Barriers to the implementation of advanced clinical pharmacy services at Portuguese hospitals

Background In some countries, such as Portugal, clinical pharmacy services in the hospital setting may be implemented to a lower extent than desirable. Several studies have analysed the perceived barriers to pharmacy service implementation in community pharmacy. Objective To identify the barriers towards the implementation of advanced clinical pharmacy services at a hospital level in Portugal, using medication follow-up as an example. Setting Hospital pharmacies in Portugal. Methods A qualitative study based on 20 face-to-face semi-structured interviews of strategists and hospital pharmacists. The interview guide was based on two theoretical frameworks, the Borum’s theory of organisational change and the Social Network Theory, and then adapted for the Portuguese reality and hospital environments. A constant comparison process with previously analysed interviews, using an inductive approach, was carried out to allow themes to emerge. Themes were organised following the Leavitt’s Organizational Model: functions and objectives; hospital pharmacist; structure of pharmacy services; environment; technology; and medication follow-up based on the study topic. Main outcome measure Barriers towards practice change. Results Medication follow-up appeared not to be a well-known service in Portuguese hospital pharmacies. The major barriers at the pharmacist level were their mind-set, resistance to change, and lack of readiness. Lack of time, excessive bureaucratic and administrative workload, reduced workforce, and lack of support from the head of the service and other colleagues were identified as structural barriers. Lack of access to patients’ clinical records and cumbersome procedures to implement medication follow-up were recognised as technological barriers. Poor communication with other healthcare professionals, and lack of support from professional associations were the major environmental barriers. Conclusion Few of the barriers identified by Portuguese hospital pharmacists were consistent with previous reports from community pharmacy. The mind-set of pharmacists and predetermined attitudes are recognised as barriers that can give rise to new perceived barriers.     

Conventional type 1 dendritic cells induce TH1, TH1-like follicular helper T cells and regulatory T cells after antigen boost via DEC205 receptor

Conventional dendritic cells (cDCs) are specialized in antigen presentation. In the mouse spleen, cDCs are classified in cDC1s and cDC2s, and express DEC205 and DCIR2 endocytic receptors, respectively. Monoclonal antibodies (mAbs) αDEC205 (αDEC) and αDCIR2 have been fused to different antigens to deliver them to cDC1s or cDC2s. We immunized mice with αDEC and αDCIR2 fused to an antigen using Poly(I:C) as adjuvant. The initial immune response was analyzed from days 3 to 6 after the immunization. We also studied the influence of a booster dose. Our results showed that antigen targeting to cDC1s promoted a pro-inflammatory T_H1 cell response. Antigen targeting to cDC2s induced T_FH cells, GCs, and plasma cell differentiation. After boost, antigen targeting to cDC1s improved the T_H1 cell response and induced T_H1-like T_FH cells that led to an increase in specific antibody titers and IgG class switch. Additionally, a population of regulatory T cells was also observed. Antigen targeting to cDC2s did not improve the specific antibody response after boost. Our results add new information on the immune response induced after the administration of a booster dose with αDEC and αDCIR2 fusion mAbs. These results may be useful for vaccine design using recombinant mAbs.     

T-cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

Multifunctional interleukin 10 (IL10)⁺Th1 cells have been implicated in favorable evolution of many infectious diseases, promoting an efficacious immune response while limiting immunopathology. Here, we investigated the presence of multifunctional CD4⁺ and CD8⁺ T-cells that expressed interferon gamma (IFNγ), IL10 and tumor necrosis factor (TNF), or its combinations during dengue infection. Peripheral blood mononuclear cells (PBMCs) from outpatients with dengue (mild dengue forms) and hospitalized patients (or patients with dengue with warning signs and severe dengue) were cultured in the presence of envelope (ENV) or NS3 peptide libraries of DENV during critical (hospitalization period) and convalescence phases. The production of IFNγ, IL10 and TNF by CD4⁺ and CD8⁺ T-cells was assessed by flow cytometry. Our data show that patients with mild dengue, when compared with patients with dengue with warning signs and severe dengue, presented higher frequencies of multifunctional T-cells like NS3-specific IFNγ/IL10-producing CD4⁺ T-cells in critical phase and NS3- and ENV-specific CD8⁺ T-cells producing IFNγ/IL10. In addition, NS3-specific CD8⁺ T-cells producing high levels of IFNγ/TNF and IFNγ/TNF/IL10 were also observed in the mild dengue group. We observed that multifunctional T-cells produced higher levels of cytokines as measured by intracellular content when compared with single producer T-cells. Importantly, multifunctional CD4⁺ and CD8⁺ T-cells producing IFNγ, TNF and IL10 simultaneously displayed positive correlation with platelet levels, suggesting a protective role of this population. The presence of IL10⁺Th1 and IL10⁺Tc1 multifunctional cells was associated with mild dengue presentation, suggesting that these cells play a role in clinical evolution of dengue infection.     

