Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation

Background The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. Methods Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. Results In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade >= 3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). Conclusions We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure

Are antidepressants equally effective in the long-term treatment of major depressive disorder?

OBJECTIVE: Few studies have compared simultaneously different antidepressants in long-term treatment of major depressive disorder (MDD). Long-term prevention of recurrences should be the main goal of MDD treatment. The purpose of this study was to compare antidepressants of different pharmacological classes in terms of retention in treatment (no discontinuation for recurrences, hospitalizations, side effects). METHODS:One hundred and fifty outpatients with an MDD diagnosis, treated with antidepressants in mono-therapy, were included. Follow-up period was set at 24\u2009months, and information have been obtained from charts, interviews with patients and their relatives, and from the Lombardy regional register. A survival analysis (Kaplan-Meier) was performed, considering recurrences, hospitalizations, or discontinuation due to side effects as 'death' events. RESULTS: In our sample, 48.7% of the patients presented a recurrence within the first 2\u2009years of treatment. Bupropion appears less effective in long-term treatment of MDD than the other compared antidepressants, with exception of fluoxetine (p\u2009=\u20090.09), amitriptyline (p\u2009=\u20090.13), fluvoxamine (p\u2009=\u20090.83), venlafaxine (p\u2009=\u20090.5), and trazodone (p\u2009=\u20090.58). Fluvoxamine appears to be less effective than citalopram (p\u2009=\u20090.036), paroxetine (p\u2009=\u20090.037), clomipramine (p\u2009=\u20090.05), sertraline (p\u2009=\u20090.011), and duloxetine (p\u2009=\u20090.024). CONCLUSIONS: Bupropion and fluvoxamine appear less effective in long-term treatment of MDD. These results should be confirmed by randomized placebo-controlled prospective studies with larger samples

Efeito da sucção e do nível de tensão no comportamento de um solo tropical naturalmente cimentado

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Efeito da sucção e do nível de tensão no comportamento de um solo tropical naturalmente cimentado

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Biological aspects and candidate biomarkers for psychotic bipolar disorder: a systematic review

AIM:We carried out a systematic review of the available literature about potential biomarkers of psychotic bipolar disorder (BD-P), a specific subset presenting worse outcome and greater risk of relapse than non-psychotic bipolar disorder (BD-NP). METHODS:We searched the main psychiatric databases (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles with the main topic of BD-P compared to schizophrenia/BD-NP/healthy controls (HC) written in English from 1994 to 2015 were included. RESULTS: BD-P patients presented higher kynurenic acid levels in the cerebrospinal fluid, elevated anti- S accharomyces cerevisiae antibodies levels, and lower serum levels of dehydroepiandrosterone sulfate and progesterone than BD-NP/HC. Event-related potentials abnormalities have been identified in BD-P with respect to BD-NP. BD-P patients also presented bigger ventricles but similar hippocampal volumes compared to BD-NP/HC. Although the results are contrasting, some cognitive deficits seemed to be related to the psychotic dimension of bipolar affective disorder, such as impairment in verbal/logical memory, working memory, verbal and semantic fluency and executive functioning. Finally, polymorphisms of genes, such as NRG1, 5HTTLPR (s), COMT, DAOA and some chromosome regions (16p12 and 13q), were positively associated with BD-P. CONCLUSION:Data about the identification of specific biomarkers for BD-P are promising, but most of them have not yet been replicated. They could lead the clinicians to an early diagnosis and proper treatment, thus ameliorating outcome of BD-P and reducing the biological changes associated with a long duration of illness. Further studies with bigger samples are needed to detect more specific biological markers of the psychotic dimension of bipolar affective disorder

Estudo preliminar de um escorregamento de solo e rocha na localidade de Malhada, Santa Cruz do Sul

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Estudo preliminar de um escorregamento de solo e rocha na localidade de Malhada, Santa Cruz do Sul

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An evaluation of the quality of obstetric morbidity coding using an objective assessment tool, the Performance Indicators for Coding Quality (PICQ)

