15 results on '"Alina Sadaf"'
Search Results
2. Hyperplastic callus formation in congenital insensitivity to pain: A masquerader of osteosarcoma
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Maha Anwar, Maha Rashid Malik, Shaarif Bashir, Usman Hassan, and Alina Sadaf
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Osteosarcoma ,Congenital insensitivity to pain with anhidrosis ,Hyperplastic callus formation ,Hereditary sensory and autonomic neuropathy type IV ,Pediatrics ,RJ1-570 - Abstract
Background: Congenital insensitivity to pain (CIP) is a rare genetic disorder characterized by the inability to experience pain. Unrecognized, repeated injuries may result in poorly healed fractures with hyperplastic callus formation, auto-amputation of digits, and osteomyelitis. In addition, the loss of joint proprioception leads to neuropathic osteoarthropathy (Charcot joints). Case report: A child with a progressively increasing swelling of the left proximal tibia and an aggressive bone lesion on imaging was suspected to have osteosarcoma. The diagnosis of hyperplastic callus formation was established through a multidisciplinary approach with imaging and repeat tissue biopsy. Conclusion: In the context of CIP, malignant bone tumors, including osteosarcoma are a differential diagnosis and require a review of history, examination, radiology and histology. more...
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- 2023
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3. Automated Oxygen Gradient Ektacytometry: A Novel Biomarker in Sickle Cell Anemia
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Alina Sadaf, Katie G. Seu, Elizabeth Thaman, Rose Fessler, Diamantis G. Konstantinidis, Holly A. Bonar, Jennifer Korpik, Russell E. Ware, Patrick T. McGann, Charles T. Quinn, and Theodosia A. Kalfa
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sickle cell anemia ,erythrocyte ,oxygen gradient ektacytometry ,oxygenscan ,fetal hemoglobin ,F-cell ,Physiology ,QP1-981 - Abstract
Sickle cell anemia (SCA) is a hereditary hemoglobinopathy with a variable phenotype. There is no single biomarker that adequately predicts disease severity and can be used to monitor treatment response in patients in clinical trials and clinical care. The use of clinical outcomes, such as vaso-occlusive crises (VOC), requires long and expensive studies, sometimes with inconclusive results. To address these limitations, there are several biomarkers under study to improve the ability to predict complications and assess treatment response in both clinical and research settings. Oxygen gradient ektacytometry, also called as oxygenscan, is an assay that measures the effects of deoxygenation and reoxygenation on red blood cell (RBC) deformability and is gaining popularity in SCA research, because it captures the dynamic sickling capacity of a patient’s RBCs as they are subjected to an oxygen gradient under steady shear stress. We describe here the oxygenscan methodology and evaluate the correlation between oxygenscan parameters and more well-known biomarkers of SCA such as fetal hemoglobin (HbF), F-cells, and dense red blood cells (DRBCs). Our data indicate that the oxygenscan curve is affected by all these parameters and the result incorporates the effects of %HbF, %F-cells, RBC hydration, and RBC membrane deformability. more...
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- 2021
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4. Novel ARHGAP23‐FER fusion in a metastatic spindle cell–predominant neoplasm with a myofibroblastic phenotype and a sustained metabolic response to lorlatinib
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Janos Sumegi, Katelyn Ferguson, Sara Szabo, Joel I. Sorger, Julia A. Bridge, Alina Sadaf, and Joseph G. Pressey
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Cancer Research ,Lactams ,business.industry ,Cell ,Aminopyridines ,medicine.disease ,Lorlatinib ,Phenotype ,medicine.anatomical_structure ,Oncology ,Neoplasms ,Cancer research ,Humans ,Pyrazoles ,Medicine ,Neoplasm ,business - Published
- 2021
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5. Evaluation of Dosage and Food Effect on L-Glutamine Exposure for Sickle Cell Anemia: A Population Pharmacokinetic Analysis
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Min Dong, Alina Sadaf, Alexander A. Vinks, Russell E. Ware, and Charles T. Quinn
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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6. L-glutamine for sickle cell disease: Knight or pawn?
