Long-term treatment with low-dose medicine in chronic childhood eczema: a double-blind two-stage randomized control trial.

BACKGROUND: The efficacy of low-dose medicine (LDM) in childhood mild/moderate eczema is not known. We conducted a double-blind, two-stage, randomized, placebo-controlled clinical trial, lasting 23 months, to address this issue. METHOD: Eighty children with chronic mild/moderate eczema were randomly allocated to Group A (placebo) or Group B (treatment group; Galium-Heel®, a low-dose multicomponent medicine based upon natural substances; Guna-Interleukin 12 and Guna-Interferon-γ administered twice a day for six non-consecutive months for each stage). LDM is characterized by the use of biological molecules, such as cytokines, neuropeptides, growth factors, hormones at very low concentrations, which correspond to physiological levels within the human body. The dosage of the cytokines used in this trial (IFN-γ and IL-12) is 10 fg/ml. The SCORAD index was evaluated by the same operator: subjects with a SCORAD index below 20 were considered to have mild eczema (61/80; mean: 10.79), whereas a SCORAD index between 20-50 indicated moderate eczema (19/80; mean: 26.84). The data of 66/80 children were analyzed in stage 1 and those of 62/66 children in stage 2. The primary outcome measure was reduction of eczema severity assessed by the SCORAD index. Secondary outcomes were disease-free interval, and treatment safety and tolerability. RESULTS: The decrease in disease severity was greater in Group B than in Group A already in stage 1 (a decrease 63.9% versus 53.2%), but the difference was not significant (p = 0.16). Moreover, subjective symptoms (itching and sleep disturbances) initially decreased and then worsened in Group A, whereas itching decreased linearly and sleep disturbances decreased significantly (p=0.049) in Group B. CONCLUSIONS: Preliminary evidence suggests potential benefit, but further work is needed to validate this approach. TRIAL REGISTRATION: The trial was registered with EudraCT number 2010-018640-13 through the database of the National Clinical Trials Monitoring Centre Database (Osservatorio delle Sperimentazioni Cliniche, OsSC) of the Italian Medicines Agency.

Therapeutic management and costs of severe haemophilia A patients with inhibitors in Italy.

Haemophilia A (HA) patients with high responding inhibitors require therapies with bypassing agents to control bleedings or Immune Tolerance Induction (ITI) to attempt inhibitor eradication and restore FVIII therapy. The aim of this study was to assess the therapeutic management and product consumption of HA inhibitor patients and the relative costs in Italy. A retrospective survey was performed utilizing data from the National Registry of Congenital Coagulopathies and from a specific questionnaire on product consumption of HA inhibitor patients over the year 2011. Among HA patients, 10% had currently detectable inhibitors; 24% of patients were undergoing ITI (mostly children) and 76% utilized bypassing agents. Patients on ITI consumed 45,000,000 IU of FVIII (median consumption/patient of 1,200,000 IU year(-1)). Patients receiving bypassing agents utilized 21,000,000 IU of aPCC (median consumption/patient of 360,000 IU year(-1)), and 38,000 mg of rFVIIa (median consumption/patient of 440 mg year(-1)). The annual cost/patient on ITI and on bypassing agents therapy was analysed. Recombinant products represented the product of choice for children therapies in >90% of the cases. FVIII prophylaxis of severe HA patients without inhibitor costs about half than therapy with bypassing agents and is three times less expensive than prophylaxis with such agents. Therefore, the possibility to restore FVIII prophylaxis, having eradicated the inhibitor through ITI, can justify the high costs of ITI treatment needed in the short term. Consistent with this notion, over the last years a 50% increase in the number of patients undergoing ITI in Italy was registered.

Models for institutional and professional accreditation of haemophilia centres in Italy.

