Comparison of psychotic bipolar disorder, schizoaffective disorder, and schizophrenia: an international, multisite study.

OBJECTIVE: Nosological distinctions among schizoaffective disorder (SA), bipolar I disorder with psychotic features (BDp), and schizophrenia (SZ) remain unresolved. METHOD: We compared 2269 subjects with psychotic features in DSM-IV-TR diagnoses (1435 BDp, 463 SZ, 371 SA) from 8 collaborating international sites, by 12 sociodemographic and clinical measures, all between diagnostic pairs. RESULTS: In bivariate comparisons, SA was consistently intermediate between BDp and SZ for 11/12 features (except onset stressors), and SZ vs. BDp differed in all 12 factors. SA differed from both BDp and SZ in 9/12 factors: SA and BDp were similar in education and suicidal ideation or acts; SA and SZ were similar in education, onset stressors, and substance abuse. Meta-analytic comparisons of diagnostic pairs for 10 categorical factors indicated similar differences of SA from both SZ and BDp. Multivariate modeling indicated significantly independent differences between BDp and SZ (8 factors), SA vs. SZ (5), and BDp vs. SA (3). Measurement variance was similar for all diagnoses. CONCLUSION: SA was consistently intermediate between BDp and SZ. The three diagnostic groups ranked: BDp > SA > SZ related to lesser morbidity or disability. The findings are not consistent with a dyadic Kraepelinian categorization, although the considerable overlap among the three DSM-IV diagnostic groups indicates uncertain boundaries if they represent distinct disorders.

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

BACKGROUND: Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. METHODS: We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). RESULTS: We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). DISCUSSION: Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing.

Redefining the technical and organizational competences of children vaccination clinics in order to improve performance. A practical experience at the ULSS 12 Venetian Public Health and Hygiene Service.

INTRODUCTION: Since Regione Veneto suspended compulsory vaccination for children in 2008, and because of an increasing disaffection of parents to the vaccine practice, the vaccination rates have been slowly but steadily decreasing. The aim of this study was to analyze internal and external factors of immunization reduction and to implement potential solutions of the problem. METHODS: Servizio Igiene e SanitàPubblica of ULSS 12 Venezi-na (SISP - Hygiene and Public Health Service) analyzed and addressed both, the reasons of parents who do not vaccinate their children and the internal problems regarding vaccination clinics management, information to families, procedures and guidelines and, in general, the communication skills of the vaccination staff. RESULTS: A positive trend in vaccination rates was observed, especially in Venice historical centre. Moreover the staff reported a better working atmosphere and benefit from sharing common goals and procedures, even though the workforce was reduced of about 30% in terms of equivalent unit (EU). DISCUSSION: The continuous quality improvement method followed in this experience led to a steady increase in vaccination coverage in all territorial clinics, to a better adhesion of guidelines and standard operating procedures and to a general professional empowerment of SISP staff. The service now offered to the population is better and more efficient, since the workforce has been reduced. Future goals are to improve information about vaccinations among the population.

Is Venice an ideal habitat for Legionella pneumophila?

INTRODUCTION: Legionella bacterium manifests itself in Legionnaire's disease and Pontiac fever, it is mainly found and transmitted by aerosol produced in cooling towers, water distribution plants and medical equipment, and it affects mainly elder persons in poor health. METHODS: The population of Venice Local Health Unit was divided in two areas of study and the incidence of legionellosis in residents of Venice historical centre (Distretto Sanitario 1) and in residents of the mainland and coastal areas (Distretti Sanitari 2, 3, 4) was calculated. The cases were those notified to the Public Health Unit by law, and the population of residents was that of the eligible for health care in the archives of the Local Health Unit. Only cases of legionellosis in residents who had not travelled in the 10 days previous of the onset of disease, and not related to nosocomial clusters were considered. The standardized incidence ratio was then calculated and confidence interval were defined by Poisson distribution. RESULTS: Given the population of the two areas, 59801 in Distretto Sanitario 1 and 237555 in Distretti 2, 3, 4, the raw incidence of disease is respectively 87 per 100000 and 20 per 100000 in time 2002-2010. The standardized incidence ratio for the population of Distretto Sanitario 1 vs the remaining population is 4.3. DISCUSSION: The difference in risk of getting the disease in this two residential areas geographically very close, is probably related to the different buildings' characteristics, old and difficult to maintain in Venice historical centre.