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Alina Sadaf and Charles T. Quinn
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Glutamine ,Cell ,Anemia, Sickle Cell ,Disease ,030204 cardiovascular system & hematology ,Pharmacology ,Nitric Oxide ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,030212 general & internal medicine ,chemistry.chemical_classification ,Clinical Trials as Topic ,Reactive oxygen species ,Chemistry ,medicine.disease ,Glutathione ,Sickle cell anemia ,Pathophysiology ,Amino acid ,Intestines ,medicine.anatomical_structure ,Minireview ,Oxidative stress - Abstract
Oxidative stress is an important contributor to the pathophysiology of sickle cell disease. The pathways involved are complex and interlinked. L-glutamine is an amino acid with myriad roles in the body, including the synthesis of antioxidants, such as reduced glutathione and the cofactors NAD(H) and NADP(H), as well as nitric oxide—so it has therapeutic potential as an antioxidant. However, the relative impact of L-glutamine on the redox environment in red blood cells in sickle cell disease is not fully understood, and there are few therapeutic trials in sickle cell disease. Following the FDA approval of L-glutamine for sickle cell disease, more research is still needed to understand its clinical effects and role in therapy.Impact statementL-glutamine has been recently approved by the FDA for the prevention of acute complications in sickle cell disease (SCD). However, there are many gaps in our understanding of the biologic role of glutamine and its therapeutic implications in SCD. This review summarizes the pre-clinical and clinical evidence that can inform clinical decision-making and future research on glutamine therapy in SCD patients. more...
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- 2020
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7. Automated Oxygen Gradient Ektacytometry: A Novel Biomarker in Sickle Cell Anemia
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Alina Sadaf, Katie G. Seu, Elizabeth Thaman, Rose Fessler, Diamantis G. Konstantinidis, Holly A. Bonar, Jennifer Korpik, Russell E. Ware, Patrick T. McGann, Charles T. Quinn, and Theodosia A. Kalfa
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0301 basic medicine ,Treatment response ,medicine.medical_specialty ,fetal hemoglobin ,Oxygen gradient ,Physiology ,red blood cell ,lcsh:Physiology ,03 medical and health sciences ,0302 clinical medicine ,Disease severity ,sickle cell anemia ,Physiology (medical) ,Internal medicine ,Fetal hemoglobin ,Methods ,Medicine ,F-cell ,lcsh:QP1-981 ,business.industry ,oxygen gradient ektacytometry ,dense red blood cells ,medicine.disease ,Sickle cell anemia ,Clinical trial ,Red blood cell ,030104 developmental biology ,medicine.anatomical_structure ,oxygenscan ,030220 oncology & carcinogenesis ,Cardiology ,Biomarker (medicine) ,erythrocyte ,business - Abstract
Sickle cell anemia (SCA) is a hereditary hemoglobinopathy with a variable phenotype. There is no single biomarker that adequately predicts disease severity and can be used to monitor treatment response in patients in clinical trials and clinical care. The use of clinical outcomes, such as vaso-occlusive crises (VOC), requires long and expensive studies, sometimes with inconclusive results. To address these limitations, there are several biomarkers under study to improve the ability to predict complications and assess treatment response in both clinical and research settings. Oxygen gradient ektacytometry, also called as oxygenscan, is an assay that measures the effects of deoxygenation and reoxygenation on red blood cell (RBC) deformability and is gaining popularity in SCA research, because it captures the dynamic sickling capacity of a patient’s RBCs as they are subjected to an oxygen gradient under steady shear stress. We describe here the oxygenscan methodology and evaluate the correlation between oxygenscan parameters and more well-known biomarkers of SCA such as fetal hemoglobin (HbF), F-cells, and dense red blood cells (DRBCs). Our data indicate that the oxygenscan curve is affected by all these parameters and the result incorporates the effects of %HbF, %F-cells, RBC hydration, and RBC membrane deformability. more...
