METHODS: We reviewed the literature on prophylaxis in haemophilia since its inception in the 1950s to the present, the development of more and less intense factor prophylaxis regimens and their outcomes and additionally the published outcomes of prophylaxis with low dose emicizumab.
RESULTS: What these experiences collectively show is that low dose emicizumab does result in significant benefits to patients whilst being much less expensive than a "one size fits all" emicizumab prophylaxis approach. We also took note that some non-factor therapies still in development are individualized given that high doses of these can potentially put patients at risk.
CONCLUSIONS: Prophylaxis is now clearly accepted as standard of care for PWH with a severe phenotype but now in a very short time a large assortment of different treatment options for prophylaxis have become/are becoming available and the haemophilia community will need to determine how to best use these recognizing that no 'one treatment fits all'.
METHOD: We retrospectively reviewed 38 patients who had AIBG and uncemented cup reconstruction of the acetabulum performed between 2008 and 2021 for complex primary and revision surgery. Graft incorporation, radiological loosening and cup migration were evaluated in follow-up X-rays.
RESULT: There were 24 complex primary and 14 revision total hip arthroplasty. Autografts were used in 10 hips with smaller defects, while 28 hips with larger defects required frozen irradiated femoral head allografts. Using Paprosky classification to evaluate acetabular defects; 8 patients were classified as 2A, 12 as 2B, 7 as 2C, 8 as 3A and 3 as 3B. The Kaplan-Meier survival rate for AIBG with uncemented cups in our series is 89.70% in 10 years. Acetabular cup position was anatomically restored in all autograft AIBG cases and in 25 out of 28 in the allograft group. The mean pre-operative Oxford Hip Score (OHS) was 19 (range 10-24) and post-operative OHS was 39 (range 21-48) (p
METHODS: A series of 400 consecutive patients (416 hips) who underwent navigated (Brainlab) cementless Total Hip Arthroplasty (THA) in 2022 (Corail or Actis stem DePuy Synthes) via a direct anterior approach (DAA) was analyzed. Preoperative data were collected based on patients' demographics, radiographic information [critical trochanteric angle (CTA), centrum collum diaphyseal (CCD) angle, greater trochanter overhang, femoral neck resection angle, femoral neck resection height and Door classification], and these were correlated with the postoperative stem position. Univariable and multivariable linear regression were carried out to determine significant factors that contribute to varus and valgus stem malalignment.
RESULTS: With the DAA approach, 56.5 % of stems were placed in an optimal neutral position, 38.4 % were in acceptable position of 0.1°-2° varus/valgus and only 5 % had a deviation larger than 2° varus/valgus. The critical trochanteric angle (CTA) was statistically significant in determining varus stem placement whereas centrum collum diaphyseal angle (CCD) was found to affect valgus stem malpositioning. All other factors have shown no relevant effect on stem placement using stepwise regression method.
CONCLUSION: In DAA, 95 % of stems were found in a varus/valgus position of 2° or less. In pre-operative measurement, only femoral morphology (e.g. CTA & CCD) were found to be relevant, affecting varus/valgus stem malposition. All other tested modifiable and non-modifiable factors had no significant effect. Therefore, pre-OP templating including measurement of CTA and CCD, intra-operative assessment as well as proper operative techniques are paramount to prevent excessive varus/valgus mal-position of femoral stem in DAA.
AIM: The aim of this study was to determine the characteristics of medication complexity and polypharmacy and determine their relationship with drug-related problems (DRP) and control of iron overload in transfusion-dependent thalassaemia patients.
METHOD: Data were derived from a cross-sectional observational study on characteristics of DRPs conducted at a Malaysian tertiary hospital. The medication regimen complexity index (MRCI) was determined using a validated tool, and polypharmacy was defined as the chronic use of five or more medications. The receiver operating characteristic curve analysis was used to determine the optimal cut-off value for MRCI, and logistic regression analysis was conducted.
