Examining Treatment Patterns and Real-World Outcomes in Chronic Lymphocytic Leukemia Using Administrative Data in Ontario

Information on the real-world experience of Canadians diagnosed with chronic lymphocytic leukemia (CLL) is limited. This study was conducted to report treatment patterns and outcomes of CLL using Ontario administrative data. A retrospective cohort study was conducted in patients diagnosed with CLL between 1 January 2010 and 31 December 2017 identified in the Ontario Cancer Registry (OCR). Data were accessed using the Institute of Clinical Evaluative Sciences (ICES), which collects various population-level health information. In the Ontario Cancer Registry, 2887 CLL patients receiving treatment and diagnosed between 2010–2017 were identified. Fludarabine, cyclophosphamide and rituximab (FCR) chemoimmunotherapy was most frequently used as a first line, but use declined since ibrutinib and obinutuzumab combinations were funded in 2015. In patients treated with frontline FCR, survival at year one was 89% pre-2015 and 96% post-2015; at year four, survival was 73% and 87%, respectively. Survival in patients treated with frontline chlorambucil was 76% pre-2015 and 75% post-2015 in year 1, and 45% and 56% in year 3. Our analysis shows that, as the treatment landscape for CLL has shifted, use of newer and novel agents as a first line or earlier in the relapsed/refractory setting has resulted in improved survival outcomes.     

Safety and feasibility of same day discharge after per oral endoscopic pyloromyotomy in refractory gastroparesis: a pilot study

Background:Gastroparesis is a debilitating medical condition with limited treatment options. Gastric per-oral pyloromyotomy (G-POEM) has emerged as a promising treatment option with remarkable short-term clinical success shown in multiple studies. While the post-procedure protocol is not standardized across many centers, the majority of the centers observes these patients in the hospital after the procedure for monitoring. In this single-center prospective study, we evaluated the safety and feasibility of same day discharge after the G-POEM procedure.Methods:All the patients with refractory gastroparesis undergoing G-POEM from October 2019 to March 2020 were enrolled. A total of 25 patients were enrolled in the procedure. Based on the pre-defined criteria, patients were either discharged on the same day after the procedure or admitted to the hospital for further observation. The patient and procedure-related data were extracted from the chart review. Univariate analysis was performed (chi-squared test) on categorical variables after organizing categorical variables as numeric counts or percentages. The student t test was performed on continuous variables after reporting as mean and standard deviation. For analysis with a smaller sample size, Fisher exact and Mann–Whitney tests were used.Results:A total of 25 patients were enrolled. The technical success of G-POEM was 100% and clinical success was 80% (20/25) at 1-month follow-up. Of the 25 patients, 9 patients (36%) were discharged on the same day according to the procedure from the recovery unit. Of the remaining 16 patients who were admitted to the hospital post-procedure, 10 (40%) were admitted due to procedure-related causes while other admissions were either pre-planned or due to social reasons. The average Charlson comorbidity index was lower in the same day discharge group (P < 0.05). The number of patients requiring double myotomy was higher in the same day discharge group (P < 0.05). The overall complication rate of G-POEM in the study cohort was 12% (3/25) with all complications being mild without any severe adverse events.Conclusion:G-POEM is a safe and effective method of treatment for refractory GP with higher clinical success in short-term follow-up. The same day discharge after G-POEM is safe and feasible in >50% of patients with close periprocedural monitoring.     

Hepatic Histoplasmosis: An Update

Histoplasma capsulatum is the most common cause of endemic mycosis in developing countries. It is a self-limited and asymptomatic disease in immunocompetent individuals but remains a frequent cause of opportunistic infection in patients with compromised immune status. Liver involvement as a part of disseminated histoplasmosis is well known. However, liver infection as a primary manifestation of histoplasmosis without evidence of primary lung involvement is rare. In conclusion, clinicians should be aware of isolated histoplasmosis affecting the hepatobiliary system, and careful evaluation is warranted to confirm the diagnosis. Given the appropriate clinical context, histoplasmosis should be considered in both immunocompetent and immunocompromised patients, regardless of pulmonary symptoms, in non endemic as well as endemic areas.     