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- 2020
8. Pharmacokinetics of L-Glutamine (Endari) in Pediatric and Adult Sickle Cell Disease Patients: A Phase 4, Open-Label, Single-Center Study
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Amanda Pfeiffer, Charles T. Quinn, Teresa Latham, Russell E. Ware, Min Dong, Alina Sadaf, and Alexander A. Vinks
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business.industry ,Immunology ,Cell ,Cell Biology ,Hematology ,Disease ,Pharmacology ,Single Center ,Biochemistry ,medicine.anatomical_structure ,Pharmacokinetics ,Phase (matter) ,L-glutamine ,Medicine ,Open label ,business - Abstract
Introduction: L-glutamine (Endari ®, Emmaus Medical, Inc.) is an amino acid approved for the treatment of sickle cell disease (SCD) by the United States Food and Drug Association (FDA) after 2 clinical trials demonstrated a reduction in painful episodes and hospitalizations. L-glutamine has many roles, including de novo synthesis of intracellular glutathione that may protect sickle erythrocytes from oxidant injury. Despite its licensure, the pharmacokinetics (PK) of multi-dose oral L-glutamine for SCD have not been studied. Methods: We conducted a dose-escalation PK trial from January to June 2021 (NCT04684381) on 3 cohorts with 4 participants each: pediatric SCD patients (0 - 18 y, cohort 1), adult SCD patients (>18 y, cohort 2), and adult healthy volunteers (>18 y, cohort 3). There were 4 weekly study visits to assess 3 ascending dose levels (Figure 1). For each visit, participants arrived in the research clinic after an overnight fast. Plasma L-glutamine and other amino acid levels were obtained before and after oral L-glutamine doses at each visit and quantified by ion exchange chromatography. On study visit 1, a dose of 0.1 g/kg of L-glutamine was administered and amino acids were measured at 30±5, 60±10, 120±15, 180±15 and 240±20 minutes after the dose. The procedure was repeated in the afternoon after a standardized meal. On study visit 2, the dose was increased to 0.3 g/kg twice daily (approximate FDA-approved dosing). On study visit 3, a single oral dose of 0.6 g/kg (once daily dosing) was given for fasting PK levels, and on study visit 4 the 0.6 g/kg dose was given with a standardized meal. After the first 3 study visits, participants continued L-glutamine at the corresponding dose level at home and completed a daily phone survey to document adherence and adverse events. Results: Baseline characteristics are summarized in Table 1. Baseline L-glutamine levels similar across the three study cohorts (Table 1). One participant from cohort 1 withdrew during study visit 1 and was replaced. Another participant from cohort 2 was withdrawn due to hospitalization for severe anemia and was replaced. One participant from cohort 3 did not complete visit 4 due to dyspepsia. Non-compartmental PK analysis (NCA) was conducted using Phoenix WinNonlin® Professional Version 8.4 (Certara, NJ, US; Figure 2). After oral administration, L-glutamine plasma levels peaked (T max) at an average (mean ± SD) of 1.2 ± 0.9 hours. Compared to doses 0.1 g/kg and 0.3 g/kg, the T max was later for 0.6 g/kg (p The most common grade 2 adverse events were dyspepsia and headache (3 instances each). There was no significant elevation in ammonia levels, and plasma concentrations of the metabolite L-glutamate was similar to L-glutamine (Figure 2). Conclusions: This is the first multi-dose PK study of L-glutamine (Endari) for SCD. Daily dosing was overall well-tolerated, with rapid absorption of 0.1 and 0.3 g/kg doses and no drug accumulation. The highest 0.6 g/kg dose was limited by palatability and featured slower and saturable absorption, so further dose escalation is likely not feasible. Ongoing analyses include possible food-drug interactions and PK-pharmacodynamic (PK-PD) studies to identify salutary effects on erythrocytes. Our findings will help inform the proper dosing of L-glutamine for patients with SCD, and potentially permit individualized PK-guided dosing to maximize treatment benefits. This was an investigator-initiated trial funded by Emmaus Medical, Inc. Figure 1 Figure 1. Disclosures Sadaf: Emmaus Medical, Inc: Research Funding. Ware: Bristol Myers Squibb: Research Funding; Addmedica: Research Funding; Hemex Health: Research Funding; Nova Laboratories: Research Funding; Novartis: Other: DSMB Chair; Editas: Other: DSMB Chair. Quinn: Emmaus Medical: Research Funding; Novo Nordisk: Consultancy; Aruvant: Research Funding; Forma Therapeutics: Consultancy. OffLabel Disclosure: Endari (L-glutamine) is FDA approved for the treatment of Sickle Cell Disease at a dose of 0.3 g/kg. However, in our pharmacokinetic study we tested doses 0.1, 0.3 and 0.6 g/kg. more...
