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Advances in therapies for hemophilia have led to an increased life expectancy for people with hemophilia. Limited data exist on the aging population of people with hemophilia who face additional challenges of age-related comorbidities. Efmoroctocog alfa (a recombinant factor VIII Fc fusion protein [herein referred to as rFVIIIFc]) and eftrenonacog alfa (a recombinant factor IX Fc fusion protein [rFIXFc]) are extended half-life factor replacements for hemophilia A and B, respectively, with demonstrated long-term safety and efficacy. The objective of this post hoc analysis was to describe long-term outcomes in participants 50+ years of age treated with rFVIIIFc or rFIXFc in pivotal Phase 3 trials and their extension studies: A-LONG (NCT01181128; n=21) and ASPIRE (NCT01454739; n=20 [95%]); B-LONG (NCT01027364; n=26) and B-YOND (NCT01425723; n=16 [62%]). Approximately half of participants (48%) with hemophilia A and 62% of participants with hemophilia B had a comorbidity at baseline. More than half of the participants were taking 1+ concomitant medication at baseline, with arthropathy and joint pain reported as the most common indications. Prophylaxis with rFVIIIFc or rFIXFc in individuals 50+ years of age with hemophilia A or B, respectively, resulted in low annualized bleed rates and improvements in joint health. Positive impacts on health-related quality of life were observed in individuals on either rFVIIIFc or rFIXFc prophylaxis. The results for the older subgroups were consistent with the overall study populations, demonstrating that prophylaxis with rFVIIIFc or rFIXFc provides long-term clinical benefits irrespective of age and presence of target joints in patients with severe hemophilia.
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Immune thrombocytopenia (ITP) is an autoimmune disease typically associated with severely depleted platelet counts. However, additional symptoms (e.g. increased fatigue and memory/concentration difficulties) can profoundly impact patients' quality of life. The nature and severity of cognitive impairment in ITP, and potential association with patient/disease characteristics were evaluated in 49 adults with relapsed/refractory ITP. The Cogstate Brief Battery quantitatively assessed psychomotor function (DET), attention (IDN), visual learning (OCL) and working memory (ONB) individually, as well as DET/IDN and OCL/ONB composites. Clinically important cognitive impairment (defined as z-score ≤ -1) for ≥2 individual tests was observed in 29 patients (59%). Impairment was highest for IDN (67% of patients), followed by DET (53%), ONB (39%) and OCL (16%). A higher magnitude of impairment was observed for the DET/IDN composite (mean z-score -1.54; 95% CI, -1.94 to -1.13) than OCL/ONB (mean z-score -0.21; 95% CI, -0.49 to 0.07). The severity of cognitive impairment was comparable to mild traumatic brain injury and associated with increasing age and fatigue but unrelated to platelet count or corticosteroid use. Overall, these results warrant a clinical need to further consider the potential of cognitive dysfunction in assessing ITP patients.
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Disfunção Cognitiva , Púrpura Trombocitopênica Idiopática , Humanos , Púrpura Trombocitopênica Idiopática/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Disfunção Cognitiva/etiologia , Adulto , Idoso , Doença Crônica , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: High-voltage pulses can cause hemolysis. OBJECTIVES: The authors evaluated the occurrence of hemoglobinuria after pulsed-field ablation (PFA) and its impact on renal function in patients with atrial fibrillation (AF). METHODS: A consecutive series of patients with AF undergoing PFA were included in this analysis. The initial patients who did not receive postablation hydration immediately after the procedure were classified as group 1 (n = 28), and the rest of the study patients who received planned fluid infusion (0.9% sodium chloride ≥2 L) after the procedure were categorized as group 2 (n = 75). RESULTS: Of the 28 patients in group 1, 21 (75%) experienced hemoglobinuria during the 24 hours after catheter ablation. The mean postablation serum creatinine (S-Cr) was significantly higher than the baseline value in those 21 patients (1.46 ± 0.28 mg/dL vs 0.86 ± 0.24 mg/dL, P < 0.001). Of those 21 patients, 4 (19%) had S-Cr. >2.5 mg/dL (mean: 2.95 ± 0.21 mg/dL). The mean number of PF applications was significantly higher in those 4 patients than in the other 17 patients experiencing hemoglobinuria (94.63 ± 3.20 vs 46.75 ± 9.10, P < 0.001). In group 2 patients, no significant changes in S-Cr were noted. The group 2 patients received significantly higher amounts of fluid infusion after catheter ablation than did those in group 1 (2,082.50 ± 258.08 mL vs 494.01 ± 71.65 mL, P < 0.001). In multivariable analysis, both hydration (R2 = 0.63, P < 0.01) and number of PFA applications (R2 = 0.33, P < 0.01) were independent predictors of postprocedure acute kidney injury. CONCLUSIONS: On the basis of our findings, both the number of PFA applications and postablation hydration were independent predictors of renal insult that could be prevented using planned fluid infusion immediately after the procedure.