The Performance Indicators for Coding Quality (PICQ) is a data quality assessment tool developed by Australia\u27s National Centre for Classification in Health (NCCH). PICQ consists of a number of indicators covering all ICD-10-AM disease chapters, some procedure chapters from the Australian Classification of Health Intervention (ACHI) and some Australian Coding Standards (ACS). The indicators can be used to assess the coding quality of hospital morbidity data by monitoring compliance of coding conventions and ACS; this enables the identification of particular records that may be incorrectly coded, thus providing a measure of data quality. There are 31 obstetric indicators available for the ICD-10-AM Fourth Edition. Twenty of these 31 indicators were classified as Fatal, nine as Warning and two Relative. These indicators were used to examine coding quality of obstetric records in the 2004-2005 financial year Australian national hospital morbidity dataset. Records with obstetric disease or procedure codes listed anywhere in the code string were extracted and exported from the SPSS source file. Data were then imported into a Microsoft Access database table as per PICQ instructions, and run against all Fatal and Warning and Relative (N=31) obstetric PICQ 2006 Fourth Edition Indicators v.5 for the ICD-10- AM Fourth Edition. There were 689,905 gynaecological and obstetric records in the 2004-2005 financial year, of which 1.14% were found to have triggered Fatal degree errors, 3.78% Warning degree errors and 8.35% Relative degree errors. The types of errors include completeness, redundancy, specificity and sequencing problems. It was found that PICQ is a useful initial screening tool for the assessment of ICD-10-AM/ACHI coding quality. The overall quality of codes assigned to obstetric records in the 2004- 2005 Australian national morbidity dataset is of fair quality

Misdiagnosis, duration of untreated illness (DUI) and outcome in bipolar patients with psychotic symptoms : a naturalistic study

Background: A number of data show the negative role of duration of untreated illness (DUI) on outcome in mood disorders, but no investigation has been carried out about the impact of this variable in bipolar disorder (BD) with psychotic symptoms. Clinical experience shows that many bipolar patients with psychotic symptoms receive other diagnoses and often are chronically treated with first generation antipsychotics, with the effect to reduce duration of untreated psychosis/untreated episode with psychotic symptoms (DUP), but not DUI. Purpose of the study was to define the rate of misdiagnosis and the impact of DUP/DUI on outcome of bipolar patients with psychotic symptoms. Method: Clinical information (DUP. DUI, first received diagnosis) about bipolar outpatients with psychotic symptoms (N=240) were extrapolated through a retrospective review of the clinical charts, Lombardy database and, if necessary, through clinical interviews with patients and their relatives. Outcome measures included psychiatric and substance abuse comorbidity, occupational status, Global Assessment of Functioning (GAF), number of hospitalizations and of suicidal attempts, number of depressive/manic recurrences. Patients were divided in two groups according to the DUP (1 year) and DUl (8 years) median, and the groups were compared through analyses of variance (ANOVAs) for continuous variables or chi(2) tests for dichotomous ones. Multivariate analysis of variance (MANOVA) with duration of illness as covariate was then performed to eliminate the effect of this variable. Finally, binary logistic regressions were performed considering age at onset, DUI, DUP as independent variables and outcome variables as dependent ones (presence of hospitalizations/suicidal attempts, GAF scores < 50, occupational status). Results: Most of patients (61.5%) received a first diagnosis different horn BD with the most frequent DSM-diagnosis being delusional disorder (17.9%). Patients with longer DUP were not different in outcome measures with respect to patients with shorter DUP. Patients with a DUI >8 years presented higher number of hospitalizations (F=6.04, p=0.015), higher number of manic recurrences (F=5.25, p=0.023), higher number of depressive recurrences (F=7.13, p=0.008) and lower GAF scores (F=17.74, p < 0.001). Statistical significance persisted for number of hospitalizations (p < 0.001) and GAF scores (p=0.003) after MANOVA. Finally binary logistic regression showed that a longer DUl was predictive of GAF scores < 50 (F=1774, p < 0.001). Discussion: More than half of bipolar patients with psychotic symptoms receive a different diagnosis at first contact with psychiatric services. DUI (but not DUP) is a predictor of outcome in bipolar patients with psychotic symptoms. This indicates that an early diagnosis and proper treatment with a mood stabilizer (or an atypical antipsychotic with mood stabilizing effects) may improve long-term outcome of these patients. In the light of the naturalistic design of the present paper, these results have to be considered as preliminary and have to be confirmed by prospective controlled studies

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