The Health Commission of the Conference between the Italian State and Regions recognized the need to establish an institutional accreditation model for Haemophilia Centres (HCs) to be implemented by 21 Regions in order to provide patients with haemophilia and allied inherited coagulations disorders with high and uniform standards of care. The Italian National Blood Centre, on behalf of the Commission, convened a panel of clinicians, patients, experts, representatives from Regions and Ministry of Health. The agreed methodology included: systematic literature review and best practice collection, analysis of provisions and regulations of currently available services, priority setting, definition of principles and criteria for the development of recommendations on the optimal requirements for HCs. The result was the formulation of two recommendations sets. Two sets of recommendations were produced. The first concerns regional policy planning, in which the following aspects of comprehensive haemophilia care should be considered for implementation: monitoring and auditing, multidisciplinary approach to clinical care, protocols for emergency management, home treatment and its monitoring, patient registries, drug availability and procurement, recruitment and training of health care professionals. The second set concerns the accreditation process and lists 23 organizational requirements for level 1 HCs and 4 additional requirements for level 2 HCs. These recommendations help to provide Italian Regional Health Authorities with an organizational framework for the provision of comprehensive care to patients with inherited coagulation disorders based on current scientific evidence.

ISSQoL: a new questionnaire for evaluating the quality of life of people living with HIV in the HAART era.

OBJECTIVE: To design a Health-related Quality of Life (HRQoL) instrument for HIV-infected people in the era of highly active antiretroviral therapy (HAART). METHODS: The self-administered questionnaire was developed by an Italian network including researchers, physicians, people living with HIV, national institutions and community-based organizations (CBO) through several steps: (1) review of existing HRQoL literature and questionnaires for HIV-infected people; (2) selection of relevant domains measuring HRQoL in HIV-infected people, and identification of new domains related to new aspects of HRQoL concerning HAART-treated individuals; (3) conduction of two pre-test analyses in independent groups of Italian HIV-positive people (n approximately =100) distributed throughout the country. The objectives of the first pre-test were to verify the usefulness of the questionnaire, to construct a form easily understandable by everyone, to define the domains and their significance; the second pre-test aimed at evaluating and reshaping the questionnaire based on a statistical analysis of the outcomes of first pre-test; (4) validation analysis. A large cohort of people with HIV infection was recruited for the last step. RESULTS: The internal consistence reliability (Cronbach's alpha) was >or=0.70 for all domains. Most domains had Cronbach's coefficient >0.80. All domains demonstrated convergent and discriminant validity. The final version of ISSQoL includes two sections: HRQoL Core Evaluation Form (9 domains) and Additional Important Areas for HRQoL (6 domains). The ISSQoL was administered together with two additional forms: a Daily Impact of Symptoms Form and a Demographic Information Form. The Additional Important Areas for HRQoL include social support, interaction with medical staff, treatment impact, body changes, life planning, and motherhood/fatherhood. CONCLUSION: The data reported in the present paper provide preliminary evidence of the reliability and validity of the ISSQoL questionnaire for the measurement of HRQoL in HIV-infected people. The direct involvement of HIV-positive people in all the phases of the project was a key aspect of our work.

Assessment of the diet of 0- to 6-year-old children in municipal schools in a Brazilian city.

Diet control is one of the important factors in the prevention of dental caries because food functions as substratum for fermentation and, consequently, for the formation of the organic acids that demineralize the tooth surface. This study aims to descriptively assess school diet and the associated caries-preventive methods applied to children in all municipal nursery schools of a Brazilian city (Aragatuba/SP). For this, a questionnaire with open and closed questions was used. The results showed that all schools serve school meal, which is composed mainly of sugar, carbohydrates, and proteins. The students enjoy the meal very much because for most of them, the meal served at school is the only source of food. It was observed that 90% of the schools offer other kinds of food besides the main school meal. The snacks served such as cakes, white hominy, and milk fudge are composed of sweet and highly cariogenic foods. It was also verified that in 13.30% of the schools, the daily supervised dental hygiene, an important procedure that should not be neglected, is not carried out. This procedure introduces the children to healthy habits that are added to those acquired in the family environment. It was concluded that the school diet is potentially cariogenic and, in association with the lack of daily dental hygiene, this potential may become even higher.

Subepithelial infiltrates associated to viral keratoconjunctivitis following photorefractive keratectomy.

