Assessing the quality of the care offer for people with personality disorders in Italy: the QUADIM project. A multicentre research based on the database of use of Mental Health services

Background: Italy can be viewed as a laboratory to assess the quality of mental healthcare delivered in a community-oriented system, especially for severe mental disorders, such as personality disorders. Although initiatives based on clinical indicators for assessing the quality of mental healthcare have been developed by transnational-organisations, there is still no widespread practice of measuring the quality of care pathways delivered to patients with severe mental disorders in a community-oriented system, especially using administrative healthcare databases. The aim of the study is to evaluate the quality of care delivered to patients with personality disorders taken-in-care by mental health services of four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily). Methods: A set of thirty-three clinical indicators, concerning accessibility, appropriateness, continuity, and safety of care, was implemented using regional healthcare utilization databases, containing data on mental health treatments and diagnosis, hospital admissions, outpatient interventions and exams and drug prescriptions. RESULTS: 31,688 prevalent patients with personality disorders treated in 2015 were identified, of whom 2,331 newly taken-in-care. One-in-10 patients received a standardized assessment, the treatment discontinuity affected half of the cases. 12.7% of prevalent patients received at least one hospitalization, 10.6% in the newly taken-in-care cohort. 6-out-of-10 patients had contact with community-services within 14 days from hospital discharge. Access to psychotherapy and psychoeducational treatments was low and delivered with a low intensity. The median of psychosocial interventions per person-year was 19.1 and 9.4, respectively, in prevalent and newly taken-in-care cases. Nearly 50% of patients received pharmacological treatments. Conclusions: Healthcare utilization databases were used to systematically evaluate and assess service delivery across regional mental health systems; suggesting that in Italy the public mental health services provide to individuals with personality disorders suboptimal treatment paths

Role of Hog1 and Yaf9 in the transcriptional response of Saccharomyces cerevisiae to cesium chloride

We analyzed the global transcriptional response of Saccharomyces cerevisiae cells exposed to different concentrations of CsCl in the growth medium and at different times after addition. Early responsive genes were mainly involved in cell wall structure and biosynthesis. About half of the induced genes were previously shown to respond to other alkali metal cations in a Hog1-dependent fashion. Western blot analysis confirmed that cesium concentrations as low as 100 mM activate Hog1 phosphorylation. Another important fraction of the cesium-modulated genes requires Yaf9p for full responsiveness as shown by the transcriptome of a yaf9-deleted strain in the presence of cesium. We showed that a cell wall-restructuring process promptly occurs in response to cesium addition, which is dependent on the presence of both Hog1 and Yaf9 proteins. Moreover, the sensitivity to low concentration of cesium of the yaf9-deleted strain is not observed in a strain carrying the hog1/yaf9 double deletion. We conclude that the observed early transcriptional modulation of cell wall genes has a crucial role in S. cerevisiae adaptation to cesium

A genetic modifier of venous thrombosis in zebrafish reveals a functional role for fibrinogen AαE in early hemostasis

Plasma fibrinogen molecules comprise 2 copies of Aα, Bβ, and γ chains folded into a hexameric protein. A minor fibrinogen isoform with an extended Aα chain (AαE) is more abundant in newborn human blood than in adults. Larval zebrafish produce predominantly AαE-containing fibrinogen, but its functional significance is unclear. In 3-day-old zebrafish, when hemostasis is reliant on fibrinogen and erythrocyte-rich clotting but is largely thrombocyte-independent, we measured the time to occlusion (TTO) in a laser-induced venous thrombosis assay in 3 zebrafish strains (AB, TU, and AB × TL hybrids). AB larvae showed delayed TTO compared with the TU and AB × TL strains. Mating AB with TU or TL produced larvae with a TU-like TTO. In contrast to TU, AB larvae failed to produce fibrinogen AαE, due to a mutation in the AαE-specific coding region of fibrinogen α-chain gene (fga). We investigated whether the lack of AαE explained the delayed AB TTO. Transgenic expression of AαE, but not Aα, shortened the AB TTO to that of TU. AαE rescued venous occlusion in fibrinogen mutants or larvae with morpholino-targeted fibrinogen α-chain messenger RNA, but Aα was less effective. In 5-day-old larvae, circulating thrombocytes contribute to hemostasis, as visualized in Tg(itga2b:EGFP) transgenics. Laser-induced venous thrombocyte adhesion and aggregation is reduced in fibrinogen mutants, but transgenic expression of Aα or AαE restored similar thrombocyte accumulation at the injury site. Our data demonstrate a genetic modifier of venous thrombosis and a role for fibrinogen AαE in early developmental blood coagulation, and suggest a link between differentially expressed fibrinogen isoforms and the cell types available for clotting

