Challenges to access and provision of palliative care for people who are homeless : a systematic review of qualitative research

Background: People who are homeless or vulnerably housed are a marginalized group who often experience high rates of morbidity and die young as a result of complex problems. Access to health care and support can be challenging, with access to palliative care even more so. This review presents a synthesis of published qualitative research exploring from the perspective of homeless people and those working to support them, current challenges to palliative care access and provision, in addition to suggestions for what may improve palliative care for this population. Methods: Systematic review of qualitative research analysed using thematic synthesis. PsycINFO, Medline, Sociological Abstracts, Social Services Abstracts, Science citations index and CINAHL were searched up to September 2016. Thematic synthesis involved a three-step inductive process to develop a deeper understanding of the challenges to and suggestions for the access and provision of palliative care for homeless people. Results: Thirteen qualitative articles, reporting nine studies were identified. The challenges to access and provision to palliative care were drawn from the data covering three broad areas, namely “the chaotic lifestyles sometimes associated with being homeless”, “the delivery of palliative care within a hostel for homeless people” and provision within “mainstream health care systems”. Obstacles were related to homeless persons competing day-to-day priorities, their experience of stigma in mainstream settings, the high burden on hostel staff in supporting residents at the end of life and inflexibility in mainstream health care systems. Suggestions for improving access to palliative care include building trust between homeless persons and health professionals, increasing collaboration between and flexibility within services, and providing more training and support for all professionals. Conclusions: The provision of palliative care can be complicated for all populations, however delivering palliative care for people who are homeless is influenced by a potentially greater and more varied range of factors, on both individual and systemic levels, than providing palliative care for the housed population. Careful consideration and potentially great changes will be needed within health care systems to ensure homeless populations have equitable access to palliative care

Rare missense variants in Tropomyosin-4 (TPM4) are associated with platelet dysfunction, cytoskeletal defects, and excessive bleeding

Background: A significant challenge is faced for the genetic diagnosis of inherited platelet disorders in which candidate genetic variants can be found in more than 100 bleeding, thrombotic, and platelet disorder genes, especially within families in which there are both normal and low platelet counts. Genetic variants of unknown clinical significance (VUS) are found in a significant proportion of such patients in which functional studies are required to prove pathogenicity. Objective: To identify the genetic cause in patients with a suspected platelet disorder and subsequently perform a detailed functional analysis of the candidate genetic variants found. Methods: Genetic and functional studies were undertaken in three patients in two unrelated families with a suspected platelet disorder and excessive bleeding. A targeted gene panel of previously known bleeding and platelet genes was used to identify plausible genetic variants. Deep platelet phenotyping was performed using platelet spreading analysis, transmission electron microscopy, immunofluorescence, and platelet function testing using lumiaggregometry and flow cytometry. Results: We report rare conserved missense variants (p.R182C and p.A183V) in TPM4 encoding tromomyosin-4 in 3 patients. Deep platelet phenotyping studies revealed similar platelet function defects across the 3 patients including reduced platelet secretion, and aggregation and spreading defects suggesting that TPM4 missense variants impact platelet function and show a disordered pattern of tropomyosin staining. Conclusions: Genetic and functional TPM4 defects are reported making TPM4 a diagnostic grade tier 1 gene and highlights the importance of including TPM4 in diagnostic genetic screening for patients with significant bleeding and undiagnosed platelet disorders, particularly for those with a normal platelet count

Patient empowerment in long-term conditions: development and preliminary testing of a new measure