PURPOSE: To report three cases of adenoviral keratoconjunctivitis in patients who have undergone photorefractive keratectomy and that just developed subepithelial infiltrates. METHODS: Description of patients that developed postoperative adenoviral keratoconjunctivitis after photorefractive keratectomy without influence in the final visual outcome. RESULTS: All patients presented adenoviral keratoconjunctivitis 2-3 months after refractive surgery. They developed multiple pinpoint subepithelial infiltrates in six eyes, without haze development. The final uncorrected visual acuity was better or equal to 20/30. CONCLUSION: Although patients undergoing photorefractive keratectomy might develop severe corneal scarring following ocular infections, such events may follow their natural evolution.

Bilateral endogenous endophthalmitis associated with infective endocarditis: case report.

Bilateral endogenous endophthalmitis is a rare condition initiated by infection by microbes in the bloodstream, such as those arising from a foci of infective endocarditis. We report a case and discuss the diagnostic aspects and the clinical outcome of a patient with characteristic findings of the disease. The patient was a 49 year old white male who had a metallic aortic valve implanted 7 months previously, and who presented to the hospital with 10 days of fever, cough and dyspnea, then diarrhea and mental confusion. On the second day of hospitalization, he experienced sudden loss of vision in both eyes. A Gram-positive coccobacillus was isolated from the bloodstream, he was treated with fluoroquinolone with disappearance of fever, decreased ocular inflammation, and improvement in his vision to light perception. He later underwent valve replacement surgery but died during the procedure. We review the occurrence of ocular signs and symptoms and their importance in patients with endocarditis.

Survival of patients with blood-borne AIDS in Italy.

BACKGROUND: AIDS represents an important public health problem in Italy. Long-term health care policy planning requires knowledge about the variability of the risk of mortality. The AIDS Surveillance Registry (RAIDS), maintained by the AIDS Operational Centre (COA) of the National Health Institute of Italy, provides valuable information to study the determinants of survival after diagnosis with AIDS. This study aimed to estimate the trends among people infected by the human immunodeficiency virus (HIV) through blood-related products. METHODS: Study subjects were 595 persons with AIDS whose sole ascertained risk factors were either blood transfusions or plasma-concentrate infusions, diagnosed from the beginning of the epidemic in 1985 through June 1995 and reported to RAIDS by the end of June 1996. The Kaplan-Meier technique was used to estimate the survival distribution; log-rank and Wilcoxon tests were both performed to assess the effects of demographic and clinical factors. Cox proportional hazards models were used to identify those factors independently and significantly associated with death: model building and fitting were performed in a stepwise fashion, by using the score and martingale residuals, based on a new class of graphical and numerical methods developed recently for checking the assumptions underlying the model. RESULTS AND CONCLUSIONS: In Italy the median survival time for AIDS patients infected by contaminated blood, was estimated to be 12.7 months. In univariate analyses it was found that women, younger patients (age < 35) and those diagnosed more recently with a higher value of CD4 cell counts (>37 cells m(-3)) have better survival. Patients diagnosed with AIDS-associated neurological disease (neuro-AIDS), or lymphoma, had a median survival significantly shorter. Patients diagnosed in the south of Italy tend to have a survival time shorter than patients diagnosed in the north. In a multivariate time-dependent regression analysis, only type of AIDS indicator disease, age and calendar time of diagnosis proved to be significant prognostic factors. It was not possible to estimate the effect of risk category (haemophiliacs versus transfused) due to the lack of proportionality in the estimated hazard. In conclusion, survival time is found to improve over time, indicating a likely positive effect of better care in treating HIV and AIDS patients.

Regional survival differences across Europe in HIV-positive people: the EuroSIDA study.

