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Perspectives of at-Risk Individuals on Preventive Intervention for Rheumatoid Arthritis: A Mini Review.
No full textThere has been intense research focus on the biological mechanisms underlying the transition from health to disease for rheumatoid arthritis (RA) over recent years, and it is now well established that a state of autoimmunity precedes the development of symptoms for a large proportion of patients. This has led to an increased interest in the identification of at-risk groups and the potential for preventive intervention. The ability of several immunomodulatory agents to delay or prevent RA is under investigation and novel cellular therapies are in development. Preventive approaches are also being assessed in other chronic autoimmune diseases. For example, an anti-CD3 antibody has recently been shown to delay progression to type 1 diabetes in non-diabetic relatives of patients identified as being at high risk. The identification and treatment of individuals as being at risk of a disease where there is a degree of uncertainty around the potential for benefit is socially and ethically challenging. Recently reported difficulties in recruitment to RA prevention trials have underlined the importance of understanding the perspectives of at-risk individuals to identify barriers and facilitators that need to be addressed in order for preventive strategies to be acceptable. Understanding of their preferences for benefits and risks of preventive interventions can inform efficient intervention prioritization, prevention trial design and the development of informational resources for those at risk. In this review we summarize current knowledge of preferences for RA prevention and make recommendations for further research needed to ensure efficient development of preventive therapies and clinical implementation
Comparison of fludarabine-melphalan and fludarabine-treosulfan as conditioning prior to allogeneic hematopoietic cell transplantation-a registry study on behalf of the EBMT Acute Leukemia Working Party.
No full textIn recent years considerable variations in conditioning protocols for allogeneic hematopoietic cell transplantation (allo-HCT) protocols have been introduced for higher efficacy, lower toxicity, and better outcomes. To overcome the limitations of the classical definition of reduced intensity and myeloablative conditioning, a transplantation conditioning intensity (TCI) score had been developed. In this study, we compared outcome after two frequently used single alkylator-based conditioning protocols from the intermediate TCI score category, fludarabine/melphalan 140 mg/m (FluMel) and fludarabine/treosulfan 42 g/m (FluTreo) for patients with acute myeloid leukemia (AML) in complete remission (CR). This retrospective analysis from the registry of the Acute Leukemia Working Party (ALWP) of the European Society of Bone Marrow Transplantation (EBMT) database included 1427 adult patients (median age 58.2 years) receiving either Flu/Mel (n = 1005) or Flu/Treo (n = 422). Both groups showed similar 3-year overall survival (OS) (54% vs 51.2%, p value 0.49) for patients conditioned with FluMel and FluTreo, respectively. However, patients treated with FluMel showed a reduced 3-year relapse incidence (32.4% vs. 40.4%, p value < 0.001) and slightly increased non-relapse mortality (NRM) (25.7% vs. 20.2%, p value = 0.06) compared to patients treated with FluTreo. Our data may serve as a basis for further studies examining the role of additional agents/ intensifications in conditioning prior to allo-HCT
Early oral feeding after pancreatoduodenectomy: a systematic review and meta-analysis.
No full textBACKGROUND
The effect of early oral feeding (EOF) after pancreatoduodenectomy (PD) upon perioperative complications and outcomes is unknown, therefore the aim of this systematic review and meta-analysis was to investigate the effect of EOF on clinical outcomes after PD, such as postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE) and length of stay (LOS).
METHODS
A systematic review and meta-analysis was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance and assimilated evidence from studies reporting outcomes for patients who received EOF after PD compared to enteral tube feeding (EN) or parenteral nutrition (PN).
RESULTS
Four studies reported outcomes after EOF compared to EN/PN after PD and included 553 patients. Meta-analyses showed no difference in rates of CR-POPF (OR 0.74; 95%CI 0.44-1.24; p = 0.25) or DGE (Grade B/C) (OR 0.83; 95%CI 0.31-2.21; p = 0.70). LOS was significantly shorter in the EOF group compared to the EN/PN group (Mean Difference -3.40 days; 95% -6.11-0.70 days; p = 0.01).
CONCLUSION
Current available evidence suggests that EOF after PD is not associated with increased risk of DGE, does not exacerbate POPF and appears to reduce length of stay
Severity of oEsophageal Anastomotic Leak in patients after oesophagectomy: the SEAL score.
No full textBACKGROUND
Anastomotic leak (AL) is a common but severe complication after oesophagectomy. It is unknown how to determine the severity of AL objectively at diagnosis. Determining leak severity may guide treatment decisions and improve future research. This study aimed to identify leak-related prognostic factors for mortality, and to develop a Severity of oEsophageal Anastomotic Leak (SEAL) score.
METHODS
This international, retrospective cohort study in 71 centres worldwide included patients with AL after oesophagectomy between 2011 and 2019. The primary endpoint was 90-day mortality. Leak-related prognostic factors were identified after adjusting for confounders and were included in multivariable logistic regression to develop the SEAL score. Four classes of leak severity (mild, moderate, severe, and critical) were defined based on the risk of 90-day mortality, and the score was validated internally.
RESULTS
Some 1509 patients with AL were included and the 90-day mortality rate was 11.7 per cent. Twelve leak-related prognostic factors were included in the SEAL score. The score showed good calibration and discrimination (c-index 0.77, 95 per cent c.i. 0.73 to 0.81). Higher classes of leak severity graded by the SEAL score were associated with a significant increase in duration of ICU stay, healing time, Comprehensive Complication Index score, and Esophagectomy Complications Consensus Group classification.