BACKGROUND: Patient empowerment is viewed by policy makers and health care practitioners as a mechanism to help patients with long-term conditions better manage their health and achieve better outcomes. However, assessing the role of empowerment is dependent on effective measures of empowerment. Although many measures of empowerment exist, no measure has been developed specifically for patients with long-term conditions in the primary care setting. This study presents preliminary data on the development and validation of such a measure. METHODS: We conducted two empirical studies. Study one was an interview study to understand empowerment from the perspective of patients living with long-term conditions. Qualitative analysis identified dimensions of empowerment, and the qualitative data were used to generate items relating to these dimensions. Study two was a cross-sectional postal study involving patients with different types of long-term conditions recruited from general practices. The survey was conducted to test and validate our new measure of empowerment. Factor analysis and regression were performed to test scale structure, internal consistency and construct validity. RESULTS: Sixteen predominately elderly patients with different types of long-term conditions described empowerment in terms of 5 dimensions (identity, knowledge and understanding, personal control, personal decision-making, and enabling other patients). One hundred and ninety seven survey responses were received from mainly older white females, with relatively low levels of formal education, with the majority retired from paid work. Almost half of the sample reported cardiovascular, joint or diabetes long-term conditions. Factor analysis identified a three factor solution (positive attitude and sense of control, knowledge and confidence in decision making and enabling others), although the structure lacked clarity. A total empowerment score across all items showed acceptable levels of internal consistency and relationships with other measures were generally supportive of its construct validity. CONCLUSION: Initial analyses suggest that the new empowerment measure meets basic psychometric criteria. Reasons concerning the failure to confirm the hypothesized factor structure are discussed alongside further developments of the scale

Prognostic Factors for Post-Transplant Outcomes in Patients with Myelodysplastic Syndromes (MDS)

Abstract Abstract 2015 Allogeneic hematopoietic stem cell transplantation (AlloSCT) remains the only curative option for MDS. Several retrospective studies evaluated the impact of various prognostic factors (i.e. cytogenetic risk group, WHO classification, ferritin level etc.) on post-transplant outcomes of pts with MDS, however comprehensive analyses including a cytogenetic abnormalities detected by SNP array (SNP-A) karyotyping method have not been performed. We have analyzed prognostic factors of post-AlloSCT outcomes among 74 pts with MDS (2000–2010) including the predictive value of SNP-A abnormalities. Cox proportional hazards analysis was used to identify univariable prognostic factors for acute GVHD (aGVHD), chronic GVHD (cGVHD), disease relapse, relapse free (RFS) and overall survival (OS). Multivariable prognostic factors were identified by stepwise Cox proportional hazards analysis. The median time from MDS diagnosis to transplant for all pts was 6 mos (range, 0.2– 141 mos). The median age at transplant was 51 yrs; 32% of the pts had a hematopoietic cell transplant co-morbidity index (HCT-CI) score ≥ 3; 69% had ≥1 prior chemotherapies; and only 30% were in remission prior to their transplant. 27 pts (37%) had RAEB-2, 11 (15%) had RAEB-1, and 9 (12%) had treatment-related MDS. 42 pts (58%) belonged to an intermediate-2 or higher IPSS risk category. 23 pts (31%) had adverse karyotype (complex or monosomy 7) detected by metaphase cytogenetics (MC). SNP abnormalities were identified in 58% of patients; 79% of all patients with SNP abnormalities had lesions not previously detected by traditional cytogenetic techniques. Median pre-transplant ferritin level was 1127 (range, 9–5201). 73% of the pts received myeloablative conditioning. In 61% of cases stem cells were harvested from the bone marrow. Matched related donors accounted for half of the cases. Twelve pts (16%) died within 100 days of transplant and 39 pts (53%) within the median follow up of 36 mos (range, 5–114). MDS relapse occurred in 22 pts (30%). The rates of grade II-IV aGVHD and extensive cGVHD were 49% and 24% respectively. Disease relapse was the most common cause of death (31%) followed by aGVHD (18%) and cGVHD (13%). In univariate analysis, aGVHD was associated with myeloablative (p<0.01) and non-TBI (p=0.01) containing regimens. Disease relapse was associated with increased number of prior chemotherapy regimens (p=0.04), whereas the OS was associated with higher level of pre-transplant ferritin level (p=0.01). In multivariable analysis, only high pre-transplant ferritin level predicted for worse OS (p=0.01) and only myeloablative conditioning predicted aGVHD (p=0.01). When the group with complex cytoegenetics or ≥3 SNP abnormalities was compared with the rest of the patients, relapse occurred more frequently and RFS and OS was reduced, however the high risk group was too small to detect a statistically significant difference. Our data demonstrate elevated pre-transplant ferritin level to be the only independent predictor for inferior OS in pts with MDS undergoing AlloSCT. The prognostic role of SNP-A abnormalities in addition to chromosomal lesions detected by MC in post-transplant setting needs to be validated in a larger group of MDS pts. Disclosures: Sekeres: Celgene: Consultancy, Honoraria, Speakers Bureau

