Cardiac iron overload causes most deaths in ␤-thalassemia major. The efficacy of deferasirox in reducing or preventing cardiac iron overload was assessed in 192 patients with ␤-thalassemia in a 1-year prospective, multicenter study. The cardiac iron reduction arm (n ‫؍‬ 114) included patients with magnetic resonance myocardial T2* from 5 to 20 ms (indicating cardiac siderosis), left ventricular ejection fraction (LVEF) of 56% or more, serum ferritin more than 2500 ng/mL, liver iron concentration more than 10 mg Fe/g dry weight, and more than 50 transfused blood units. The prevention arm (n ‫؍‬ 78) included otherwise eligible patients whose myocardial T2* was 20 ms or more. The primary end point was the change in myocardial T2* at 1 year. In the cardiac iron reduction arm, the mean deferasirox dose was 32.6 mg/kg per day. Myocardial T2* (geometric mean ؎ coefficient of variation) improved from a baseline of 11.2 ms (؎ 40.5%) to 12.9 ms (؎ 49.5%) (؉16%; P < .001). LVEF (mean ؎ SD) was unchanged: 67.4 (؎ 5.7%) to 67.0 (؎ 6.0%) (؊0.3%; P ‫؍‬ .53). In the prevention arm, baseline myocardial T2* was unchanged from baseline of 32.0 ms (؎ 25.6%) to 32.5 ms (؎ 25.1%) (؉2%; P ‫؍‬ .57) and LVEF increased from baseline 67.7 (؎ 4.7%) to 69.6 (؎ 4.5%) (؉1.8%; P < .001). This prospective study shows that deferasirox is effective in removing and preventing myocardial iron accumulation. This study is registered at http://clinicaltrials. gov as NCT00171821. (Blood. 2010;115: 2364-2371)

BackgroundProspective data on cardiac iron removal are limited beyond one year and longer-term studies are, therefore, important. Design and MethodsSeventy-one patients in the EPIC cardiac substudy elected to continue into the 3 rd year, allowing cardiac iron removal to be analyzed over three years. ResultsMean deferasirox dose during year 3 was 33.6±9.8 mg/kg per day. Myocardial T2*, assessed by cardiovascular magnetic resonance, significantly increased from 12.0 ms ±39.1% at baseline to 17.1 ms ±62.0% at end of study (P<0.001), corresponding to a decrease in cardiac iron concentration (based on ad hoc analysis of T2*) from 2.43±1.2 mg Fe/g dry weight (dw) at baseline to 1.80 ±1.4 mg Fe/g dw at end of study (P<0.001). After three years, 68.1% of patients with baseline T2* 10 to <20 ms normalized (≥20 ms) and 50.0% of patients with baseline T2* >5 to <10 ms improved to 10 to <20 ms. There was no significant variation in left ventricular ejection fraction over the three years. No deaths occurred and the most common investigator-assessed drugrelated adverse event in year 3 was increased serum creatinine (n=9, 12.7%). ConclusionsThree years of deferasirox treatment along with a clinically manageable safety profile significantly reduced cardiac iron overload versus baseline and normalized T2* in 68.1% (32 of 47) of patients with T2* 10 to <20 ms.

Background: Health Related Quality of Life (HRQoL) studies on children with chronic illness such as thalassaemia are limited. We conducted the first study to investigate if children with thalassaemia have a lower quality of life in the four dimensions as measured using the PedsQL 4.0 generic Scale Score: physical, emotional, social and role (school) functioning compared to the healthy controls allowing for age, gender, ethnicity and household income.

Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% is efficacious and well-tolerated in people with hemophilia A (PwHA). As some may benefit from higher FVIII troughs, the PROPEL trial compared safety and efficacy of 2 target FVIII trough levels in PwHA with severe disease, aged 12-65 years, annualized bleeding rate ≥2, and previous FVIII treatment. They were randomized to 12 months' pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1-3% (reference arm) or 8-12% (elevated arm). Treatment-adjustment period was in the first 6 months. Primary endpoint: proportion of PwHA (full analysis set [FAS]) with zero total bleeds (all bleeds) during second 6 months. Overall, 115 male PwHA were randomized (N=115, FAS; N=95, per-protocol analysis set [PPAS]). In the 1-3% and 8-12% arms, respectively, point estimates (95% CI) of proportions of PwHA with zero total bleeds were 42% (29-55%) and 62% (49-75%) in FAS (P=0.055) and 40% (27-55%) and 67% (52-81%) in PPAS (P=0.015). Dosing frequency and consumption varied widely in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA. Serious AEs occurred in 7/115 (6%) PwHA, including 1 treatment-related serious AE in 8-12% arm (transient anti-FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms, with no new safety signal in the 8-12% arm vs previous studies. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and also emphasize the importance of personalized treatment. Trial registration: www.ClinicalTrials.gov (#NCT02585960).

