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Depression leads to a significant economic and financial burden, which determines the need for implementation of screening programs involving community pharmacists. The aim of this study was to screen patients with chronic conditions for depressive symptoms and to assess their current quality of life at community pharmacies in Sofia Province, Bulgaria. A pilot prospective anonymous survey among patients with chronic diseases was conducted. Questionnaires were used: Patient Health Questionnaire-9 (PHQ-9), EQ-5D-5L and a specially designed questions list. The data were analyzed statistically using MedCalc software version 16.4.1. A total of 119 chronically ill patients were screened for depression by community pharmacists for the period March 2020–August 2020 during and after the first wave of the COVID-19 pandemic. Women (59.7%) and patients over 60 years of age (> 50%) predominated. Most patients had only one disease (47.2%), with the most common diseases being cardiovascular, followed by other endocrine and metabolic diseases. Of the respondents, 64.9% showed depressive symptoms, of which 50.9% were mild and 14% severe. The median pharmacotherapy cost was higher for patients with depression compared to patients who do not show depressive symptoms: BGN 28.50 compared to BGN 14.77. The obtained results suggest that the implementation of an early depression screening service in the community pharmacy settings would provide easy and timely access of patients to adequate mental care. The service would lead to improved quality of pharmaceutical care in Bulgaria and increased range of services that pharmacists offer in community pharmacy practice.

Schizophrenia is a serious mental disorder which requires complex treatment and care. Although proof for effective, cost-effective and affordable treatment is available, health economic research is lacking in many low and middle-income countries. The aim of this study was to evaluate the costs and outcomes for individuals with acute exacerbations of schizophrenia before and after inpatient admission and to evaluate the cost-effectiveness of the current treatment in the clinical practice. We used an ambispective comparative observational health economic study design. The participants were individuals with schizophrenia and their primary caregivers. Costs at baseline and follow-up were evaluated from a healthcare perspective. The primary outcomes were psychopathology, social functioning and quality of life for the patients and burden of informal care for the caregivers. Cost-effectiveness planes and cost-effectiveness acceptability curves were generated to illustrate the cost-effectiveness of treating schizophrenia in the real clinical practice, compared to a do-nothing alternative. The main finding is that treatment of individuals with schizophrenia results in improved outcomes for both patients and caregivers, while it is associated with increased healthcare costs from 135.75 Euro (SD = 193.36) per patient before hospital treatment to 189.00 Euro (SD = 126.98) per patient in the follow-up (95% CI: −112.48; −2.31). After application of sensitivity analysis at a particular level of willingness to pay, the treatment remains cost-effective for all 4 outcomes. In conclusion, the treatment of patients with schizophrenia in Bulgaria is cost-effective at acceptable levels of willingness to pay for a unit of improvement on four different outcomes.

Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (L-CTCL) that arises from malignant clonally derived skin-homing CD4+ T cells. Based on advancements in our understanding of the mechanisms underlying L-CTCL, boosting the suppressed immune response emerges as a promising strategy in SS management. Immune checkpoint inhibitory molecules have already demonstrated efficacy in a wide spectrum of malignancies. Currently, agents targeting the programmed death-1 (PD-1) axis are under evaluation in L-CTCL. Here we investigated the expression of PD-1 and its ligands, PD-L1 and PD-L2 in blood and skin from patients with L-CTCL. We demonstrate that PD-1 expression is markedly increased on tumor T cells compared to non-tumor CD4+ T cells from SS patients and to CD4+ cells from healthy individuals. In contrast, PD-L1 shows decreased expression on tumor T cells, while PD-L2 expression is low without significant differences between these groups. Functional PD-1 blockade in vitro resulted in reduced Th2 phenotype of non-tumor T lymphocytes, but enhanced the proliferation of tumor T cells from SS patients. Our study sheds some light on the PD-1 axis in both peripheral blood and skin compartments in SS patients, which may be relevant for the treatment of L-CTCL with immune checkpoint inhibitor.

Background. The outcome of patients with adenocarcinoma of the esophagogastric junction (AEG) remains poor. The programmed cell-death-protein-1 (PD-1), a co-inhibitory receptor primarily expressed by T-cells, represents a potential new therapeutic target. PD-1, PD-1 ligand 1 (PD-L1), and PD-L2 expression have all been described as prognostic factors in a variety of cancers. Their expression patterns in AEG, however, are poorly understood. We analyzed PD-L1, PD-L2 and PD-1 expression by tumor-infiltrating lymphocytes (TILs) and cancer-cells in tumor-biospecimens in AEG-patients. Methods. 168 patients who underwent esophagectomy because of AEG between 1992–2011 were included in this study. PD-L1, PD-L2 and PD-1 expression were evaluated by immunohistochemistry and correlated with various clinicopathological parameters, disease-free survival (DFS) and long-term overall survival (OS). Results. PD-L1 expression by cancer-cells (cancer-cell-PD-L1+) was found in 43.5% of patients whereas PD-L1 expression by TILs (TILs-PD-L1+) was observed in 69%. PD-L2 expression by cancer-cells and TILs was only found in 3.5% and 1.8%, respectively. Additionally, 77.4% of tumors contained PD-1+-cancer-cells and 81% PD-1+-TILs. Patients with increased expression of PD-1 by cancer-cells and TILs showed significantly reduced OS and DFS, as determined by univariate, but not multivariate analysis. Expression of PD-L1 by cancer-cells was found to be an independent predictor for improved DFS (p = 0.038) and OS (p = 0.042) in multivariate analysis. Conclusions. Cancer cells and TILs displayed PD-L1 expression in around 50% and PD-1 expression in around 80% of tumor-biospecimens obtained from AEG patients. Expression of PD-L1 is an independent predictor of favorable outcome in AEG, whereas PD-1 expression is associated with worse outcome and advanced tumor stage.

Pulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before. 53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study. Tissue samples of resected pulmonary metastases and available corresponding primary tumors were collected and assessed for PD-1, PD-L1 and PD-L2 expression by tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression patterns were correlated with clinical outcome parameters. PD-1 and PD-L1 expression was commonly found in TILs and tumor cells. Expression levels significantly differed between metastases and primary tumors. High PD-1 expression by TILs was associated with impaired overall survival (low vs high expression (mean, 95% CI): 78 mo (60–96) vs 35 mo (25–44); p = 0.011). Additionally, the subgroup of patients, who experienced an upgrading in their TILs/PD1 status between primary and metastasis had a worse survival outcome compared with patients with the same grade or a downgrading (34 mo (26–42) vs 96 mo (72–120); p = 0.004). Thus, PD-1 expression by TILs is a strong prognostic marker in CRC patients with pulmonary spreading treated by PM. Moreover, this study provides a rationale for a therapeutic PD-1 pathway blockade in the treatment of CRC lung metastases. Future, large-scale studies are warranted to validate the findings of this single-center, retrospective analysis.