Assuntos
Injúria Renal Aguda , Fibrilação Atrial , Ablação por Cateter , Hemoglobinúria , Humanos , Fibrilação Atrial/cirurgia , Masculino , Feminino , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Pessoa de Meia-Idade , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/etiologia , Idoso , Hemoglobinúria/etiologia , Hemoglobinúria/prevenção & controle , Creatinina/sangue , Estudos Retrospectivos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Hidratação/métodosRESUMO
Patients with cold agglutinin disease (CAD) are more vulnerable to infectious agents, thus the COVID-19 pandemic has posed a particular risk to this population. Sutimlimab Phase 3 studies CARDINAL and CADENZA spanned the period before and during the pandemic; investigators were advised to vaccinate enrolled patients without stopping treatment. Of 61 completers from both studies, 47 received ≥1 dose of a COVID-19 vaccine. In the immunogenicity analysis (n = 27) all patients developed an immune response post-COVID-19 vaccination, with detectable immunoglobulin G anti-spike antibodies. Analysis of six patients with booster vaccinations demonstrated increased immune responses pre- to post-booster. COVID-19 vaccines were well tolerated in patients with CAD receiving sutimlimab treatment, and no signs of hemolytic exacerbations were observed post-vaccination.
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Anemia Hemolítica Autoimune , Anticorpos Monoclonais Humanizados , COVID-19 , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Pandemias , Anticorpos AntiviraisRESUMO
Heart failure is a significant cause of morbidity and mortality worldwide. Despite advancements in guideline-directed medical therapy and improvements in device-based therapies, patients with advanced heart failure have high rates of mortality regardless of ejection fraction. For patients with reduced ejection fraction who meet criteria, cardiac resynchronization therapy or implantable cardiac defibrillators are options available to improve outcomes. However, not all heart failure patients meet those criteria. Cardiac contractility modulation is an innovative therapy that serves to improve functional outcomes and quality of life, while also modifying pathologic gene expression and preventing further remodeling. In this article, we aim to discuss the major clinical trials investigating cardiac contractility modulation as a suitable therapy for patients with advanced heart failure.
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Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Humanos , Qualidade de Vida , Volume Sistólico , Resultado do TratamentoRESUMO
The frequencies of 6 different facultative pathogenic bacteria of the ESKAPE group (priority list WHO) and a total of 14 antibiotic resistance genes (ARGs) with different priorities for human medicine were quantified in wastewaters of poultry and pig slaughterhouses using molecular biological approaches. Raw sewage from poultry and pig slaughterhouses was found to be contaminated not only with facultative pathogenic bacteria but also with various categories of clinically relevant ARGs, including ARGs against the reserve antibiotics group. The concentration of the different gene targets decreased after on-site conventional biological or advanced oxidative wastewater treatments, but was not eliminated. Hence, the antimicrobial BlueLight (aBL) in combination with a porphyrin photo-sensitizer was studied with ESKAPE bacteria and real slaughterhouse wastewaters. The applied broad LED-based blue light (420-480 nm) resulted in groups of sensitive, intermediate, and non-sensitive ESKAPE bacteria. The killing effect of aBL was increased in the non-sensitive bacteria Klebsiella pneumoniae and Enterococcus faecium due to the addition of porphyrins in concentrations of 10-6 M. Diluted slaughterhouse raw wastewater was treated with broad spectrum aBL and in combination with porphyrin. Here, the presence of the photo-sensitizer enhanced the aBL biocidal impact.