The Impact of Molecular Lesions in Post-Transplant Acute Myeloid Leukemia (AML) in Correlation with Cytogenetic Abnormalities

Abstract Abstract 4137 Relapse remains the most common cause of treatment failure in allogeneic hematopoietic stem cell transplantation (AlloHCT) for AML. Several risk factors (i.e. older age, persistent disease at transplant, adverse cytogenetics, secondary AML, non-myeloablative conditioning regimen) have been identified as predictors for post-transplant AML recurrence. In addition, the adverse prognostic influence of specific mutations (DNMT3, ASXL1, IDH1/2, RUNX1, TET2, TP53 etc.) has been identified in both de novo and secondary AML treated with standard chemotherapy regimens. The impact of these mutations on clinical outcomes following AlloSCT, however, remains largely unexplored. Consequently, we conducted this study to investigate the prognostic role of molecular lesions including metaphase (MC) and SNP array (SNP-A) cytogenetic defects and somatic mutations in patients undergoing AlloHCT. A total of 186 patients were identified who received myeloablative AlloHCT for AML (2000–2010) and had pre-transplant diagnostic leukemic sample available for testing. We performed SNP-A karyotyping and sequencing for RUNX1, DNMT3, TP53, ASXL1, CBL, IDH1/2, NPM1, FLT3ITD and TET2 gene mutations and correlated the results with clinical outcomes following AlloHCT. SNP-A based karyotyping helped to upstage the cytogenetics by inclusion of previously undetected cryptic abnormalities.Cox proportional hazards analysis was used to identify prognostic factors for relapse, relapse free (RFS) and overall survival (OS). Analysis was based on 103 patients (55%) who had data on cytogenetics. Of these 103 patients, 42 (41%) had disease relapse following transplantation and 58 (56%) died within the median follow up of 39 months (range, 8–133) following their myeloablative AlloSCT. The frequencies of mutations were estimated; for example, FLT3, NPM1, DNMT3, ASXL1, IDH1/2, CBL, RUNX1 and TP53 were detected in 18%, 13%, 14%, 9%, 9%, 4%, 2% and 2% of the cases, respectively. Overall, mutations were present in 35% of AML cases, and were exclusive to those with intermediate or favorable risk cytogenetics. Various combinations were encountered, however in those with 2 concomitant mutations, NPM1 was present in all cases. In patients with intermediate risk cytogenetics (n=83) and those with mutational abnormalities the leukemia relapse rate was 40% and 38%, respectively. In particular, among patients harboring NPM1 mutation relapses occurred in those who were positive for either DNMT3 or FLT3ITD. Lower rate of relapse (25%) was observed in patients with ASLX1 and IDH1/2 mutations. In one case of aggressiveTP53 mutation the patient was alive and leukemia free 3 years after her AlloHCT. In multivariable analysis, complex cytogenetics was an independent predictor for inferior RFS (HR=1.97, 95% CI, 1.04–3.7) and OS (HR=1.96, 95% CI, 1.04–3.7).Older age at transplant (per 10 yr increase, HR=1.24, 95% CI, 1.01–1.5) was associated with poorer OS, whereas higher comorbidity score (HR=1.86, 95% CI, 1.04–3.3) was associated with poorer RFS. There was no significant difference in post-transplant outcomes between patients in intermediate risk cytogenetics with detected genetic mutations (excluding isolated NPM1) and those with no detectable mutations. Our preliminary results suggest that myeloablative AlloHCT could minimize the prognostic impact of adverse molecular markers in AML. These mutations potentially serve as important biomarkers in determining the management of AML. Further studies designed to determine their precise role are planned. Disclosures: No relevant conflicts of interest to declare