Peripheral tolerance to host minor histocompatibility antigens in radiation bone marrow chimeras abrogates lethal GVHD while preserving GVL effect.

We previously reported that Mls-1a B10.D2 donor preimmunization prevents the development of a lethal graft-versus-host disease (GVHD) directed against host minor histocompatibility antigens (mHAgs) in lethally irradiated (DBA/2 x B10.D2)F1 recipients (LS mice). In the same combination, the graft of T-depleted bone marrow cells also results in no GVHD (TCD BM mice). Both groups of mice exhibit a host specific tolerance. In this paper, we examined whether a graft-versus-leukemia (GVL) effect can still take place without lethal GVHD in LS and TCD BM mice. The i.v. injection of P815 tumor cells into these mice, 2-3 months after the graft, indicates an antitumor activity in LS mice but not in TCD BM mice. When the P815 cells were administered 1 day before irradiation and graft, the leukemic mortality was significantly delayed in mice reconstituted with BM and spleen cells from a preimmunized donor, but not in mice reconstituted with T cell-depleted BM. In LS mice, a subclinical GVHD develops, probably due to CTL alloreactivity against host mHAgs that is observed in vitro. Moreover, cell depletion of the donor inoculum before grafting indicates that the antitumor effect is exclusively mediated by CD8+ T cells. In summary, a beneficial GVL effect, mediated by CD8+ T cells, can be preserved without lethal GVHD.

CD8+ cytotoxic T cell repertoire implicated in grafts-versus-leukemia effect in a murine bone marrow transplantation model.

In our model of murine BMT, the lethal GVHD which develops against DBA/2 host incompatible minor histocompatibility antigens (mHAgs) can be prevented by donor preimmunization before grafting. Recipient mice become long survivors (LS mice) and tolerant to host mHAgs. However, a GVL effect is preserved and mediated by CD8+ CTL able to kill P815 tumor cells in vitro and in vivo. To explain why a GVL exists without GVHD, we compared the CTL activity of LS and B10.D2 donor mice after immunization with DBA/2 spleen cells or with P815 cells. Experimental results indicated that: (1) the level of cytotoxicity for H-2b incompatible cells was similar in LS and B10.D2 mice; (2) CTL recognizing host DBA/2 mHAgs, whose expression is restricted to the spleen or is shared between spleen and P815 cells, were partially unresponsive in LS mice; (3) P815 injection into LS mice predominantly generated CTL specific for antigens restricted to P815 cells, the repertoire of which was not tolerized. Characterization of TCR beta chain showed that the diversity of Vbeta and Jbeta usage by CD8+ T cells activated after P815 injection is considerably restricted in LS mice, compared to B10.D2 donor mice. These results indicated that the GVL effect in LS mice involved mainly T cells specific for tissue-restricted antigens expressed on P815 cells and not on normal DBA/2 spleen cells. In addition, the absence of GVHD may be attributed to the unresponsiveness of CD8+ CTL specific for host mHAgs expressed on DBA/2 spleen cells.

Relative importance of CD4+ and CD8+ T cell repertoires in the development of acute graft-versus-host disease in a murine model of bone marrow transplantation.

T cell repertoire alterations occurring after allogeneic BMT and related emergence of aGVHD has not been directly demonstrated. CD4, CD8 and Vbeta usage of T cells infiltrating spleen, lymph nodes and liver was compared in lethally irradiated F1(DBA/2 x B10.D2) recipients which develop (GVHD mice) or not (long survivor:LS mice) aGVHD across minor histocompatibility antigens (mHAgs) and Mtv-6 and Mtv-7 encoded super-antigens (SAgs) barriers according to experimental conditions. The early expansion in GVHD mice of CD4Vbeta6+ and of CD4Vbeta3+ T cell subsets specific for Mtv-7 and Mtv-6 SAgs, respectively, is abolished in LS protected mice. By contrast, CD8+ T cells infiltrate lymph nodes, the liver but not the spleen of LS as in GVHD mice. Vbeta subset overexpression is frequent in all T cell phenotypes in GVHD but only among CD8+ T cells in LS mice. Predominant Vbeta pattern subpopulation is unique to each mouse. Overexpressed Vbeta subpopulation sequencing clearly indicates that expansion results from a very limited number of clones. Association of a given Vbeta segment with different Jbeta for each mouse suggests that the response is directed towards many different antigens. The data emphasize that Mtv-SAg and mHAgs CD4+ T cells are of crucial importance during GVHD and that there is no relationship between CD8+ T cell repertoires and pathological status.