CONCLUSION
The SEAL score grades leak severity into four classes by combining 12 leak-related predictors and can be used to the assess severity of AL after oesophagectomy
Effect of obstructive sleep apnoea on retinal microvascular function: a randomised controlled trial.
No full textPURPOSE
Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function.
METHODS
We conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP.
RESULTS
Nineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI - 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP.
CONCLUSIONS
CPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function. ISRCTN 78082983, 23/10/2014, Prospectively registered
Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis.
No full textAlthough anaerobic bacteria exist in abundance in cystic fibrosis (CF) airways, their role in disease progression is poorly understood. We hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes. This is the first study to prospectively investigate viable anaerobic bacteria present in the sputum microbiota and their relationship with long-term outcomes in adults with CF. We performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. We examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV change. The presence of and were associated with a greater annual rate of FEV change; -52.3 ml yr (95 % CI-87.7;-16.9), -67.9 ml yr (95 % CI-115.6;-20.1), respectively. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV decline of -3.7 ml yr (95 % CI: -6.1 to -1.3, =0.003) and -5.3 ml yr (95 % CI: -8.7 to -1.9, =0.002) for each log increment of abundance, respectively. The presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline. The pathogenicity of anaerobic bacteria in the CF airways should be confirmed with further longitudinal prospective studies with a larger cohort of participants
Adjuvant radiotherapy improves long-term survival after resection for gallbladder cancer A population-based cohort study.
No full textBACKGROUND
Data supporting routine use of adjuvant radiotherapy (RT) compared to without RT (noRT) for gallbladder cancer (GBC) is unclear. This study aimed to determine whether RT improves long-term survival following resection for GBC.
METHODS
Patients receiving resection for GBC followed by RT from 2004 to 2016 were identified from the National Cancer Database (NCDB). Patients with survival <6 months were excluded to account for immortal time bias. Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of RT on overall survival.
RESULTS
Of 7514 (77%) noRT and 2261 (23%) RT, 2067 noRT and 2067 RT patients remained after PSM. After matching, RT was associated with improved survival (median: 26.2 vs 21.5 months, p < 0.001), which remained after multivariable adjustment (HR: 0.82, CI: 0.76-0.89, p < 0.001). On multivariable interaction analyses, this benefit persisted irrespective of nodal status: N0 (HR: 0.84, CI: 0.77-0.93), N1 (HR: 0.77, CI: 0.68-0.88), N2/N3 (HR: 0.56, CI: 0.35-0.91), margin status: R0 (HR: 0.85, CI: 0.78-0.93), R1 (HR: 0.78, CI: 0.68-0.88) and use of adjuvant chemotherapy (AC) (HR: 0.67, CI: 0.57-0.79). Benefit with RT were also seen in patients with T2 - T4 disease and in patients undergoing simple and extended cholecystectomy.
CONCLUSION
RT following resection was associated with improved survival in this study, even in margin-negative and node-negative disease. These findings may suggest addition of RT into multimodality therapy for GBC
Allogeneic hematopoietic stem cell transplantation for adult HLH: a retrospective study by the chronic malignancies and inborn errors working parties of EBMT.
No full textHemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in primary, recurrent or progressive HLH, but information about its outcomes in the adult population is limited. We obtained data about 87 adult (≥18 years of age) patients retrospectively reported to the EBMT. The median survival time was 13.9 months. The three and five-year overall survival (OS) was 44% (95% CI 33-54%). Among 39 patients with a follow-up longer than 15 months, only three died. Relapse rate was 21% (95% CI 13-30%), while NRM reached 36% (95% CI 25-46%). Younger patients (<30 years of age) had better prognosis, with an OS of 59% (95% CI 45-73%) at three and five years vs 23% (95% CI 8-37%) for older ones. No difference in survival between reduced and myeloablative conditioning was found. To our knowledge, this is the largest report of adult HLH patients who underwent allo-HSCT. Patients who survive the first period after this procedure can expect a long disease-free survival. Both reduced intensity and myeloablative conditioning have therapeutic potential in adult HLH
The Effect of Telemonitoring (TM) on Improving Adherence with Continuous Positive Airway Pressure (CPAP) in Obstructive Sleep Apnoea (OSA): A Service Improvement Project (SIP).
No full textThe benefits of CPAP demonstrated in clinical trials are difficult to deliver in real life due to the lack of adherence. We analysed the effect of a Telemonitoring (TM)-related intervention on adherence as part of a Service Improvement Project (SIP) analysed as a retrospective cohort study. The 'historical control' (HC) cohort (followed up in conventional clinics) included all patients who commenced on CPAP between 1 February and 30 April 2019 (n = 142). The 'telemonitoring' (TM) cohort included all patients who commenced on CPAP between 1 May and 31 July 2019 (n = 166). Adherence was checked at 30 days (baseline) and 73 days for both cohorts. Wilcoxon-Rank test was used for statistical analysis (results reported as mean ± SEM). Both cohorts had similar adherence at the 30-day baseline, compared to a significantly lower adherence in the HC-cohort at 73 days (55.7 ± 3.0 vs. 51.8 ± 3.2% of days ≥ 4 h: = 0.0072, average usage 255 ± 12.8 vs. 236 ± 13.7 min: = 0.0003). There was a significantly higher adherence in the TM-cohort at 73 days (50.8 ± 2.5 vs. 56.1 ± 2.9% of days ≥ 4 h: = 0.0075; average usage 234 ± 10.4 vs. 252 ± 12.1 min: = 0.0456). Telemonitoring-feedback is effective at improving adherence with CPAP, suggesting its potential beneficial role in the community setting, particularly in the post-COVID reality of increased remote consultations