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BACKGROUND AND AIMS: Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. APPROACH AND RESULTS: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies.
- MeSH
- Biomarkers urine MeSH
- Adult MeSH
- Porphyrias, Hepatic drug therapy physiopathology urine MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Porphobilinogen Synthase deficiency urine MeSH
- Prospective Studies MeSH
- Recurrence MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
INTRODUCTION: Currently, limited data are available on long-term use of dupilumab to treat atopic dermatitis (AD) in a multinational real-world setting. The aim of this analysis was to report the interim 1-year data for patients with AD enrolled in the GLOBOSTAD registry, including treatment patterns, dupilumab effectiveness and safety, and healthcare burden. METHODS: GLOBOSTAD is an ongoing, 5-year, multinational, prospective, observational study of adult/adolescent (aged ≥ 12 years at baseline) patients with AD who initiated dupilumab in real-world settings according to their local country-specific prescribing guidelines. Outcomes were evaluated at baseline and at 3, 6 and 12 months and included Eczema Area and Severity Index (EASI) total score, SCORing Atopic Dermatitis (SCORAD) total score, percent body surface area (BSA) affected, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI) total score for adults or Children's Dermatology Life Quality Index (CDLQI) total score for adolescents and pruritus Numeric Rating Scale (NRS) total score. RESULTS: At the interim 1-year cut-off (March 2023), 955 patients were enrolled in GLOBOSTAD, and follow-up data were obtained from 903 patients. After dupilumab initiation, mean improvements in effectiveness outcome measures from baseline to month 3 were EASI from 25.1 to 6.1, SCORAD 59.3 to 25.3, POEM 19.7 to 8.7, DLQI 13.7 to 5.3, CDLQI 12.2 to 2.7 and pruritus NRS 6.3 to 2.5, with each measure exceeding the minimal clinically important difference. These positive changes in effectiveness outcomes were maintained or further improved through 12 months since treatment initiation. AD-related hospitalizations and emergency room or urgent care facility visits decreased from 11.1% to 1.7% from baseline to month 12. CONCLUSIONS: In a multinational real-world setting, dupilumab demonstrated rapid, robust and sustained effectiveness in patients with moderate-to-severe AD across multiple disease domains, including AD signs, symptoms, quality of life and emergency/urgent care visits. Safety was consistent with the known dupilumab safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03992417.
- MeSH
- Dermatitis, Atopic * drug therapy MeSH
- Child MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized * therapeutic use MeSH
- Quality of Life * MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Prospective Studies MeSH
- Registries MeSH
- Severity of Illness Index * MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
PURPOSE: We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials. PATIENTS AND METHODS: This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome. RESULTS: With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction. CONCLUSION: MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis genetics mortality therapy MeSH
- Time Factors MeSH
- Diploidy * MeSH
- Child MeSH
- Progression-Free Survival MeSH
- Transplantation, Homologous MeSH
- Clinical Trials as Topic MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Child, Preschool MeSH
- Antineoplastic Agents adverse effects therapeutic use MeSH
- Retrospective Studies MeSH
- Neoplasm, Residual MeSH
- Hematopoietic Stem Cell Transplantation * adverse effects mortality MeSH
- Age Factors MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Comparative Study MeSH
Background Guidelines on the management of orally anticoagulated patients are continuously evolving, leading to an increased need for pharmacists to be fully integrated in care provision. Objective To identify self-reported gaps in confidence among practicing pharmacists in the area of anticoagulation. Setting Pharmacists in different work settings in different countries. Method Cross-sectional international survey from October 2015 till November 2016 among pharmacists working in different settings to assess their level of confidence when delivering anticoagulants as well as to identify possible educational needs regarding this medication class. Validation of the survey was ensured. Results Responses from 4212 pharmacists originating from 18 countries were obtained. Pharmacists' level of confidence was significantly higher (p < 0.001) when advising patients on vitamin K antagonists (VKAs) versus non-vitamin K antagonists (NOACs). In general, hospital pharmacists displayed higher confidence levels compared to community pharmacists when advising patients on anticoagulation (p < 0.001). Two distinct patterns of confidence levels emerged relating to basic and advanced pharmaceutical care. Confidence levels when providing advanced pharmaceutical care were significantly higher for Oceania and lower for South America (p < 0.005). Conclusions Pharmacists felt more confident in supporting patients receiving VKAs compared to the more recently introduced NOACs. With the increasing use of NOACs and the risks pertaining to anticoagulation therapy, it is essential to invest in education for pharmacists to address their knowledge gaps enabling them to confidently support patients receiving oral anticoagulants.
- MeSH
- Anticoagulants therapeutic use MeSH
- Adult MeSH
- Pharmacists psychology MeSH
- Internationality MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Pharmacy Service, Hospital statistics & numerical data MeSH
- Cross-Sectional Studies MeSH
- Community Pharmacy Services statistics & numerical data MeSH
- Health Knowledge, Attitudes, Practice * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