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- 2021
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9. Rapid and automated quantitation of dense red blood cells: A robust biomarker of hydroxyurea treatment response
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Charles T. Quinn, Theodosia A. Kalfa, Patrick T. McGann, Jennifer Korpik, Punam Malik, Mary Reynaud, Amanda Pfeiffer, Alina Sadaf, Russell E. Ware, and Omar Niss
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Male ,Treatment response ,Erythrocytes ,Adolescent ,Hemoglobin, Sickle ,Anemia, Sickle Cell ,Article ,Antisickling Agents ,medicine ,Humans ,Hydroxyurea ,Child ,Molecular Biology ,business.industry ,Infant ,Cell Biology ,Hematology ,medicine.disease ,Sickle cell anemia ,Child, Preschool ,Cancer research ,Molecular Medicine ,Biomarker (medicine) ,Female ,business ,Biomarkers - Published
- 2021
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10. Rapid and Automated Quantitation of Dense Red Blood Cells: A Robust Biomarker of Therapeutic Response to Early Initiation of Hydroxyurea in Young Children with Sickle Cell Anemia
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Alina Sadaf, Theodosia A. Kalfa, Russell E. Ware, Charles T. Quinn, Amanda Pfeiffer, Punam Malik, Jennifer Korpik, Patrick T. McGann, Mary Reynaud, and Omar Niss
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business.industry ,Immunology ,Cancer research ,Medicine ,Biomarker (medicine) ,Cell Biology ,Hematology ,business ,medicine.disease ,Biochemistry ,Early initiation ,Sickle cell anemia - Abstract
Introduction: Hydroxyurea has well-described clinical and laboratory benefits in sickle cell anemia (SCA). Traditionally, hemoglobin concentration (Hb) and fetal hemoglobin (HbF) are used to assess treatment response, but these aggregate parameters do not fully capture the range of erythrocyte abnormalities in SCA. Dense red blood cells (DRBCs) are defined as RBCs with density >1.11 g/mL as measured by density-gradient fractionation methods, which are tedious and require technical expertise. This subpopulation of dehydrated RBCs has been associated with increased SCA severity but has not been extensively studied in children. Here we describe the utility of rapid, automated DRBC quantitation and show that the percent of DRBCs (%DRBCs) is a robust biomarker of hydroxyurea response in children with SCA. Methods: The Therapeutic Response Evaluation and Adherence Trial (TREAT, NCT02286154) was a single-center prospective study that demonstrated individualized, pharmacokinetic (PK)-guided hydroxyurea dosing in young patients (mean age 12.1 months at initiation) results in robust and sustained HbF levels >30-40% for most adherent patients. The longitudinal follow-up phase of TREAT aims to comprehensively evaluate hematologic parameters and organ function to demonstrate the long-term benefits of this treatment strategy. During clinic visits (every 3-6 months), TREAT participants had complete blood counts (CBCs) with the ADVIA® 2120i system. This automated analyzer quantifies hyperchromic RBCs within seconds by directly measuring cell hemoglobin concentration, where DRBCs are known to correspond to RBCs with a measured MCHC >41 g/dL. Data were analyzed at baseline and after at least 6 months of hydroxyurea therapy (M≥6). α- and β-globin genotypes were determined for all patients. Results: Thirty-three TREAT participants had ADVIA data available for analysis (Table). All had homozygous SCA except one with sickle-β0-thalasemia; 17 (51.5%) were male. The median age at hydroxyurea initiation was 10.3 months (mean 26.1 months; range 6 months - 17 years). The median duration of hydroxyurea therapy was 27.7 months (mean 31.5). At baseline, median %DRBCs was 2.1%. Baseline %DRBCs were directly correlated with age at initiation of hydroxyurea (p=0.022) and inversely correlated with baseline HbF (p=0.001). After initiation of hydroxyurea (M≥6), there was a 47.6% reduction in %DRBCs (p=0.001). Median %DRBCs at M≥6 was directly correlated with absolute reticulocyte (ARC) (p=0.002), absolute neutrophil (ANC) (p=0.003) and platelet counts (p Conclusions: DRBCs can be rapidly quantified without the tedium of classical density-gradient fractionation methods using the automated ADVIA 2120i hematology analyzer, which directly measures hyperchromic RBCs. These data from TREAT demonstrate the feasibility of serial %DRBC measurements in clinical trials and clinical practice. TREAT participants had low baseline DRBCs compared to untreated adult SCA patients (reported mean ≈12%), reflecting the young age of these patients. Nevertheless, there was a significant decline in %DRBCs with treatment that correlated strongly with the known laboratory benefits of hydroxyurea. In conclusion, automated DRBC measurements are a robust biomarker that can be incorporated in a panel of laboratory measurements of response to hydroxyurea (and severity of SCA). A larger, multicenter study of PK-guided hydroxyurea therapy (HOPS, NCT03789591) is currently underway in 11 US sickle cell centers and will provide generalizable data on DRBC responses with optimal hydroxyurea therapy. Disclosures Malik: Aruvant Sciences, Forma Therapeutics, Inc.: Consultancy; Aruvant Sciences, CSL Behring: Patents & Royalties. Kalfa:Agios Pharmaceuticals, Inc: Consultancy, Research Funding; Forma Therapeutics, Inc: Research Funding. more...