Further delineation of putative ACTB loss‐of‐function variants: A 4‐patient series

ACTB encodes β‐cytoplasmic actin, an essential component of the cytoskeleton. Based on chromosome 7p22.1 deletions that include the ACTB locus and on rare truncating ACTB variants, a phenotype resulting from ACTB haploinsufficiency was recently proposed. We report putative ACTB loss‐of‐function variants in four patients. To the best of our knowledge, we report the first 7p22.1 microdeletion confined to ACTB and the second ACTB frameshifting mutation that predicts mRNA decay. A de‐novo ACTB p.(Gly302Ala) mutation affects β‐cytoplasmic actin distribution. All four patients share a facial gestalt that is distinct from that of individuals with dominant‐negative ACTB variants in Baraitser‐Winter cerebrofrontofacial syndrome. Two of our patients had strikingly thin and sparse scalp hair. One patient had sagittal craniosynostosis and hypospadias. All three affected male children have attention deficits and mild global developmental delay. Mild intellectual disability was present in only one patient. Heterozygous ACTB deletion can allow for normal psychomotor function.     

Ambivalence in Psychotherapy Questionnaire: Development and validation studies

Research emphasizes that individuals' engagement with change process is a significant predictor of therapeutic outcomes. Ambivalence is a natural phenomenon in change processes, but when individuals cannot overcome it, their problems may intensify. Ambivalence towards change, a client variable characterized by an intrapersonal conflict between two positions of the self, one in favour of change and another one in favour of the status quo, is shown to play a determinant role in psychotherapy. Despite its importance, few empirical studies have examined this process, and the considerable methodological differences among existing studies make it difficult to generalize results. Therefore, instruments measuring ambivalence in an effective way can help broaden the understanding of the process. First, we performed a content analysis of ambivalence events identified in psychotherapy sessions from previous studies using an observational coding system. The factor structure, reliability and validity of the measure were tested using 91 and confirmed with 223 psychotherapy clients at any time during the therapeutic process. A two‐factor structure was found, suggesting two components of Ambivalence—Demoralization and Wavering. The results indicated that the Ambivalence in Psychotherapy Questionnaire exhibits good psychometric properties, including good convergent and divergent validity. The implications are discussed.     

Cytologic features of vaping‐induced lung injury: A case report

Vaping‐induced lung injury is a recently recognized phenomenon owing to the rising popularity of e‐cigarette use. A cluster of cases of varying severity, including six deaths, was recently reported in the United States by the Centers for Disease Control. The objective of this report is to highlight the cytologic features suggestive of vaping‐induced lung injury. A 20‐year‐old previously healthy man presented with a 7‐day history of progressively worsening respiratory symptoms including dyspnea on exertion, cough, and fever, with no improvement after initiating a course of antibiotics. No relevant travel or occupational history was reported, but patient endorsed daily use of e‐cigarette with a fluid containing both tetrahydrocannabinol and nicotine. Radiographic studies demonstrated scattered areas of interlobular septal thickening and diffuse ground‐glass opacities in both lungs. Laboratory tests for HIV and influenza were negative. Bronchoscopy and bronchoalveolar lavage were performed, with cytologic study showing clusters of benign bronchial cells and an increase in lipid‐laden macrophages by Oil Red O stain. Patient was placed on steroid and steadily improved for the next 2 days. He was discharged on a steroid taper and follow‐up with respiratory clinic. Case reports and series have shown a variety of lung injury patterns in previously healthy patients who are frequent users of e‐cigarettes and among them features suggestive of lipoid pneumonia with increased lipid‐laden macrophages. The clinical utility of this finding is still unclear.