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Porfirinas , Águas Residuárias , Animais , Suínos , Humanos , Matadouros , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Antibacterianos/farmacologia , Genes Bacterianos , TecnologiaRESUMO
INTRODUCTION: Although work to date in cystic fibrosis (CF) has elucidated frequencies and characteristics of adverse events, the accuracy of attribution of relatedness to study drug by investigators has not been assessed. We aimed to determine whether there was an association of attribution by group allocation in CF clinical trials. METHODS: We conducted a secondary analysis from 4 CF trials of all persons who experienced an AE. Our primary outcome was the odds of an AE related to active study drug and predictor of interest was the treatment allocation. We constructed a multivariable generalized estimating equation model allowing for repeated measures. RESULTS: A total of 785 subjects (47.5% female, mean age 12 years) had 11,974 AEs, of which 430 were serious. AE attribution was greater with receipt of active study drug as compared to placebo but did not reach statistical significance (OR 1.38, 95% CI 0.98-1.82). Significantly associated factors included female sex (OR 0.58, 95% 0.39-0.87), age (OR 1.24, 95% CI 1.06-1.46) and baseline lung function (per 10%, OR 1.16, 95% CI 1.05-1.28). CONCLUSION: In our large study, there was a non-significant but greater odds of AE attribution (a key element of clinical trial reporting) to active study drug based on assigned treatment to study drug or control which suggests that there is a trend in physicians to attribute blinded safety data to the active drug. Interestingly, females were less likely to have AE attribution to study drug and warrants further work in development and validation of monitoring guidelines and processes.
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Fibrose Cística , Humanos , Feminino , Criança , Masculino , Fibrose Cística/tratamento farmacológico , Fibrose Cística/epidemiologia , Viés Implícito , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de PesquisaRESUMO
In this work, an effective approach based on a nonlinear output frequency response function (NOFRF) and improved convolution neural network is proposed for analog circuit fault diagnosis. First, the NOFRF spectra, rather than the output of the system, are adopted as the fault information of the analog circuit. Furthermore, to further improve the accuracy and efficiency of analog circuit fault diagnosis, the batch normalization layer and the convolutional block attention module (CBAM) are introduced into the convolution neural network (CNN) to propose a CBAM-CNN, which can automatically extract the fault features from NOFRF spectra, to realize the accurate diagnosis of the analog circuit. The fault diagnosis experiments are carried out on the simulated circuit of Sallen-Key. The results demonstrate that the proposed method can not only improve the accuracy of analog circuit fault diagnosis, but also has strong anti-noise ability.
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BACKGROUND: Hepatitis C is a diverse illness that causes significant death and morbidity. The hepatitis C virus infects hundreds of millions of individuals globally (HCV). More than 80% of those infected develop chronic infection; the remaining 10-20% recovers spontaneously through natural immunity. Acute hepatitis is only icteric in 20% of individuals and is seldom severe. METHODS: A pilot study was conducted at INOR hospital Abbottabad. Eleven hepatitis C positive and 10 hepatitis C negative participants were included in the study. RESULTS: A significant difference correlation was found between viral load and SWE quantification for fibrosis stage in Kilo-Pascal, r=0.904 (p-value=0.000
Assuntos
Hepatite C
, Humanos
, Projetos Piloto
, Carga Viral
, Hepacivirus
, Fibrose
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BACKGROUND: Mesenchymal stem cells are of particular interest in cystic fibrosis (CF) as a potential therapeutic. Data from pre-clinical studies suggest that allogeneic bone marrow-derived human mesenchymal stem cells (hMSCs) may provide a new therapeutic treatment for CF lung disease by attenuating pulmonary inflammation while decreasing bacterial growth and enhancing antibiotic efficacy. METHODS: Fifteen adults with CF were enrolled in a phase 1 dose-escalation trial of a single intravenous infusion of hMSCs derived from bone marrow aspirates obtained from a single pre-clinically validated healthy volunteer donor. The study employed a 3+3 dose escalation design with subjects receiving a single, intravenous dose of either 1×106, 3×106, or 5×106 hMSCs/kg. Subjects were monitored inpatient for 24 hours and by outpatient visits and telephone calls for 12 months after the infusion. Safety and tolerability were evaluated by monitoring symptoms, patient reported outcome questionnaires, adverse events (AEs), physical exam findings, spirometry, and analyses of safety laboratories. Preliminary evidence for potential efficacy using inflammatory markers in the blood and sputum were also evaluated. RESULTS: No dose-limiting toxicities, deaths or life-threatening adverse events were observed. Most AEs and serious adverse events (SAEs) were consistent with underlying CF. Vital signs, physical exam findings, spirometry and safety laboratory results showed no significant change from baseline. No trends over time were seen in serum or sputum inflammatory markers nor with clinical spirometry. CONCLUSION: Allogeneic hMSC intravenous infusions were safe and well-tolerated in this phase 1 study and warrant additional clinical testing as a potential therapeutic for CF lung disease.