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- 2020
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11. Microscope diagnosis of MYH9-related thrombocytopenia
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Russell E. Ware and Alina Sadaf
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Pathology ,medicine.medical_specialty ,Microscope ,Myh9 gene ,business.industry ,Immunology ,MEDLINE ,Cell Biology ,Hematology ,Biochemistry ,law.invention ,law ,medicine ,business - Published
- 2021
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12. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia
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Jai K Das, Babar Hasan, Najveen Alvi, Alina Sadaf, and Steven D. Colan
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Adult ,Medicine General & Introductory Medical Sciences ,medicine.medical_specialty ,Iron Overload ,Time Factors ,Adolescent ,Iron ,Cardiomyopathy ,030204 cardiovascular system & hematology ,Placebo ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Pharmacology (medical) ,Blood Transfusion ,030212 general & internal medicine ,Amlodipine ,Chelation therapy ,Adverse effect ,Child ,Randomized Controlled Trials as Topic ,Ejection fraction ,business.industry ,Myocardium ,beta-Thalassemia ,Transfusion Reaction ,medicine.disease ,Calcium Channel Blockers ,Combined Modality Therapy ,Confidence interval ,Chelation Therapy ,Liver ,Heart failure ,Ferritins ,Cardiology ,Female ,business ,Cardiomyopathies ,medicine.drug - Abstract
Background Beta thalassaemia is a common inherited blood disorder. The need for frequent blood transfusions in this condition poses a difficult problem to healthcare systems. The most common cause of morbidity and mortality is cardiac dysfunction from iron overload. The use of iron chelation therapy has reduced the severity of systemic iron overload but specific, non-toxic treatment is required for removal of iron from the myocardium. Objectives To assess the effects of calcium channel blockers combined with standard iron chelation therapy in people with transfusion-dependent beta thalassaemia on the amount of iron deposited in the myocardium, on parameters of heart function, and on the incidence of severe heart failure or arrhythmias and related morbidity and mortality. Search methods We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials databases, and the reference lists of relevant articles and reviews. Date of last search: 24 February 2018. Selection criteria We included randomised controlled trials of calcium channel blockers combined with standard chelation therapy compared with standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia. Data collection and analysis Two authors independently applied the inclusion criteria for the selection of trials. Two authors assessed the risk of bias of trials and extracted data and a third author verified these assessments. The authors used the GRADE system to assess the quality of the evidence. Main results Two randomised controlled trials (n = 74) were included in the review; there were 35 participants in the amlodipine arms and 39 in the control arms. The mean age of participants was 24.4 years with a standard deviation of 8.5 years. There was comparable participation from both genders. Overall, the risk of bias in included trials was low. The quality of the evidence ranged across outcomes from low to high, but the evidence for most outcomes was judged to be low quality. Cardiac iron assessment, as measured by heart T2*, did not significantly improve in the amlodipine groups compared to the control groups at six or 12 months (low-quality evidence). However, myocardial iron concentration decreased significantly in the amlodipine groups compared to the control groups at both six months, mean difference -0.23 mg/g (95% confidence interval -0.07 to -0.39), and 12 months, mean difference -0.25 mg/g (95% confidence interval -0.44 to -0.05) (low-quality evidence). There were no significant differences between treatment and control groups in serum ferritin (low-quality evidence), liver T2* (low-quality evidence), liver iron content (low-quality evidence) and left ventricular ejection fraction (low-quality evidence). There were no serious adverse events reported in either trial; however, one trial (n = 59) reported mild adverse events, with no statistically significant difference between groups (low-quality evidence). Authors' conclusions The available evidence does not clearly suggest that the use of calcium channel blockers is associated with a reduction in myocardial iron in people with transfusion-dependent beta thalassaemia, although a potential for this was seen. There is a need for more long-term, multicentre trials to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should be designed to compare commonly used iron chelation drugs with the addition of calcium channel blockers to investigate the potential interplay of these treatments. In addition, the role of baseline myocardial iron content in affecting the response to calcium channel blockers should be investigated. An analysis of the cost-effectiveness of the treatment is also required. more...