Newborn blood used as a source of donor cells in a murine model of transplantation across non-MHC antigens.

Cells derived from human cord blood instead of bone marrow were recently used for transplantation. However, several questions concerning the potential of this source of cells to reconstitute the hematopoietic and immunologic system of the recipient and to induce graft-versus-host disease (GVHD) remain unanswered. We used newborn blood (NBB) cells from B10.D2 mice to engraft lethally irradiated (DBA/2 x B10.D2)F1 recipients incompatible for multiple non-H-2 antigens. The median volume of NBB collected from one mouse ranged between 40 and 50 microliters and the number of nucleated cells was approximately 4-5 x 10(5) per sample. We first established that NBB contains around 10-20% of stem cells (SCA-1+) and 30% of CD4+CD8+ Thy-1+ immature T cells. The injection of blood pooled from one to three newborn mice resulted in engraftment of 71%-86% of F1 recipients that survived more than 100 days. Long-term surviving mice exhibited mixed chimerism (approximately 69% of cells of donor origin) 2-4 months after transplantation, and clinical signs of GVHD across minor histocompatibility Ags (mHAgs) were never observed. Additionally, mixed lymphocyte reaction and cytotoxic assay responses of those mice against host antigens were undetectable, while reactivity against unrelated H-2 Ag was normal. The establishment of host-specific tolerance in NBB engrafted mice was confirmed by in vivo transfer experiments. In conclusion, NBB cells reconstituted the lymphohematopoietic system of lethally irradiated mice without inducing GVHD. However, the question of the presence of an active antileukemic effect remains to be answered.

[The quality of hospital discharge data in the Venice general hospital: methods and evaluation in the development of the Diagnosis Related Groups System]. / La qualità dei dati delle schede di dimissione ospedaliera nell'ospedale civile di Venezia: aspetti metodologici e valutativi ai fini dell'utilizzo dei DRG.

In this paper the A.A. illustrate the methodology and development of an evaluation programme of hospital discharge medical records data base quality to implement the DRG system. The work was organized into three phases: the first to analyze the quality base level, the second to sensitize the medical doctors to SDO coding through a Medical Managers Department tutorial action; the third to measure the results of a random sample. The A.A. realized a raise in the compilation level between the two analises, particularly as regards the trascription of surgical procedures and/or diagnostic and therapeutic procedures passed from 39.9% at 64.1%, and a greater correctness in the primary diagnosis coding passed from 69.9% at 83.3% and in the surgical procedures and/or diagnostic and therapeutic procedures (coding) passed from 88.7% at 93.7%.

The appropriateness of human albumin use in the hospital of Padova, Italy.

The authors present the findings of a study in three stages (1989-1991) on the appropriateness of human albumin use at the hospital of Padova, Italy. In the first stage, guidelines for appropriate use were defined and a monitoring system was set up. In the second stage, compliance of the hospital departments with the new guidelines was assessed in a sample of human albumin prescription charts and related medical records. This revealed a reduction in consumption of 25%. Sixty-eight per cent of all albumin was given for indications that are only occasionally appropriate. The information given in the prescription chart agreed with the diagnosis contained in the medical records in 78% of cases. At the end of this stage new regulating mechanisms were introduced. The third stage consisted of a medium-term assessment and produced basically the same results as the previous stage. Crucial steps in the implementation of effective actions in quality improvement processes have been discussed.

Newborn blood can engraft adult mice without inducing graft-versus-host disease across non H-2 antigens.

Cells derived from human cord blood were recently used instead of bone marrow (BM) for transplantation. However, several questions concerning the potential of these cells to reconstitute the hematopoietic and immunologic system of the recipient and to induce a graft-versus-host disease (GVHD) remain unanswered. Here we used newborn blood (NBB) cells from B10.D2 mice to engraft lethally irradiated (DBA/2 x B10.D2)F1 recipients incompatible for multiple non H-2 antigens. Few mature T cells were found in NBB as in adult BM and both contain around 10% to 20% SCA-1+ pluripotent progenitor cells. Yet numerous immature CD4+CD8+ TCR alpha/beta low Thy-1high T cells were present in NBB. In contrast, adult peripheral blood (PB) exhibits a mature T-cell phenotype and contains few progenitor cells. The injection of blood pooled from one to three newborn mice resulted in the engraftment of 71% to 86% of F1 recipients, which survived more than 100 days without clinical signs of GVHD. The injection of BM leads to 100% survival whereas the injection of adult PB resulted in rapid mortality, both without signs of GVHD. In NBB-engrafted F1 surviving mice, T-cell reconstitution preceded B-cell reconstitution, and the degree of donor cell chimerism increased progressively with time. Additionally, 2 to 4 months after transplantation, T cells from these mice were tolerant to host non H-2 antigens but kept reactivity against third-party Ags. Host specific tolerance in NBB-engrafted F1 mice was confirmed by in vivo transfer experiments. In conclusion, NBB cells were able to reconstitute the lymphohematopoietic system of lethally irradiated adult mice without inducing GVHD against incompatible non H-2 antigens. Thus, this experimental model in vivo may be relevant to the human cord blood transplantation.