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Fibrose Cística , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Humanos , Adulto , Fibrose Cística/terapia , Fibrose Cística/tratamento farmacológico , Administração Intravenosa , EspirometriaRESUMO
BACKGROUND AND AIMS: People with cystic fibrosis (PwCF) suffer from gastrointestinal (GI) symptoms affecting their quality of life (QOL). Despite the relevance of GI symptoms to the overall health of PwCF, a paucity of studies only have comprehensively assessed the prevalence, severity and QOL of GI symptoms in both children and adults with Cystic Fibrosis (CF). METHODS: Eligible participants ≥2 years of age across 26 US CF centers were followed for 4 weeks. Three validated GI electronic patient-reported outcome measures (ePROMs) with a recall period of 2 weeks and a stool-specific questionnaire were administered weekly over four weeks. Total and domain scores of ePROMs were evaluated overall and in subgroups using linear mixed-effect models. RESULTS: Of 402 enrolled, 58% were ≥ 18 years of age (52% male). The mean (SD) of the total score for PAC-SYM was 0.52 (0.55), for PAGI-SYM was 0.63 (0.67), and for PAC-QOL was 0.67 (0.55). For specific ePROM questions, prevalence of moderate to very severe symptoms were as follows: straining (20.3%), fullness (18.3%), incomplete bowel movements (17.1%), bloating (16.4%), distension (16.4%), abdominal pain (upper-5.1%, lower-7.5%). Comparing participants ≥18 versus <18, a higher prevalence of bloating (63.7% versus 27.3%), lower abdominal pain (39.8% vs 26.2%), stomach fullness (75.6% versus 56.2%), and abdominal distension (60.2% versus 34.9%) was found. Both age groups reported high treatment dissatisfaction as measured with PAC-QOL, mean 1.39 (95% CI: 1.30, 1.47). CONCLUSION: GI symptoms were reported in all age ranges irrespective of gender, with higher prevalence observed amongst older and female subgroups. Dissatisfaction with GI targeted treatments were reported in a large proportion of participants despite therapy, highlighting an unmet need for clinical interventions. CLINICALTRIALS: GOV: NCT03801993.