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- 2018
13. Patient with Proteus syndrome and paratesticular ovarian-type papillary serous carcinoma
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Arthur B. Meyers, Chi K. Nguyen, Angela Nguyen, Roger Berkow, Alina Sadaf, and Mark A. Wehry
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,business.industry ,Hematology ,030105 genetics & heredity ,medicine.disease ,Proteus syndrome ,Papillary Serous Carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,medicine ,business ,Cystadenocarcinoma - Published
- 2018
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14. A systematic review of interventions for reducing parental vaccine refusal and vaccine hesitancy
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Saad B. Omer, Jason M. Glanz, Jennifer L. Richards, Alina Sadaf, and Daniel A. Salmon
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Parents ,medicine.medical_specialty ,Pediatrics ,Health Knowledge, Attitudes, Practice ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Public health ,Vaccination ,Public Health, Environmental and Occupational Health ,Psychological intervention ,Intervention studies ,Treatment Refusal ,Infectious Diseases ,Intervention (counseling) ,Family medicine ,Vaccine refusal ,Molecular Medicine ,Medicine ,Humans ,Limited evidence ,business - Abstract
Unvaccinated individuals pose a public health threat to communities. Research has identified many factors associated with parental vaccine refusal and hesitancy toward childhood and adolescent immunizations. However, data on the effectiveness of interventions to address parental refusal are limited. We conducted a systematic review of four online databases to identify interventional studies. We used criteria recommended by the WHO's Strategic Advisory Group of Experts on immunization (SAGE) for the quality assessment of studies. Intervention categories and outcomes were evaluated for each body of evidence and confidence in overall estimates of effect was determined. There is limited evidence to guide implementation of effective strategies to deal with the emerging threat of parental vaccine refusal. There is a need for appropriately designed, executed and evaluated intervention studies to address this gap in knowledge. more...
- Published
- 2013
15. Effect of L-type calcium channel blocker (amlodipine) on myocardial iron deposition in patients with thalassaemia with moderate-to-severe myocardial iron deposition: protocol for a randomised, controlled trial
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Alina Sadaf, Zehra Fadoo, Farheen Quadri, Amarah Shakoor, Mohammad Khurshid, Maaman Zahoor, Babar Hasan, Zaffar Sajjad, Steven D. Colan, Arjumand Rizvi, Najveen Alvi, and Fateh Ali Tipoo
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Male ,Time Factors ,Thalassemia ,Cardiomyopathy ,Calcium channel blocker ,Severity of Illness Index ,law.invention ,Electrocardiography ,Randomized controlled trial ,law ,Protocol ,Prospective Studies ,Child ,Prospective cohort study ,Chelating Agents ,Heart ,General Medicine ,Calcium Channel Blockers ,Treatment Outcome ,Drug Therapy, Combination ,Female ,Cardiomyopathies ,medicine.drug ,medicine.medical_specialty ,Iron Overload ,Adolescent ,Calcium Channels, L-Type ,medicine.drug_class ,Iron ,Magnetic Resonance Imaging, Cine ,Young Adult ,Pharmacotherapy ,Internal medicine ,Severity of illness ,medicine ,Humans ,Amlodipine ,Dose-Response Relationship, Drug ,business.industry ,Myocardium ,Paediatrics ,Stroke Volume ,medicine.disease ,Surgery ,business ,Follow-Up Studies - Abstract
Introduction Sideroblastic cardiomyopathy secondary to repeated blood transfusions is a feared complication in thalassaemia. Control of myocardial iron is thus becoming the cornerstone of thalassaemia management. Recent evidence suggests a role for L-type Ca2+ channels in mediating iron uptake by the heart. Blocking the cellular iron uptake through these channels may add to the benefit of therapy to standard chelation in reducing myocardial iron. We aim to determine the efficacy of amlodipine (a calcium channel blocker) as an adjunct to standard aggressive chelation in retarding myocardial iron deposition in thalassaemics with or without cardiomyopathy. Outcomes The primary outcome is to compare the efficacy of amlodipine+chelation (intervention) versus standard chelation (control) in retarding myocardial iron deposition. Secondary outcomes include the effect of amlodipine therapy on systolic and diastolic function, strain and strain rate and liver iron content. Methods and analysis This is a single-centre, parallel-group, prospective randomised control trial. Twenty patients will be randomised in a 1:1 allocation ratio into the intervention and control arms. In addition to conventional echocardiography, MRI T2* values for assessment of cardiac and liver iron load will be obtained at baseline and at 6 and 12 months. Cardiac T2* will be reported as the geometric mean and per cent coefficient of variation, and an increase in cardiac T2* values from baseline will be used as an end point to compare the efficacy of therapy. A p Value of more...
- Published
- 2014
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