Smartphones are becoming increasingly common in both personal and professional spheres. These devices have many features which can be successfully harnessed in healthcare, including rapid access to information, instant communication and improved organisation. In particular, the smartphone's potential as an educational tool is an area which is starting to gain recognition, with a number of institutions providing the device to medical students. However, before more universities follow suit, a better understanding of students' ownership, usage and attitudes relating to smartphones is required. We therefore distributed a questionnaire to clinical medical students at the University of Birmingham, UK, which aimed to fill these gaps in knowledge. Data were obtained from 361 participants, representing a response rate of 32%. Fifty-nine per cent of students owned a smartphone; 37% of these reported using the device to support their learning. Generally students were positive towards the concept of smartphones as future educational aids, with 84% believing the devices would be useful or very useful. However, 64% thought smartphones would be too costly to implement and 62% felt such technology was not in the medical school's interest. Themes which emerged upon analysis of free text supported general findings, with students also mentioning issues such as potential for unprofessional behaviour and dependence upon smartphones. In conclusion, it appears most medical students believe a smartphone would be a useful addition to their education, although financial barriers must be overcome before the device is more universally accepted.

BackgroundThe efficacy of cardiac iron chelation in transfusion-dependent patients has been demonstrated in one-year prospective trials. Since normalization of cardiac T2* takes several years, the efficacy and safety of deferasirox was assessed for two years in patients with β-thalassemia major in the cardiac sub-study of the EPIC trial. Design and MethodsEligible patients with myocardial T2* greater than 5 to less than 20 ms received deferasirox, with the primary endpoint being the change in T2* from baseline to two years. ResultsBaseline myocardial T2* was severe (>5 to <10 ms) in 39 patients, and moderate-to-mild (10 to <20 ms) in 62 patients. Mean deferasirox dose was 33.1±3.7 mg/kg/d in the one-year core study increasing to 36.1±7.7 mg/kg/d during the second year of treatment. Geometric mean myocardial T2* increased from a baseline of 11.2 to 14.8 ms at two years (P<0.001). In patients with moderate-to-mild baseline T2*, an increase was seen from 14.7 to 20.1 ms, with normalization (≥20 ms) in 56.7% of patients. In those with severe cardiac iron overload at baseline, 42.9% improved to the moderate-to-mild group. The incidence of drug-related adverse events did not increase during the extension relative to the core study and included (≥5%) increased serum creatinine, rash and increased alanine aminotransferase. ConclusionsContinuous treatment with deferasirox for two years with a target dose of 40 mg/kg/d continued to remove iron from the heart in patients with β-thalassemia major and mild, moderate and severe cardiac siderosis. (Clinicaltrials.gov identifier: NCT 00171821) Key words: β-thalassemia major, cardiac iron overload, deferasirox, iron chelation, myocardial T2*. Haematologica 2011;96(1):48-54. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Pennell DJ, Porter JB, Cappellini MD, Chan LL, El-Beshlawy A, Aydinok Y, Ibrahim H, Li C-K, Viprakasit V, Elalfy MS, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, and Taher A. Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload.Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload

Malaysia is currently facing an outbreak of COVID-19. We aim to present the first study in Malaysia to report the reproduction numbers and develop a mathematical model forecasting COVID-19 transmission by including isolation, quarantine, and movement control measures. We utilized a susceptible, exposed, infectious, and recovered (SEIR) model by incorporating isolation, quarantine, and movement control order (MCO) taken in Malaysia. The simulations were fitted into the Malaysian COVID-19 active case numbers, allowing approximation of parameters consisting of probability of transmission per contact (β), average number of contacts per day per case (ζ), and proportion of close-contact traced per day (q). The effective reproduction number (Rt) was also determined through this model. Our model calibration estimated that (β), (ζ), and (q) were 0.052, 25 persons, and 0.23, respectively. The (Rt) was estimated to be 1.68. MCO measures reduce the peak number of active COVID-19 cases by 99.1% and reduce (ζ) from 25 (pre-MCO) to 7 (during MCO). The flattening of the epidemic curve was also observed with the implementation of these control measures. We conclude that isolation, quarantine, and MCO measures are essential to break the transmission of COVID-19 in Malaysia.

Introduction: The novel coronavirus infection has become a global threat affecting almost every country in the world. As a result, it has become important to understand the disease trends in order to mitigate its effects. The aim of this study is firstly to develop a prediction model for daily confirmed COVID-19 cases based on several covariates, and secondly, to select the best prediction model based on a subset of these covariates. Methodology: This study was conducted using daily confirmed cases of COVID-19 collected from the official Ministry of Health, Malaysia (MOH) and John Hopkins University websites. An Autoregressive Integrated Moving Average (ARIMA) model was fitted to the training data of observed cases from 22 January to 31 March 2020, and subsequently validated using data on cases from 1 April to 17 April 2020. The ARIMA model satisfactorily forecasted the daily confirmed COVID-19 cases from 18 April 2020 to 1 May 2020 (the testing phase). Results: The ARIMA (0,1,0) model produced the best fit to the observed data with a Mean Absolute Percentage Error (MAPE) value of 16.01 and a Bayes Information Criteria (BIC) value of 4.170. The forecasted values showed a downward trend of COVID-19 cases until 1 May 2020. Observed cases during the forecast period were accurately predicted and were placed within the prediction intervals generated by the fitted model. Conclusions: This study finds that ARIMA models with optimally selected covariates are useful tools for monitoring and predicting trends of COVID-19 cases in Malaysia.