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Fibrose Cística , Gastroenteropatias , Adulto , Criança , Humanos , Masculino , Feminino , Lactente , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Qualidade de Vida , Estudos Prospectivos , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Dor Abdominal/diagnóstico , Dor Abdominal/epidemiologia , Dor Abdominal/etiologiaRESUMO
Background: Alzheimer's disease (AD) is a multifactorial neurological disease with neurofibrillary tangles and neuritic plaques as histopathological markers. Due to this, although AD is the leading cause of dementia worldwide, clinical AD dementia cannot be certainly diagnosed until neuropathological post-mortem evaluation. Coffee has been reported to have neurologically protective factors, particularly against AD, but coffee brand and type have not been taken into consideration in previous studies. We examined the discrepancies among popular commercial and instant coffees in limiting the development and progression through Aß1-40 and Aß1-42 production, and hypothesized that coffee consumption, regardless of brand or type, is beneficial for stalling the progression and development of Aß-related AD. Methods: Coffee samples from four commercial coffee brands and four instant coffees were purchased or prepared following given instructions and filtered for the study. 5, 2.5, and 1.25% concentrations of each coffee were used to treat N2a/APPswe cell lines. MTT assay was used to assess cell viability for coffee concentrations, as well as pure caffeine concentrations. Sandwich ELISA assay was used to determine Aß concentration for Aß1-40 and Aß1-42 peptides of coffee-treated cells. Results: Caffeine concentrations were significantly varied among all coffees (DC vs. MDC, PC, SB, NIN, MIN p < 0.05). There was no correlation between caffeine concentration and cell toxicity among brands and types of coffee, with no toxicity at 0.5 mg/ml caffeine and lower. Most coffees were toxic to N2a/APPswe cells at 5% (p < 0.05), but not at 2.5%. Most coffees at a 2.5% concentration reduced Aß1-40 and Aß1-42 production, with comparable results between commercial and instant coffees. Conclusion: All coffees tested have beneficial health effects for AD through lowering Aß1-40 and Aß1-42 production, with Dunkin' Donuts® medium roast coffee demonstrating the most consistent and optimal cell survival rates and Aß concentration. On the other hand, Starbucks® coffee exhibited the highest cell toxicity rates among the tested coffees.
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BACKGROUND: The COVID-19 pandemic has accelerated the transition to telehealth, including the use of home spirometry in cystic fibrosis. Evaluating the accuracy and precision of longitudinal home spirometry is a requisite for telehealth-based research. This secondary analysis of a CF study (eICE) evaluates whether there are cross-sectional or longitudinal differences between home and clinic spirometry. METHODS: Participants age ≥14 years with ppFEV1>25 were recruited from 2011-2015, issued a home spirometer, and asked to complete spirometry efforts twice per week for one year. Clinic spirometry was collected at baseline and every three months. Cross-sectional differences between clinic spirometry and the closest home spirometry measurement were analyzed. Longitudinally, we apply 5 methods to analyze the precision of home spirometry, and differences between clinic vs. home data. RESULTS: Home spirometry is estimated to be 2.0 (95% CI: 0.3, 3.5) percentage points lower than clinic spirometry cross-sectionally. Longitudinally, the estimates of 12-month change in home spirometry varied by analysis method from -2.6 to -1.0 ppFEV1/ year, with precision markedly different. However, home spirometry change estimates were qualitatively similar to the clinic results: -3.0 ppFEV1/year (95% CI: -4.1, -1.9). CONCLUSIONS: To leverage the potential cost, feasibility and convenience of home spirometry, the differences with clinic spirometry must be acknowledged. Significantly lower ppFEV1 in home devices shows that direct comparison to clinic spirometers may induce a spurious change from baseline, and additional variability in home devices impacts statistical power. The effect of coaching, setting, and equipment must be understood to use and improve home spirometry in CF.
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Fibrose Cística/fisiopatologia , Espirometria/métodos , Telemedicina/métodos , Adolescente , Adulto , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pandemias , Cooperação do Paciente , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: The Food and Drug Administration considers patient-reported outcome measures (PROMs) an essential part of clinical research studies for approval of new drugs and new indications for existing drugs. GALAXY evaluated the feasibility of electronic PROMs (ePROMS) to conduct a comprehensive evaluation of gastrointestinal (GI) symptoms in persons with cystic fibrosis (pwCF). METHODS: Three validated GI ePROMs (PAC-SYM, PAGI-SYM and PAC-QOL) were combined with a Stool-Specific questionnaire to make up the GALAXY ePROMs and administered prospectively across 26 CF centers in the United States. The ePROMs were completed at enrollment visit and then electronically at weeks 1, 2 and 4. PwCF at least 2 years and older were eligible for the study. Reminders were only provided by the mobile application during the study window. RESULTS: There were 402 participants enrolled in GALAXY. Of those, 169 (42%) were under 18 years old and 193 (48%) were female. The proportion of all follow-up weeks with at least 1 ePROM fully completed was 80%, slightly higher in those ≥18 years of age (82.5%) compared to those <18 years of age (76.5%). When assessing the completion for all 4 ePROMs, the percentage was 77.6%, also higher among those ≥18 year of age (81.5% versus 72.2% for < 18 years of age). CONCLUSION: Using ePROMs, our study demonstrated that GI symptoms can be feasibly collected with good reproducibility and with minimal involvement of research coordinator time. This mechanism of symptom collection may provide an efficient tool for future CF trials.
