature. No severe side effects have been reported. Piperacillin must be used as a first choice in pediatric age, mostly in case of mixed bacterial infections and in immunocompromised patients.

[Clinical evaluation of a new factor VIII concentrate in hemophilic children]. / Valutazione clinica di un nuovo concentrato di fattore VIII in bambini emofilici.

Studies of in vivo recovery, longevity and dose response of factor VIII following infusions of a new factor VIII concentrate (Koate, Cutter Laboratories) yielded results similar to those reported using other sources of factor VIII. Koate has been demonstrated to be clinically effective in classic hemophilia. This preparation was produced by refinements of the methods first described by Hershgold, Pool and Pappenhagen in 1966. By these procedures a high purity factor VIII concentrate is obtained being some 65 to 170 fold purified. This factor VIII concentrate was clinically evaluated in 11 hemophilic children (one of them with 7 Bethesda Units inhibitor) who received a total of 13 separate infusions. Biologic half-life values determined in two subjects resulted 12 and 9,5 hours comparing favorably with those previously reported. Initial 50% disappearance averaged 5,4 and 4,8 hours respectively. In vivo recovery of the infused factor VIII activity averaged 98 +/- 12,75%. Dose response measurements showed that 1 unit/Kg gave an in vivo increase in circulating activity of 1,97 +/- 0,93%.

[The prevention of liver disease in the hemophilic child]. / La prevenzione dell'epatopatia nel bambino emofilico.

The modern replacement therapy of inherited bleeding disorders has proved to be a major advance in the management of haemophilic children. However, the haemophiliacs, early treated with commercial clotting factor concentrates obtained from large amounts of plasma, are exposed to blood borne viruses responsible for post-transfusion hepatitis (PTH) and for their possible harmful long-term sequelae. Infact high prevalence of infection with hepatitis B virus, non-A, non-B agents, delta agent has been documented among haemophilic children. In this study we analyze the measures of surveillance at present available in order to reduce the risk of PTH in young haemophilic patients. Among these measures of prevention we point out the magnitude of administrating hepatitis B vaccine to susceptible children and of using antihaemophilic factor heat-treated to reduce infectivity in those children who have never been treated and without signs of active viral infections.

[Intra-familial transmission of HBV infection]. / La diffusione intrafamiliare dell'infezione da HBV.

We investigated 63 household contacts of 29 children positive for serologic markers of hepatitis B virus, in order to assess the intrafamiliar spread of HBV infection. 40 relatives of 15 children affected by chronic hepatitis B (Group I) and 23 relatives of 14 patients affected by hemophilia (Group II) were studied. HBV markers (HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe) were tested in all the subjects by RIA. Positive markers were found in 39 (62%) of the subjects; the combined prevalence for all HBV markers was 75% in the Group I, and 39% in the Group II. The higher prevalence rate in Group I can be explained by the possible previous infection of another member of the family, whereas in Group II the child is almost surely the first infected subject. Besides, subjects of Group I have probably been in contact with HBV infected children a longer time, compared to subjects in Group II. Our data suggest that household contacts of children with HBV infection are at high risk and should therefore be immunized against HBV.

[Thermographic monitoring of the evolution and therapy of chronic synovitis and cysts in hemophiliacs]. / Monitoraggio termografico dell'evoluzione e della terapia nella sinovite cronica e nella ciste degli emofili.

The authors have studied the evolution of chronic synovitis and of cysts in hemophilic patients, through measurement of the articular circumference or of the cyst. To obtain this, they have used a folding rule and liquid cristal strips, that have the characteristic, that they change colours from braunish to orange, from greenish to bluish according to the thermic gradient revealed. The authors have studied 21 hemophilic patients, affected from chronic synovitis for a total of 23 articulations and 5 patients with cyst. All patients have undergone several controls reporting dates revealed at 2,6 and 12 months from beginning of disease. The authors conclude, underlining the usefulness of this simple methodic that permits: - a reliable valutation of the therapeutic (profilatic) scheme applied to every single patient and gives a prognostic precision; - distinguishing, in fact, the recovery from the clinical recovery of the synovitis in order to avoid the appearance of unpleasant relapses.

[Chronic lead poisoning in childhood: clinical experience]. / L'intossicazione cronica da piombo in età pediatrica: esperienza clinica.

Since 1978, 818 children living near an industrial source of pollution have been screened for lead poisoning. Biochemical evidences of increased lead absorption have been found in 114 cases and in 62 of them it was of such degree to guarantee further investigations. Those 62 children received a thorough neuropsychologic evaluation revealing a significant reduction of IQ, learning difficulties, poor concentration and behavioral abnormalities. We also documented an increased rate of abnormal mathafases and breaks of chromatides in children with increased lead absorption compared with age and sex matched controls.

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.

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.

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.

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.