Developing a cultural competence assessment tool for people in recovery from racial, ethnic and cultural backgrounds: the journey, challenges and lessons learned.

In 1997, Maryland implemented a new managed care mental health system. Consumer satisfaction, evaluation and cultural competency were considered high priorities for the new system. While standardized tools for measuring consumer satisfaction were readily available, no validated, reliable and standardized tool existed to measure the perception of people from minority groups receiving mental health services. The MHA*/MHP* Cultural Competency Advisory Group (CCAG) accepted the challenge of developing a consumer assessment tool for cultural competency. The CCAG, composed of people in recovery, clinicians and administrators used their collective knowledge and experiences to develop a 52-item tool that met standards for validity and reliability. Consultation from a researcher helped to further develop the tool into one possessing tremendous potential for statewide implementation within Maryland's Public Mental Health System. Recognizing the limitations of the study and the need for further research, this instrument is a work in progress. Strategies to improve the instrument are currently underway with the Mental Hygiene Administration's Systems Evaluation Center of the University of Maryland and several national researchers

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

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Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Cinematic transformations of poetic language: Pasolini’s Mamma Roma

Pasolini’s films, especially his early films and writings, are marked by a distinct focus on style and ideology expressed through the use of dialect. In the 1965 essay ‘The cinema of poetry’, “Il cinema di poesia” Pasolini endeavours to provide a theoretical framework for the expressive aesthetic intuition demonstrated by filmmakers, including Pasolini himself. Pasolini discusses the formal character of shot composition and construction in films of the time and labels such stylistic filmmaking ‘poetic’. Utilising the constructs of ‘im-signs’ and ‘free indirect subjectivity’ as derived by Pasolini in his essay, this paper provides a discussion of Pasolini’s own ‘poetic cinema’ as foreshadowed in his second directorial feature Mamma Roma, made in 1962.200

Phenotyping of CYP 4501A2 Activity by Total Overnight Salivary Caffeine Assessment (TOSCA) in Patients on Warfarin Treatment: A Cross-Sectional Study

Warfarin is an oral anticoagulant, commonly used for primary and secondary prevention of venous and arterial thromboembolic events. The drug is characterized by narrow therapeutic index, widespread individual variability in clinical response, and high rates of adverse events, particularly bleeding complications. For these reasons, a close monitoring of the dosage, using the frequent assessment of coagulation status by means of International Normalized Ratio value, is mandatory. Warfarin is metabolized by hepatic cytochrome P-450. High CYP 450 activity may lead to low drug concentration and requires high warfarin doses to reach efficacy; conversely, low CYP 450 activity is responsible for high drug concentration and needs for low doses to avoid potential toxicity risks. The major isoforms of CYP involved in the metabolism of warfarin sodium are CYP1A2 (for the R-warfarin) and CYP2C9 (for the S-warfarin). The probes for testing CYP1A2 are phenacetin and caffeine while for CYP2C9 tolbutamide. Although S-warfarin has major activity, it was decided to exclude its phenotyping for ethical issues, being mandatory to use a drug (tolbutamide). Instead, it was chosen to test the 1A2 isoform, as the activity of the latter isoform could be investigated by using caffeine contained in the caffeinated beverages. Specifically, a single-point concentration of salivary caffeine (total overnight salivary caffeine assessment [TOSCA]) after an overnight period of the caffeinated beverages abstinence was utilized. In the present study, 75 nonsmoker patients regularly receiving warfarin sodium were enrolled. The results have showed a significant association of the warfarin dose with TOSCA values (coefficient = –0.15, standard error = 0.04, 95% confidence interval = –0.24 to –0.06, t = –3.23, P =.002). In conclusion, the phenotyping of CYP1A2 by TOSCA could be useful, if further proven, to help manage patients on warfarin in order to lessen severe adverse events

Alternative macrophage polarisation associated with resistance to anti-PD1 blockade is possibly supported by the splkcing of FKBP51 immunophilin in melanoma patients