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Pesquisa Biomédica/métodos , Fibrose Cística , Aplicativos Móveis , Medidas de Resultados Relatados pelo Paciente , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease characterized by chronic sinopulmonary symptoms and chronic gastrointestinal symptoms that begins in infancy. Children with CF are increasingly being included in clinical trials. In order to fully evaluate the impact of new therapies in future clinical trials, an understanding of baseline adverse event (AE) rates in children with CF is needed. To address this, we determined the rates of common AEs in pediatric patients with CF who participated in two clinical trials. METHODS: We reviewed AEs for placebo recipients in the AZ0004 study and inhaled tobramycin recipients in the Early Pseudomonas Infection Control (EPIC) clinical trial. AEs were categorized based on Medical Dictionary for Regulatory Activities (MedDRA) coding classifications and pooled into common, batched AE descriptors. AE rates were estimated from negative binomial models according to age groups, severity of lung disease, and season. RESULTS: A total of 433 children had 8,266 total AEs reported, or 18.1 (95% CI 17.0, 19.2) AEs per person per year. Respiratory AEs were the most commonly reported AEs, with a rate of 7.6 events per person-year. The total SAE rate was 0.33 per person per-year. Cough was the most commonly reported respiratory AE, with 61% of subjects reporting at least one episode of cough within 4 months. The rate ratio of any AE was higher in Spring, Fall, and Winter, compared with Summer. CONCLUSIONS: AEs occur commonly in pediatric CF clinical trial participants. Season of enrollment could affect AE rates.
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Fibrose Cística/complicações , Administração por Inalação , Antibacterianos/administração & dosagem , Criança , Pré-Escolar , Fibrose Cística/tratamento farmacológico , Fibrose Cística/microbiologia , Feminino , Volume Expiratório Forçado , Humanos , Lactente , Masculino , Estações do Ano , Índice de Gravidade de Doença , Tobramicina/administração & dosagemRESUMO
BACKGROUND: Gastrointestinal (GI) involvement among persons with cystic fibrosis (CF) is highly prevalent, representing a significant source of morbidity. Persons with CF have identified GI concerns as a top research priority, yet universal clinical outcome measures capturing many of the GI symptoms experienced in CF are lacking. The GALAXY study was envisioned to address this unmet need. METHODS: The GALAXY study team partnered with Community Voice, a community of patients with CF and their caregivers, to identify the patient reported outcome measures that most accurately reflected their experience with GI symptoms in CF. We also surveyed CF care teams to identify the comfort level of various team members (providers, nurses and dieticians) in managing a variety of GI conditions. RESULTS: Members of Community Voice identified the combination of PAC-SYM, PAGI-SYM, PAC-QOL and the Bristol Stool scale with three additional symptom-specific questions as patient-reported outcome measures that comprehensively captured the CF experience with GI disease. CF care team providers reported a high level of comfort in treating GI conditions including constipation (92%), GERD (93%), and gassiness (77%), however comfort level was limited to only first-line interventions. CONCLUSION: By partnering with persons with CF as well as their caregivers and medical providers, the GALAXY study is designed to uniquely capture the prevalence and severity of GI involvement among persons with CF in a manner that reflects the CF patient experience. The results of GALAXY will inform the development of future interventional trials and serve as a reproducible and objective study endpoint.