OBJECTIVES: To analyse the survival differences between macro-regions of Europe (northern, central and southern Europe) between 1994 and early 1999, and their possible association with antiretroviral treatment differences. DESIGN: From September 1994 the EuroSIDA study has prospectively followed non-selected HIV-infected people from 50 clinical sites in 18 European countries (n = 7331). METHODS: Cox proportional hazards models were used to compare death rates between regions and to investigate the relationship between treatment usage and regional mortality rates. Kaplan-Meier curves were used to compare survival from the first CD4 lymphocyte count of < 200 x 10(6)/l or < 50 x 10(6)/l. RESULTS: At the time of analysis, the median follow-up was 21 months and there was a total of 1544 deaths. In people with a CD4+ cell count that fell below 200 or 50 x 10(6)/l those from central Europe had a better prognosis compared with those from the two other regions (P < 0.05). Patients from central Europe were more frequently exposed to reverse transcriptase inhibitors and protease inhibitors compared with patients from other regions (P < 0.001). There was a significant difference in risk of death between regions after adjustment for baseline differences in demography, presence of AIDS and level of immunodeficiency (risk of death in central Europe was 37% lower than that in southern Europe (P < 0.0001) and 33% lower than in northern Europe (P < 0.0001)). After adjustment for use of individual antiretroviral agents, intensity of treatment regimen, CD4 lymphocyte count, weight, haemoglobin and development of AIDS as time-dependent covariates, the differences became much smaller (risk in central Europe 13% lower than that in southern Europe (P = 0.071) and 15% lower than in northern Europe (P = 0.054). CONCLUSION: Antiretroviral therapy has been used more aggressively in Europe in recent years, resulting in improved prognosis. In this study we observed that the HIV mortality rate in central Europe was significantly lower than those in northern and southern Europe in the period 1994 to early 1999. This finding appears to be due to the effect on survival of different treatment policies and drug availability in the three regions of Europe during this time period, with central European countries, on average, having introduced more aggressive treatment strategies earlier.

Direct detection of Clostridium perfringens enterotoxin in patients' stools during an outbreak of food poisoning.

An outbreak of diarrhoea in a hotel affected 25 time keepers attending the 1997 Mediterranean Games. Epidemiological investigation implicated a 'pasta al ragù' consumed at the hotel's restaurant and Clostridium perfringens food poisoning was identified by direct detection of C. perfringens enterotoxin in patients' stools. This report confirms that a careful evaluation of epidemiological features, together with the availability of direct and rapid laboratory methods, may lead to a prompt identification of C. perfringens food poisoning.

The impact of antiviral therapy with zidovudine: a retrospective study on HIV-positive hemophiliacs in Italy. Italian Group of Congenital Coagulopathies.

BACKGROUND: The effects of zidovudine (ZDV) treatment on progression to AIDS are not completely clear. This study evaluated the effects of ZDV treatment on the progression to AIDS in HIV-positive hemophiliacs. METHODS: A retrospective study was carried out on HIV-infected hemophiliacs: it included 238 individuals, 119 each from the treated and the non-treated groups. For the group receiving ZDV, we included those for whom a CD4+ count was available prior (median = 1 month) to beginning therapy. The cumulative incidence of developing AIDS was estimated by the Kaplan-Meier method. To identify factors independently associated with progression to AIDS, a Cox proportional hazards model was used. RESULTS: The cumulative incidence of developing AIDS at 8 years after HIV seroconversion was 10.4% [standard error (SE) = 2.8%] for the treated group and 17.1% (SE = 3.8%) for the non-treated group. The difference was statistically significant (p = 0.01). By multivariate analysis, ZDV therapy and CD4+ T-cell count > 200/mm3 were the parameters independently associated with a slower progression to AIDS. CONCLUSIONS: Treatment with zidovudine seems to slow the progression to AIDS in HIV-positive hemophiliacs.

Time from diagnosis of acquired immune deficiency syndrome (AIDS) to death among persons with blood-borne AIDS in Italy.

The objective of the study reported here was to analyze survival time and factors associated with more rapid death among persons with acquired immune deficiency syndrome (AIDS) in Italy who acquired human immunodeficiency virus (HIV) infection through the transfusion of blood (n = 115) or blood components (n = 111). Subjects included all persons with AIDS all reported to the Italian AIDS Registry. The Kaplan-Meier method was used to estimate both the median survival time from the date of AIDS diagnosis to the date of death and the median survival time stratified by age at diagnosis, time of diagnosis, and AIDS-indicator disease. The Cox proportional-hazard model was used to assess factors independently associated with death. The prognosis for persons with blood-borne AIDS in Italy remains poor: overall median survival time was estimated to be 9.2 months, with no significant differences between hemophiliacs and transfusion recipients (p = 0.91). The median survival time for subject > 60 years old was 6.0 months, which is a significantly shorter time than that for younger subjects (p < 0.001). Subjects diagnosed prior to 1988 had a median survival time of 8.2 months, which is a significantly shorter time than that for subjects diagnosed after 1987 (p < 0.03). Subjects neurologically affected by AIDS had a median survival time of 4.1 months, which is a significantly shorter time than that for subjects diagnosed with any other disease (p = 0.03). Such factors were independently associated with more rapid death.