Human neutrophil antigen 3 genotype impacts neutrophil-mediated endothelial cell cytotoxicity in a two-event model of TRALI

BackgroundAntibodies against human neutrophil antigen (HNA)-3a are associated with severe cases of transfusion-related acute lung injury (TRALI). The HNA-3 system is located on choline transporter-like 2 (CTL-2) protein. CTL-2 is encoded by the gene SLC44A2 and a single-nucleotide polymorphism c.461G>A results in two antigens: HNA-3a and HNA-3b. Three HNA-3 genotypes/ phenotypes exist: HNA-3aa, HNA-3bb, and HNA-3ab. Two different pathways of anti-HNA-3a TRALI have been described: a two-hit neutrophil-dependent pathway and a one-hit neutrophil-independent pathway. However, it is not clear whether HNA-3ab heterozygous patients have a lower risk of anti-HNA-3a-mediated TRALI compared to HNA-3aa homozygous patients.Materials and methodsHealthy volunteers were genotyped for HNA-3 by real-time polymerase chain reaction, and phenotyped for HNA-3a by granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT) against two donor sera containing anti-HNA-3a antibodies. The two sera were also used in in vitro models of human pulmonary microvascular endothelial cell (HLMVEC) cytotoxicity to investigate pathways of TRALI development.ResultsFor both anti-HNA-3a sera, GIFT results matched the genotype, with a lower GIFT ratio for HNA-3ab neutrophils compared to HNA-3aa neutrophils, whereas GAT results showed no difference in agglutination. HLMVEC cytotoxicity was not observed in a one-hit neutrophil-independent model but was observed in a two-hit neutrophil-dependent model. Differences in cytotoxicity were observed between the two anti-HNA-3a sera used. Consistent with reduced HNA-3a antigen density as measured by GIFT, HNA-3ab neutrophils mediated less HLMVEC cytotoxicity than HNA-3aa neutrophils.ConclusionHNA-3 genotype and HNA-3a antigen expression impacted the severity of anti-HNA-3a-mediated HLMVEC cytotoxicity in a two-hit neutrophil-dependent model of TRALI. Different HNA-3a antibodies might also impact the magnitude of HLMVEC cytotoxicity.     

Using structural equation modeling to predict Indian people's attitudes and intentions towards COVID-19 vaccination

Background and aimUnderstanding people's attitudes towards Covid-19 vaccination is crucial to the successful implementation of a vaccination program. Hence this research study seeks to identify critical factors influencing Indian people's attitudes and intentions to take up Covid-19 vaccinations.MethodsAn online questionnaire was administered to a sample (n = 254) drawn from Indian population, to assess the impact of perceived benefits, risk perceptions, social media exposure, social norms, and trust associated with Covid-19 vaccines on people's attitudes towards Covid-19 vaccines and their intentions to take up the Covid-19 vaccinations.ResultsThe findings showed that the perceived benefits, social norms, and trust correlated significantly with people's attitudes towards Covid-19 vaccinations. In contrast, risk perceptions and social media exposure showed an insignificant influence on people's attitudes towards Covid-19 vaccinations. Social norms, trust, and people's attitudes towards the Covid-19 vaccinations are significantly correlated with their intentions to take up Covid-19 vaccinations. On the contrary, social media exposure was found to have an insignificant influence on people's intentions to take up Covid-19 vaccinations.ConclusionParticipants' intentions to take up Covid-19 vaccinations was influenced mainly by their attitudes and perceptions of Covid-19 vaccines in general, which strongly confirms the importance of various dimensions (perceived benefits, trust, social norms) of Covid-19 vaccines in cultivating Covid-19 vaccination acceptance among participants’.