The quality of mental health care for people with bipolar disorders in the Italian mental health system: the QUADIM project

BackgroundThe assessment of the quality of care pathways delivered to people with severe mental disorders in a community-based system remains uncommon, especially using healthcare utilization databases. The aim of the study was to evaluate the quality of care provided to people with bipolar disorders taken-in-care by mental health services of four Italian areas (Lombardy, Emilia-Romagna, Lazio, province of Palermo).MethodsThirty-six quality indicators were implemented to assess quality of mental health care for patients with bipolar disorders, according to three dimensions (accessibility and appropriateness, continuity, and safety). Data were retrieved from healthcare utilization (HCU) databases, which contain data on mental health treatments, hospital admissions, outpatient interventions, laboratory tests and drug prescriptions.Results29,242 prevalent and 752 incident cases taken-in-care by regional mental health services with a diagnosis of bipolar disorder in 2015 were identified. Age-standardized treated prevalence rate was 16.2 (per 10,000 adult residents) and treated incidence rate 1.3. In the year of evaluation, 97% of prevalent cases had >= 1 outpatient/day-care contacts and 88% had >= 1 psychiatric visits. The median of outpatient/day-care contacts was 9.3 interventions per-year. Psychoeducation was provided to 3.5% of patients and psychotherapy to 11.5%, with low intensity. 63% prevalent cases were treated with antipsychotics, 71.5% with mood stabilizers, 46.6% with antidepressants. Appropriate laboratory tests were conducted in less than one-third of prevalent patients with a prescription of antipsychotics; three quarters of those with a prescription of lithium. Lower proportions were observed for incident patients. In prevalent patients, the Standardized Mortality Ratio was 1.35 (95% CI: 1.26-1.44): 1.18 (1.07-1.29) in females, 1.60 (1.45-1.77) in males. Heterogeneity across areas was considerable in both cohorts.ConclusionsWe found a meaningful treatment gap in bipolar disorders in Italian mental health services, suggesting that the fact they are entirely community-based does not assure sufficient coverage by itself. Continuity of contacts was sufficient, but intensity of care was low, suggesting the risk of suboptimal treatment and low effectiveness. Care pathways were monitored and evaluated using administrative healthcare databases, adding evidence that such data may contribute to assess the quality of clinical pathways in mental health

Assessment and Monitoring of the Quality of Clinical Pathways in Patients with Depressive Disorders: Results from a Multiregional Italian Investigation on Mental Health Care Quality (the QUADIM Project)

Ensuring adequate quality of care to patients with severe mental disorders remains a challenge. The implementation of clinical indicators aimed at assessing the quality of health care pathways delivered is crucial for the improvement of mental health services (MHS). This study aims to evaluate the quality of care delivered to patients who are taken-into-care with depressive disorders by MHS. Thirty-four clinical indicators concerning accessibility, appropriateness, continuity, and safety were estimated using health care utilization databases from four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily). A total of 78,924 prevalent patients treated for depressive disorders in 2015 were identified, of whom 15,234 were newly engaged by MHS. During the year of follow-up, access to psychotherapeutic interventions was low, while the intensity was adequate; 5.1% of prevalent patients received at least one hospitalization in a psychiatric ward (GHPW), and 3.3% in the cohort of newly engaged in services. Five-out-of-10 patients had contact with community services within 14 days after GHPW discharge, but less than half of patients were persistent to antidepressant drug therapy. Furthermore, prevalent patients showed an excess of mortality compared to the general population (SMR = 1.35; IC 95%: 1.26-1.44). In conclusion, the quality of health care is not delivered in accordance with evidence-based mental health standards. Evaluation of health interventions are fundamental strategies for improving the quality and equity of health care

Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations12

The Raf/MEK/ERK pathway is an important mediator of tumor cell proliferation and angiogenesis. Here, we investigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1) and apoptosis (Bcl-2 and survivin) regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma

Additional file 1 of Assessing the quality of the care offer for people with personality disorders in Italy: the QUADIM project. A multicentre research based on the database of use of Mental Health services

Supplementary Material