RESUMO
Sweat chloride concentration, a diagnostic feature in cystic fibrosis (CF), reflects CF transmembrane conductance regulator (CFTR) activity. CFTR modulator therapies, especially elexacaftor/tezacaftor/ivacaftor (ETI), has improved CF outcomes. We report nationwide, real-world data on sweat chloride concentration in people with CF (pwCF) with and without modulator therapies. All Danish pwCF with a minimum of one F508del allele were included. Sweat chloride measurements were stratified by genotype and modulator treatment. Differences were assessed using mixed-effects models. We included 977 sweat chloride measurements from 430 pwCF, 71% of which were F508del homozygous. Heterozygous and homozygous ETI-treated pwCF had an estimated mean sweat chloride concentration of 43 mmol/L (95% confidence interval: 39; 48) and 43 mmol/L (39; 47), respectively-48% and 59% lower than those without treatment. High variation in concentrations remained regardless of treatment status. Despite ETI treatment, 27% heterozygous and 23% homozygous pwCF had elevated concentrations (≥60 mmol/L). These real-world data confirm a substantial decrease in sweat chloride concentration during modulator treatment, especially ETI, where mean concentrations halved. However, large variation remained, including persistently high concentrations. These findings emphasize the potential of sweat chloride concentration as a treatment response biomarker and the need to explore its heterogeneity and relationship with clinical outcomes.
RESUMO
BACKGROUND: The Danish National Patient Registry (DNPR) serves as a valuable resource for scientific research. However, to ensure accurate results in cystic fibrosis (CF) studies that rely on DNPR data, a robust case-identification algorithm is essential. This study aimed to develop and validate algorithms for the reliable identification of CF patients in the DNPR. METHODS: Using the Danish Cystic Fibrosis Registry (DCFR) as a reference, accuracy measures including sensitivity and positive predictive value (PPV) for case-finding algorithms deployed in the DNPR were calculated. Algorithms were based on minimum number of hospital contacts with CF as the main diagnosis and minimum number of days between first and last contact. RESULTS: An algorithm requiring a minimum of one hospital contact with CF as the main diagnosis yielded a sensitivity of 96.1 % (95 % CI: 94.2 %; 97.4 %) and a PPV of 84.9 % (82.0 %; 87.4 %). The highest-performing algorithm required minimum 2 hospital visits and a minimum of 182 days between the first and the last contact and yielded a sensitivity of 95.9 % (95 % CI: 94.1 %; 97.2 %), PPV of 91.0 % (95 % CI: 88.6 %; 93.0 %) and a cohort entry delay of 3.2 months at the 75th percentile (95th percentile: 38.7 months). CONCLUSIONS: The DNPR captures individuals with CF with high sensitivity and is a valuable resource for CF-research. PPV was improved at a minimal cost of sensitivity by increasing requirements of minimum number of hospital contacts and days between first and last contact. Cohort entry delay increased with number of required hospital contacts.
RESUMO
BACKGROUND: Cystic Fibrosis (CF) is an inherited multiorgan disease that causes lung damage and early death. People with CF (pwCF) experience diminished exercise capacity compared to the general population. This is due to an accelerated decline in lung function resulting from recurrent lung infections, declining lung function and nutritional challenges. Since 2020 the CFTR-modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved for pwCF aged 12 and above in Denmark. Initial experiences with the medication have shown promising results, including improved lung function and disease stability. To date a limited number of studies have evaluated the impact of CFTR-modulators on exercise capacity in pwCF. OBJECTIVE: The study aims to assess the impact of one year of ETI treatment, without any further intervention, on exercise capacity measured through cardiopulmonary exercise test (CPET) in pwCF aged 12 years and above. METHODS: A Danish prospective registry cohort study including pwCF from CF-Center Copenhagen, Copenhagen University Hospital and CF-Center Aarhus, Aarhus University Hospital. Participants underwent CPET before initiating ETI and at follow up one year later. Primary outcomes were VO2 peak (ml/kg/min), secondary outcomes were VO2 peak (ml/min), VO2 peak (% pred), watt-max, HR-max and saturation at max. The difference between baseline and follow-up was assessed using a paired-sample t-test and regression analyses were applied to relevant outcomes. RESULTS: We included 229 pwCF in the analyses. An increase in oxygen uptake, VO2 peak (ml/kg/min) from baseline to follow-up was observed; 0.6, 95% CI [0.06; 1.09] p = 0.03. Moreover, significant increase was noted for all other CPET outcomes. Regression analysis showed that changes in FEV1% pred and BMI could explain some of the differences, 0.05 ml/kg/min, 95% CI [0.01, 0.1] p = 0.02 and -0.5 ml/kg/min, 95% CI [-0.8, -0.2] p = 0.002 respectively. CONCLUSION: Among Danish pwCF we found a significant, but not clinically relevant, increase in oxygen uptake, after one year of ETI treatment.