RESULTS: The study enrolled 200 adult patients. The MRCI cut-off point was proposed to be 17.5 (Area Under Curve = 0.722; sensitivity of 73.3% and specificity of 62.0%). Approximately 73% and 64.5% of the patients had polypharmacy and high MRCI, respectively. Findings indicated that DRP was a full mediator in the association between MRCI and iron overload.
CONCLUSION: Transfusion-dependent thalassaemia patients have high MRCI and suboptimal control of iron overload conditions in the presence of DRPs. Thus, future interventions should consider MRCI and DRP as factors in serum iron control.
METHODS: This was a retrospective study with prospectively collected data between 2016 and 2020. Data collected were age, gender, types of graft used, range of movement, posterior drawer test grade, KOOS score, Lysholm knee scoring scale, and post-operative complications. All patients underwent pre- and post-operative PCL rehabilitation.
RESULTS: A total of 36 patients (26 males and 10 females) were identified from our database. The mean age was 35.2 years. Mean time from injury to surgery was 20 months. Mean follow-up was 41.2 months (range, 13-72 months). Twenty cases involved multi-ligament injuries and another 16 patients had isolated PCL injury. Post-operative mean posterior drawer test grade improved from 2.7 to 0.7 (p
METHODS: The performance of a custom, in-house designed 22-gene NGS panel was technically validated using reference standards across two independent replicate runs. The panel was subsequently used to screen a total of 10 clinical MPN samples (ET n = 3, PV n = 3, PMF n = 4). The resulting NGS data was then analysed via a bioinformatics pipeline.
RESULTS: The custom NGS panel had a detection limit of 1% variant allele frequency (VAF). A total of 20 unique variants with VAFs above 5% (4 of which were putatively novel variants with potential biological significance) and one pathogenic variant with a VAF of between 1 and 5% were identified across all of the clinical MPN samples. All single nucleotide variants with VAFs ≥ 15% were confirmed via Sanger sequencing.
CONCLUSIONS: The high fidelity of the NGS analysis and the identification of known and novel variants in this study cohort support its potential clinical utility in the management of MPNs. However, further optimisation is needed to avoid false negatives in regions with low sequencing coverage, especially for the detection of driver mutations in MPL.
METHODS: The 307 open-label extension (OLE) study (NCT03531255) is a non-randomized, multicenter extension study of long-term safety and efficacy of pegcetacoplan in adult patients with PNH who completed a pegcetacoplan parent study. All patients received pegcetacoplan. Outcomes at the 48-week data cutoff (week 48 of 307-OLE or August 27, 2021, whichever was earlier) are reported. Hemoglobin concentrations, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores, and transfusion avoidance were measured. Hemoglobin > 12 g/dL and sex-specific hemoglobin normalization (i.e., male, ≥ 13.6 g/dL; female, ≥ 12 g/dL) were assessed as percentage of patients with data available and no transfusions 60 days before data cutoff. Treatment-emergent adverse events, including hemolysis, were reported.
RESULTS: Data from 137 patients with at least one pegcetacoplan dose at data cutoff were analyzed. Mean (standard deviation [SD]) hemoglobin increased from 8.9 (1.22) g/dL at parent study baseline to 11.6 (2.17) g/dL at 307-OLE entry and 11.6 (1.94) g/dL at data cutoff. At parent study baseline, mean (SD) FACIT-Fatigue score of 34.1 (11.08) was below the general population norm of 43.6; scores improved to 42.8 (8.79) at 307-OLE entry and 42.4 (9.84) at data cutoff. In evaluable patients, hemoglobin > 12 g/dL occurred in 40.2% (43 of 107) and sex-specific hemoglobin normalization occurred in 31.8% (34 of 107) at data cutoff. Transfusion was not required for 114 of 137 patients (83.2%). Hemolysis was reported in 23 patients (16.8%). No thrombotic events or meningococcal infections occurred.
CONCLUSION: Pegcetacoplan sustained long-term improvements in hemoglobin concentrations, fatigue reduction, and transfusion burden. Long-term safety findings corroborate the favorable profile established for pegcetacoplan.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03531255.