Differential effects of iron chelators on iron burden and long-term morbidity and mortality outcomes in a large cohort of transfusion-dependent β-thalassemia patients who remained on the same monotherapy over 10 years

We conducted a retrospective cohort study on 663 transfusion-dependent β-thalassemia patients receiving the same iron chelation monotherapy with deferoxamine, deferiprone, or deferasirox for up to 10 years (median age 31.8 years, 49.9 % females). Patients on all three iron chelators had a steady and significant decline in serum ferritin over the 10 years (median deferoxamine: -170.7 ng/mL, P = 0.049, deferiprone: -236.7 ng/mL, P = 0.001; deferasirox: -323.7 ng/mL, P < 0.001) yet had no significant change in liver iron concentration or cardiac T2*; while noting that patients generally had low hepatic and cardiac iron levels at study start. Median absolute, relative, and normalized changes were generally comparable between the three iron chelators. Patients receiving deferasirox had the highest morbidity and mortality-free survival probability among the three chelators, although the difference was only statistically significant when compared with deferoxamine (P = 0.037). On multivariate Cox regression analysis, there was no significant association between iron chelator type and the composite outcome of morbidity or mortality. In a real-world setting, there is comparable long-term iron chelation effectiveness between the three available iron chelators for patients with mild-to-moderate iron overload

Revisiting iron overload status and change thresholds as predictors of mortality in transfusion-dependent β-thalassemia: a 10-year cohort study

Data on iron overload status and change thresholds that can predict mortality in patients with transfusion-dependent β-thalassemia (TDT) are limited. This was a retrospective cohort study of 912 TDT patients followed for up to 10 years at treatment centers in Italy (median age 32 years, 51.6% female). The crude mortality rate was 2.9%. Following best-predictive threshold identification through receiver operating characteristic curve analyses, data from multivariate Cox-regression models showed that patients with Period Average Serum Ferritin (SF) > 2145 vs ≤ 2145 ng/mL were 7.1-fold (P < 0.001) or with Absolute Change SF > 1330 vs ≤ 1330 ng/mL increase were 21.5-fold (P < 0.001) more likely to die from any cause. Patients with Period Average Liver Iron Concentration (LIC) > 8 vs ≤ 8 mg/g were 20.2-fold (P < 0.001) or with Absolute Change LIC > 1.4 vs ≤ 1.4 mg/g increase were 27.6-fold (P < 0.001) more likely to die from any cause. Patients with Index (first) cardiac T2* (cT2*) < 27 vs ≥ 27 ms were 8.6-fold (P < 0.001) more likely to die from any cause. Similarly, results at varying thresholds were identified for death from cardiovascular disease. These findings should support decisions on iron chelation therapy by establishing treatment targets, including safe iron levels and clinically meaningful changes over time

Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management

Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines. In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease‐specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes

Preoperative Behavioural Intervention versus standard care to Reduce Drinking before elective orthopaedic Surgery (PRE-OP BIRDS):Protocol for a multicentre pilot randomised controlled trial

Background Evidence suggests that increased preoperative alcohol consumption increases the risk of postoperative complications; therefore, a reduction or cessation in alcohol intake before surgery may reduce perioperative risk. Preoperative assessment presents an opportunity to intervene to optimise patients for surgery. This multicentre, two-arm, parallel group, individually randomised controlled trial will investigate whether a definitive trial of a brief behavioural intervention aimed at reducing preoperative alcohol consumption is feasible and acceptable to healthcare professionals responsible for its delivery and the preoperative elective orthopaedic patient population. Methods Screening will be conducted by trained healthcare professionals at three hospitals in the North East of England. Eligible patients (those aged 18 or over, listed for elective hip or knee arthroplasty surgery and scoring 5 or more or reporting consumption of six or more units on a single occasion at least weekly on the alcohol screening tool) who enrol in the trial will be randomised on a one-to-one non-blinded basis to either treatment as usual or brief behavioural intervention delivered in the pre-assessment clinic. Patients will be followed up 1–2 days pre-surgery, 1–5 days post-surgery (as an in-patient), 6 weeks post-surgery, and 6 months post intervention. Feasibility will be assessed through rates of screening, eligibility, recruitment, and retention to 6-month follow-up. An embedded qualitative study will explore the acceptability of study methods to patients and staff. Discussion This pilot randomised controlled trial will establish the feasibility and acceptability of trial procedures reducing uncertainties ahead of a definitive randomised controlled trial to establish the effectiveness of brief behavioural intervention to reduce alcohol consumption in the preoperative period and the potential impact on perioperative complications