Utilization of percutaneous transluminal coronary angioplasty for quality assurance in health care from 1983 to 1996.

OBJECTIVES: To examine the distribution of interventional cardiac catheterization laboratories, their case load, the time trends, and the regional variation of percutaneous transluminal cutaneous angioplasty (PTCA) utilization in Italy. METHODS: Analysis of data was provided by the annual reports of the Italian Group of Studies and Interventional Cardiology over the period from 1983 to 1996. RESULTS: The number of PTCA facilities and their use steadily increased, mainly in the North. In 1996 the utilization rate was 34 per 100,000 population, but only 60% of labs performed 200 or more procedures. CONCLUSIONS: Dramatic time trends and regional variations often took place without an epidemiology and technology assessment-based planning process.

Graft-versus-host disease and graft-versus-leukemia effect in mice grafted with peripheral newborn blood.

We previously used peripheral newborn blood (NBB) as a possible in vivo experimental model for cord blood (CB) transplantation and showed that B10.D2 NBB cells successfully reconstituted adult (DBA/2 x B10.D2)F1 mice without causing graft-versus-host disease (GVHD), probably because of their phenotypic and functional immaturity. Here we investigated the influence of T-cell maturation occurring in NBB cells during the early postbirth period on the degree of engraftment, the incidence of GVHD, and the graft-versus-leukemia (GVL) potential. These parameters were compared in recipients grafted with bone marrow (BM) cells. We observed an increased percentage of CD4(+) mature T cells accompanied by the acquisition of proliferative responses to phytohemagglutinin (PHA) and to allogeneic cells of day-5 NBB cells. The capacity of day-2 NBB to engraft was moderately reduced and recipients developing GVHD were occasionally observed after the graft of day-5 NBB cells. No GVL effect was evidenced regardless of the time of postbirth blood collection. However, the GVL effect can be obtained by the delayed infusion of donor mature T cells to recipients grafted with day-0 NBB, without causing GVHD. In contrast, the same protocol applied to mice grafted with BM cells induced GVHD mortality of all recipients. Interleukin (IL)-10 but not IL-2 messenger RNA was expressed in NBB cells as opposed to BM cells. These findings suggest that, in terms of GVHD incidence, delayed infusion of mature T cells as post-transplant tumor immunotherapy would be more effective when applied after CB than after BM transplantation.

Tissue distribution and polymorphism of minor histocompatibility antigens involved in GVHR.

A graft-vs-host reaction (GVHR) develops after major histocompatibility complex (MHC)-compatible bone marrow-transplantation. In the genetic combination studied, B10.D2 donor cells differed from those of (DBA/2 x B10.D2)F1 mice for multiple DBA/2 minor histocompatibility antigens (mHAg) and minor lymphocyte stimulating (Mls) antigens. We investigated the distribution and the cell type expression of mHAg in tissues that were potential GVHR targets, by means of specific T-cell clones derived from mice undergoing reaction. The T-cell clones studied had a CD4+ phenotype and recognized 12 distinct mHAg that were not be product of the Mls-1a gene and that were presented predominantly in association with MHC class II A molecules. Our results indicate that DBA/2 alleles coding for mHAg are frequent in both laboratory and geographically unrelated wild mice. Each mHAg displays an individual pattern of expression on cells present in thymus, skin, gut, and liver. In addition, chimeric mice and established cell lines allowed the identification of cell types expressing mHAg. We found that most mHAg are present on lymphoid and monocyte-macrophage cells, whereas one, distinguished by its absence from lymphoid cells and damaged tissues, is expressed by monocyte-macrophage cells.