Assuntos
Fibrose Cística/diagnóstico , Gastroenteropatias/diagnóstico , Fibrose Cística/complicações , Gastroenteropatias/etiologia , Humanos , Estudos Longitudinais , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Avaliação de SintomasRESUMO
This paper discusses an interesting case of pan plexopathy and the difficulties associated with the diagnostic processes based on patient-specific circumstances. It walks through the major differential of the etiology of the patient's particular presenting symptoms and the associated diagnostic and therapeutic process by which this particular patient was treated. In the discussion, the relevant anatomy of the brachial plexus and the surrounding structures in both the cervical and the axillary regions is discussed and key clinical pearls that became apparent throughout the diagnostic workup that was significant for a hematoma and therapeutic process aimed at providing symptomatic relief until recovery to baseline. This case study discusses the benefits, drawbacks, and financial costs of utilizing the major different imaging modalities such as CT, MRI, or Point of Care Ultrasound (POCUS). Finally, this study provides a new diagnostic algorithm for the selection of the imaging modality based on the major principles of value-based care as detailed by both the Radiological Society of North America and the European Society of Radiology.
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Rationale: The combination of lumacaftor (LUM) and ivacaftor (IVA) is an approved CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator treatment for homozygous F508del patients with CF.Objectives: To evaluate the effectiveness of LUM/IVA in children (6 yr or more) and adults (more than 18 yr) in a postapproval setting.Methods: This longitudinal cohort study, performed at 38 centers in the U.S. CF Therapeutics Development Network, enrolled homozygous F508del patients with CF ages 6 years old and older with no prior exposure to LUM/IVA. Study assessments were performed at baseline and at 1, 3, 6, and 12 months after LUM/IVA initiation.Results: A total of 193 patients initiated LUM/IVA, and 85% completed the study through 1 year. Baseline mean percent-predicted forced expiratory volume in 1 second (ppFEV1) was 85 (standard deviation, 22.4) in this cohort. No statistically significant change in ppFEV1 was observed from baseline to any of the follow-up time points, with a mean absolute change at 12 months of -0.3 (95% confidence interval [CI], -1.8 to 1.2). Body mass index improved from baseline to 12 months (mean change, 0.8 kg/m2; P < 0.001). Sweat chloride decreased from baseline to 1 month (mean change, -18.5 mmol/L; 95% CI, -20.7 to -16.3; P < 0.001), and these reductions were sustained through the study period. There were no significant changes in hospitalization rate for pulmonary exacerbations and Pseudomonas aeruginosa infection status with treatment.Conclusions: In this real-world multicenter cohort of children and adults, LUM/IVA treatment was associated with significant improvements in growth and reductions in sweat chloride without statistically significant or clinically meaningful changes in lung function, hospitalization rates, or P. aeruginosa infection.Clinical trial registered with www.clinicaltrials.gov (NCT02477319).
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Aminofenóis , Aminopiridinas , Benzodioxóis , Fibrose Cística , Quinolonas , Adolescente , Adulto , Criança , Estudos de Coortes , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Masculino , Mutação , Adulto JovemRESUMO
INTRODUCTION: Biomarkers of inflammation in blood and sputum can play a critical role in anti-inflammatory drug development in cystic fibrosis (CF). The objectives of this analysis were to examine relationships between airway and systemic measurements of inflammation, associations between inflammatory biomarkers and FEV1, differences in airway and systemic inflammation by baseline covariates, reproducibility of serum biomarkers, and to assess the effects of freezing and delayed processing on sputum analyte measurements. METHODS: We analyzed baseline and serial concentrations of inflammatory markers in blood and induced sputum collected from individuals with CF ages 10 years and older who participated in a multicenter clinical trial. RESULTS: Among circulating biomarkers, serum high sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) correlated most strongly with each other (rs = 0.85). Comparing sputum-based inflammation measurements, sputum neutrophil elastase and myeloperoxidase (MPO) were the most highly correlated (rs = 0.88). Markers most strongly correlated with ppFEV1 were serum hsCRP (rs = -0.55), SAA (rs =-0.58), and sputum neutrophil elastase (rs = -0.53). Within-subject standard deviation was consistently lower than between-subject standard deviation for all serum biomarkers. Serum calprotectin and MPO had the highest ratio of between-to-within subject variability. Freezing and delayed sputum processing were not associated with significant differences in measurements of sputum neutrophil elastase, IL-1ß, or MPO. CONCLUSIONS: Among the biomarkers analyzed, serum hsCRP and sputum neutrophil elastase are promising candidates to include in CF anti-inflammatory clinical trials to avoid redundancy, minimize variation, and serve as correlates of lung disease severity and change.