Corrigendum: Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency.

[This corrects the article DOI: 10.3389/fimmu.2022.1075527.].

Hereditary factor X deficiency in America survey: impact on quality of life and burden of disease in patients and caregivers.

Hereditary factor X deficiency (HFXD) is a rare bleeding disorder causing delayed haemostasis and potentially life-threatening bleeds. Patient/caregiver burden and diagnosis path have not been well characterized. THE AIM OF THIS STUDY WAS TO: describe the diagnosis path, disease burden, and HFXD impact on quality of life (QoL) in patients and caregivers.This was a prospective, cross-sectional, web-based survey of patients with HFXD and caregivers addressing the patient/caregiver experience, QoL, humanistic and unmet needs.Thirty patients and 38 caregivers completed the survey with mean ages 24.7 and 44.6 years, respectively. Mean age at diagnosis was 4.1 years. The diagnostic process was somewhat/very difficult for 23% of patients and 26% of caregivers. Approximately half (53%) received single factor replacement (SFR) as prophylaxis or on-demand. Most patients (71%) reported regular prophylaxis treatment. Over one-fourth (27%) reported treatment with fresh frozen plasma. Bleeding episodes were less common in patients using SFR versus non-SFR: three bleeds or fewer were reported by 92% SFR and 75% non-SFR patients. HFXD patients reported low well being in work/school/social activities with mean HFXD-adapted Hemophilia Well being Index. Patient symptoms negatively impacted caregiver burden with a mean HFXD-adapted Hemophilia Caregiver Index (±SD) of 15.9 (4.6), but also unexpectedly had a positive impact on self-worth and inner strength.To our knowledge, this is the first study to assess patient and caregiver burden of HFXD and impact on QoL. Improvements in symptom recognition, prompt diagnosis, and adherence to expert recommendations for treatment could improve QoL and decrease burden on HFXD patients and caregivers.

Global epidemiology of factor XI deficiency: A targeted review of the literature and foundation reports.

INTRODUCTION: Hereditary factor XI (FXI) deficiency is a rare coagulation disorder that may result in excessive bleeding requiring intervention to restore haemostasis. AIM: The aim of this review was to report the current knowledge of the worldwide incidence and prevalence of FXI deficiency. METHODS: A targeted PubMed search using terms related to FXI deficiency was conducted to identify studies published from April 2002 through April 2022. A manual search supplemented the electronic search. Studies were eligible for data abstraction if they reported population-based incidence proportions/rates or prevalence proportions for FXI deficiency. RESULTS: The electronic and manual searches returned 253 publications. After applying exclusion criteria, seven publications were included in the analysis, including a global report from the World Federation of Haemophilia (WFH). Six publications provided information on the prevalence of FXI deficiency that included 74 countries and regions. The estimated prevalence of FXI in the WFH report ranged from 0/100,000 in several countries to 55.85/100,000 individuals in the United Kingdom. Prevalence estimates in the PubMed findings ranged from .1 to 246.2/1,000,000 inhabitants with varying methods of case identification and time periods of analysis. One study estimated the incidence of FXI deficiency in Yecla, Spain at 2% of blood donors and .09% of hospital inpatients/outpatients with activated partial thromboplastin time (aPTT) tests. CONCLUSION: FXI deficiency is rare across the world, but additional steps could be taken to improve incidence and prevalence estimation, for example, development of a consistent FXI deficiency definition and incorporating genetic testing into a clinical routine to better identify and characterise cases.

Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency.

Introduction: Headache and migraine adverse events are common concerns in the administration of intravenous immune globulins (IVIG). Trials of IVIG for primary immunodeficiency (PI) are typically small and have reported headache and migraine data inconsistently. Methods: We analyzed headache and migraine in pooled data from three pivotal trials of Gammaplex® 5% and 10% in PI (NCT00278954 from January 18, 2006; NCT01289847 from January 27, 2011; NCT01963143 from September 13, 2013). The trials were pooled in a retrospective analysis that included two 12-month open-label non-comparative trials of the 5% IVIG product and one 6-month open-label crossover bioequivalence trial comparing the 5% IVIG and 10% IVIG products. The population included adult and pediatric patients, who received IVIG infusions of 300-800 mg/kg/infusion every 21 or 28 days using a 15-minute rate escalation protocol. Results: In total, 1482 infusions were administered to 123 patients, with 94.6% of infusions achieving the maximum infusion rate. At least one product-related headache was reported in 6.1% (90/1482) of infusions. At least one product-related migraine was reported in 0.5% (7/1482) of infusions. Headache rates were higher for adults vs pediatric patients, females vs males, and 21-day vs 28-day dosing schedules, but were similar for the 5% and 10% IVIG products. Most headaches and migraines occurred during or within 72 hours of the infusion. Rates decreased after the first few infusions. Discussion: Patients receiving this IVIG product on a 15-minute rate escalation protocol had low rates of headache and migraine for both the 5% and 10% formulations.