Background: FKBP51 immunophilin is abundantly expressed by immune cells. Co-inhibitory immune receptor signalling generates the splicing isoform FKBP51s. Tregs stained by FKBP51s are increased in melanoma patients and their counts are associated with anti-CTLA-4 response. An expansion of FKBP51s+PD-L1+ monocytes was measured in a group of non-responding patients to anti-CTLA-4. The aim of this work was to confirm the predictive value of response of FKBP51s+Tregs in a cohort of patients undergoing anti-PD1 treatment and shed light on a monocyte subset co-expressing PD-L1/FKBP51s. Methods: Co-cultures of organoids and autologous lymphocytes were used to confirm that tumour T-cell interaction can induce FKBP51s. PBMC immunophenotype and flow cytometry served to assess and monitor FKBP51s+Treg and FKBP51s+PD-L1+ monocytes in 22 advanced melanoma patients treated with anti-PD1. Silencing and overexpression of FKBP51s in human macrophages served to address the protein role in the tolerant macrophages' behaviour. Results: FKBP51s+Tregs count was increased in responders and had a prognostic value. Non-responders showed an early increase in FKBP51s+ PD-L1+ monocytes during anti-PD1 treatment. Manipulation of FKBP51s modulated the macrophage-phenotype, with forced protein expression promoting aspects associated with tolerance. Conclusions: FKBP51s may guide in the selection and monitoring of melanoma patient candidates to immune-checkpoint-targeted therapy. Manipulation of FKBP51s may overcome resistance

Identification of a highly suppressive Treg subset associated to immunotherapy response

Background Cancer immunotherapy has shown surprising efficacy in several types of advanced and incurable tumors, particularly, malignant melanoma. There are several immunotherapeutic strategies aimed at enhancing immunological defenses against tumor. Among these, monoclonal antibodies against the so-called “immune checkpoint inhibitors”, that counteract tumor-induced immune-disarming pathways, have shown the best outcomes. Regulatory T lymphocytes or Tregs are a subset of lymphocytes involved in immune-surveillance and maintenance of self-tolerance. Tumor often exploits Tregs to allow tolerance to its own antigens and avoid immune system attack. Tregs are usually increased in melanoma patients. It is noticeable that Tregs is a heterogeneous population with respect to their immunosuppressive capability. Lymphocytes are particularly rich in FKBP51 (FKBP5 gene), an immunophilin better known as the intracellular receptor for FK506 and rapamycin. Melanoma aberrantly expresses this immunophilin, which supports cancer resistance and invasion. Recently, our group has shown that melanoma interaction with immune cells, through PD-L1/PD1, bidirectionally generated the splicing of FKBP5 gene inducing a lower molecular weight form of FKBP51, termed FKBP51s, in both melanoma and lymphocyte. A study performed on PBMC of 64 patients with advanced melanoma (stage III/IV) showed that FKBP51s marks a Treg subset which was correlated, as an independent variable, to anti-CTLA4 (ipilimumab) response. More precisely, a low frequency of Treg FKBP51spos (1.2 and 0.04 and < 0.8%. After a transient increase registered following the first administration, the count decreased to 0.3+0.2% in responder patients. Interestingly, a patient with count = 0.72% developed autoimmune side effects that led to therapy discontinuation. Resolution of side effects was accompanied by an increase in Treg FKBP51s+ value to 9.9%; thenafter, anti-PD1 re-administration produced a successful and objective response. In vitro iTreg generation suggested that FKBP51s was induced in Treg CD25high, Ki67high and p70S6khigh , corresponding to a highly metabolically active profile associated with strong suppressive capability. Conclusion Our data reinforce the hypothesis that melanoma patients that benefit from immune checkpoint targeted therapy are recognizable by an expansion of a Treg subset which plays a central role in de-activation of stimulatory co-signalling pathways, in support of tumor immune evasion. Such a Treg subset is marked by FKBP51s, a splicing protein isoform generated by triggering of surface antigens (PD-L1, PD1) that are abundantly expressed on highly suppressive Tregs