Freeze-dried fibular allograft in anterior spinal surgery: cervical and lumbar applications.

Fifty-six patients who underwent anterior fusion utilizing fibular allograft are reviewed. Thirty-two patients underwent multiple-level anterior cervical discectomy and fusion utilizing fibular strut allograft, and 24 underwent anterior lumbar discectomy and fusion using fibular strut allograft. Cervical surgery was performed via the strut technique of Whitecloud and LaRocca and lumbar surgery was performed via a transperitoneal or retroperitoneal approach. Postoperatively, patients were assigned a clinical grade based on symptomatic relief and medication usage. X-rays were visually inspected, and quantitatively digitized for Cobb angle and translation in order to assess the status of arthrodesis. In the cervical group, the rate of clinical success (87.5%) exceeded the arthrodesis rate. By inspection, 65% fused, at a mean time of 23.5 months postoperatively. In the lumbar group, the overall clinical success rate was 68%. This correlated quite strongly with a fusion rate of 58%. Smoking was a negative correlate with arthrodesis. Patients receiving Workers' Compensation were also more likely to have an unsatisfactory clinical outcome. The results of this study highlight the difference between anterior arthrodesis in the cervical and lumbar spine. The biomechanical stability afforded by the fibular strut in the cervical spine appears to outweigh the disadvantages of delayed time to union. The rate of posterior cervical fusion to salvage symptomatic pseudoarthrosis was quite low (9.3%), thus suggesting that additional posterior surgery in this particular group of patients should not be considered for a minimum of two years postoperatively. In the lumbar group, status of arthrodesis correlated closely with clinical outcome. Fusion rate in this group was disappointing, corresponding to other reports in the literature. Based on these data, primary anterior body fusion without allograft in the lumbar spine cannot be recommended, as a viable alternative to conventional autograft.

Splenectomy outcome in a hemophilic patient with HIV-related immune thrombocytopenia.

We report the case of a young hemophilic patient with antibodies against the human immunodeficiency virus (HIV) who was affected by immune thrombocytopenic purpura (ITP). This condition did not respond to pharmacological therapy with steroids and alpha-2b-r-IFN, and the patient was splenectomized. Immune status evaluation was performed before and after surgery and during follow-up with CD4-CD8 monoclonal antibodies and cytofluorimetric analysis in order to explore possible correlations between splenectomy and the cytologic immune regulatory system. Splenectomy resulted in a resolution of ITP with consequent disappearance of the hemorrhagic diathesis related to thrombocytopenia. Moreover, at 30 months from splenectomy the patient is still in remission, his CD4 count is not decreased, and no progression to AIDS has been evidenced. These aspects are analyzed and briefly discussed.

Intranasal DDAVP: biological and clinical evaluation in mild factor VIII deficiency.

We report a study undertaken to test the biological effect of intranasal 1-deamino-8-D-arginine vasopressin (DDAVP) and its efficacy in the treatment of bleedings in patients with mild factor VIII deficiency. The biological study was carried out in 20 patients: an increase of factor VIII:C and von Willebrand factor antigen levels was observed after inhalation of DDAVP at average post/pre inhalation ratios of 2.80 and 1.72, respectively. No relevant alterations of fibrinolysis were noted. In fact, we only observed a simultaneous increase of tissue plasminogen activator and plasminogen activator inhibitor, without modification of D-dimer. In 10 cases intranasal DDAVP has been used in the prevention or in the treatment of bleeding complications: no bleedings were observed.

Essential thrombocythemia: a retrospective study on the clinical course of 100 patients.

We report a study concerning 100 patients affected by essential thrombocythemia: 90 adult (age greater than 20 years) and 10 pediatric subjects. The diagnosis was made by chance (78%), because of hemorrhages (10%), thrombosis (9%), vasomotor symptoms (29%). In the adult group, single-agent chemotherapy was performed with good remission using pipobroman or interferon. Antiaggregant agents were used in all patients at diagnosis. During the clinical course only a few complications occurred.