Delay in the progression of low-risk prostate cancer: rationale and design of the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial.

PURPOSE: Men with prostate cancer may live as long as men their age without prostate cancer. Those with low-risk disease may benefit from expectant management, which actively monitors disease progression. Dutasteride, a dual 5alpha-reductase inhibitor (5ARI), may delay prostate cancer progression or extend the time to initiation of more aggressive therapy. MATERIALS AND METHODS: The Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial will evaluate whether dutasteride decreases time to prostate cancer progression. Three hundred candidates for expectant management with biopsy-proven, low-risk, localized prostate cancer will receive dutasteride 0.5 mg/day or placebo for 3 years. Eligible men are between 50 and 80 years of age, have clinical stage T1c-T2a prostate cancer, a Gleason score of less than or equal to 6, and serum prostate-specific antigen (PSA) less than or equal to 10 ng/mL. Entry biopsy of at least 10 cores had to be performed within 6 months of screening and will be repeated at 1.5 and 3 years. Men will complete questionnaires to measure symptoms, quality of life (QOL), and anxiety. Because PSA is an important monitoring tool in expectant management that may impact patients' comfort levels, actual PSA values will be provided to physicians and subjects. Time-to-disease progression (primary therapy for prostate cancer or pathologic progression), positive cores, change in Gleason score, and QOL assessments will be compared between groups. RESULTS: The trial completed recruitment of 302 subjects in March 2007. The study will be completed in 2010. CONCLUSIONS: The REDEEM study will evaluate the potential for dutasteride to delay disease progression in men with low-risk, localized prostate cancer. This study will better define which patients with prostate cancer can be managed with less invasive and potentially less debilitating therapy.

The effect of dutasteride on the peripheral and transition zones of the prostate and the value of the transition zone index in predicting treatment response.

PURPOSE: We determined the effects of dutasteride on transition and peripheral zone volume, and the clinical value of the transition zone index in men with benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 2,802 men 50 years or older with diagnosed benign prostatic hyperplasia, American Urological Association symptom index score 12 or greater, total prostate volume 30 cc or greater, prostate specific antigen 1.5 ng/ml or greater and 10 ng/ml or less, and peak urinary flow rate 15 ml per second or less were randomized to receive 0.5 mg dutasteride daily or placebo for 2 years. Total prostate and transition zone volume was measured with transrectal ultrasound at baseline and 4 times during the 2-year period. Peripheral zone volume (total prostate volume minus transition zone volume) and the transition zone index (transition zone volume/total prostate volume) were calculated. Patients were stratified into tertiles according to baseline total prostate and transition zone volume, and the transition zone index. RESULTS: At 24 months dutasteride significantly decreased total prostate volume from baseline (p <0.0001). There were similar decreases in transition and peripheral zone volume (approximately 25%). In men receiving placebo high baseline total prostate and transition zone volume, and transition zone index were associated with poor 2-year outcomes, ie a low peak urinary flow rate, high American Urological Association symptom index scores, and an increased frequency of acute urinary retention and benign prostatic hyperplasia related surgery. Improvements in outcomes with dutasteride vs placebo were greatest in men with the highest baseline total prostate and transition zone volume, and transition zone index. In men with low (30 to less than 42 cc) and intermediate (42 to less than 58 cc) baseline total prostate volume the benefits of dutasteride therapy were only significant in the intermediate (0.4 to less than 0.55) and high (0.55 to less than 1.0) transition zone index tertiles. CONCLUSIONS: Total prostate and transition zone volume, and the transition zone index are directly related to benign prostatic hyperplasia progression. The transition zone index may add value to transition zone volume alone for predicting outcomes. Dutasteride decreased transition and peripheral zone volume equally, supporting a known therapeutic role in benign prostatic hyperplasia and a possible preventive role in prostate cancer.

Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia.

OBJECTIVES: To assess the long-term safety and efficacy of dutasteride, a dual type 1 and type 2 5-alpha-reductase inhibitor, in the treatment of symptomatic benign prostatic hyperplasia and associated lower urinary tract symptoms. METHODS: Data from two Phase IIIa multicenter, randomized, placebo-controlled trials of 2-year duration plus a 2-year open-label extension were pooled and analyzed. The entry criteria included age 50 years old or older, clinical diagnosis of benign prostatic hyperplasia, prostate volume of 30 cm3 or greater, American Urological Association symptom score of 12 or greater, peak urinary flow rate of 15 mL/s or less, and prostate-specific antigen level of 1.5 ng/mL or greater but less than 10 ng/mL. RESULTS: A total of 2802 men were randomized into the double-blind phase of the two studies with 1908 patients (68%) completing the study. Of these, 1570 subjects were enrolled in the open-label phase, and 569 subjects received dutasteride for 48 months. Changes at the 48-month visit for dutasteride/dutasteride-treated subjects included improvement in prostate volume (-26.2%), American Urological Association Symptom Index (-6.1 points), and peak urinary flow rate (+2.8 mL/s). Changes for the placebo/dutasteride group included prostate volume (-20.7%), American Urological Association Symptom Index (-5.3 points), and peak urinary flow rate (+1.8 mL/s). Acute urinary retention and surgery occurred in a small percentage of subjects (less than 2% and less than 1%) in the open-label extension phase. Dutasteride was well tolerated with no statistically significant increase in drug-related adverse events during the open-label extension and no adverse laboratory trends. CONCLUSIONS: Dual inhibition of 5-alpha-reductase with dutasteride provided sustained efficacy in subjects with symptomatic benign prostatic hyperplasia treated for 48 months. Near-complete, long-term suppression of dihydrotestosterone (93% at 48 months) with dutasteride did not lead to an increase in adverse events compared with that reported in the 2-year period.

Disposition and intracellular activity of azithromycin in human THP-1 acute monocytes.

Uptake of [14C]-azithromycin into THP-1 human monocytes was determined at pH 7.4, 6.8 or 5.5 over 4-log antibiotic concentrations for 24 h under a number of conditions. Stimulation of cells was with bacteria, latex beads, lipopolysaccharide (LPS), or zymogen A. Subcellular organelle disposition was determined after isolation by ultracentrifugation or sucrose gradients. Hydrolytic enzyme activities and mediators of intracellular inflammation (IL-1, IL-6, IL-8, and TNFalpha) were assessed. Azithromycin uptake into human THP-1 monocytes was initially linear achieving approximately 2% of the extracellular concentration. At pH 7.4, uptake was both passive- and carrier-mediated, but as the pH became more acidic, the uptake was exclusively passive. The intracellular concentration was not pH-dependent over 24 h. Uptake was dependent upon temperature but not the presence of foetal calf serum. Intracellular disposition in zymogen A-stimulated and unstimulated cells was throughout all compartments of the cell, but was higher in the nucleus and cell sap. Phagosomes of stimulated cells contained higher level of the antibiotic. Efflux from THP-1 monocytes was complete between 3 and 4 h. After 1 h treatment with zymogen A, THP-1 monocytes demonstrated an increase in intracellular acidity, protein kinase C, SOD and NAG activities, and NO, H(2)O(2), TNFalpha and IL-1 release over the 1st h. After 2-4 h the pH became alkaline, activities of NADPH reductase, NAG and cathepsin were reduced, and the release of NO, H(2)O(2), TNFalpha and IL-6 were suppressed. Protein synthesis and killing of the bacteria was evident in bacteria kept in monocyte-free medium and those phagocytized by the THP-1 monocytes moderately at 2 h, but more significantly at 24 h. The early killing of the bacteria appears to be a cidal mechanism whereas later, a standard bacteriostatic mechanism was evident. Nevertheless, suppression of these chemical mediators and hydrolytic enzyme activities would reduce the infection and the spread to adjacent areas.