RESUMO
BACKGROUND: Improved growth in children with CF may have resulted from advances in treatment for cystic fibrosis (CF) over the past two decades, including the implementation of newborn screening in Denmark in 2016. This observational cohort study focuses on changes in early growth in Danish children with CF born between 2000 and January 2022. METHODS: Age, length/height, and weight data of children 0-5 years old were obtained from the Danish CF Cohort. Data were stratified to four birth cohorts born between 2000 and 2022. Weight-for-age (WAZ), length-for-age (LAZ), height-for-age (HAZ) and body-mass-index (BMZ) z-scores were computed using WHO growth curves. Cubic spline mixed effects models were used to evaluate growth over 5 years between birth cohorts. RESULTS: We included 255 children in the analyses. Cubic spline mixed effects models show that catch-up growth improved in birth cohorts over time, with the 2016-2022 birth cohort achieving growth reference curve values in WAZ, LAZ/HAZ and BMZ the earliest. The proportion of underweight and stunting observations among children born 2000-2004 decreased by the 2016-2022 birth cohort, while the proportion of overweight, low BMZ and high BMZ observations increased. CONCLUSION: Advances in care for young children with CF have led to improvements in growth - with the 2016-2022 birth cohort approaching potential for overweight. Nonetheless, low BMZ remains. Immediate, individualized nutrition care throughout early childhood remain crucial in mitigating malnutrition.
RESUMO
BACKGROUND: Past and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population. METHODS: This nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality. RESULTS: The Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts. CONCLUSIONS: The disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life.
RESUMO
Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre-emptive treatment of lung disease and other CF-related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high-dose combination antimicrobial therapy. Despite a high prevalence of severe CF variants, lung function has been among the best in Europe. In this review, the Danish approach to management of CF prior to the introduction of new CF modulator treatment is explained and benchmarked. Downsides to the Danish approach are discussed and include increased burden of treatment, risk of antimicrobial resistance, side-effects and costs.
Assuntos
Anti-Infecciosos , Fibrose Cística , Humanos , Fibrose Cística/complicações , Europa (Continente) , Anti-Infecciosos/uso terapêutico , DinamarcaRESUMO
BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has improved the clinical status of individuals with cystic fibrosis (CF), however, whether ETI impacts glucose tolerance remains unknown. We aimed to study the change in glycated hemoglobin (HbA1c) and CF related diabetes (CFRD) status after initiation of ETI. METHODS: We included individuals ≥12 years treated with ETI in Denmark in a longitudinal observational study. HbA1c was measured at baseline, 3, 6, 9 and 12 months after treatment initiation. Change in HbA1c was assessed in mixed models adjusted for age, sex, glucose tolerance and prior CFTR modulator treatment. In a sub-population with CFRD, we assessed the change in insulin usage, hypoglycemic events and the 30-day continuous glucose monitoring (CGM) parameters (i.e., average blood glucose, time below (≤3.9 mM) and above (>10.0 mM) normal range, and the variation in glucose) after 12 months of treatment. RESULTS: Among 321 individuals with CF, HbA1c declined by 2.1 mmol/mol [95 % confidence interval (CI): -2.6; -1.5 mmol/mol] after 3 months and by 2.3 mmol/mol [95 %CI: -2.8; -1.9 mmol/mol] after 12 months of ETI treatment. The decline was independent of glucose tolerance status at baseline. In 26 individuals with CFRD at baseline, the mean decline in HbA1c was 3.6 mmol/mol [95 %CI: -6.9; -0.4 mmol/mol] after 12 months, but we did not observe any change in insulin usage, weekly number of hypoglycemic events or CGM parameters. CONCLUSION: In the Danish CF cohort, HbA1c declined over 12 months of ETI treatment, however, among a subset with CFRD, we observed no change in insulin usage and CGM glucose levels.
Assuntos
Glicemia , Fibrose Cística , Indóis , Pirazóis , Piridinas , Pirrolidinas , Quinolonas , Humanos , Automonitorização da Glicemia , Fibrose Cística/tratamento farmacológico , Fibrose Cística/epidemiologia , Hemoglobinas Glicadas , Insulina , Hipoglicemiantes/uso terapêutico , Glucose , Dinamarca/epidemiologia , Regulador de Condutância Transmembrana em Fibrose Cística , Benzodioxóis , Mutação , Aminofenóis/uso terapêuticoRESUMO
RATIONAL: People with cystic fibrosis carrying residual function (RF) mutations are considered to have a mild disease course. This may influence caregivers and patients on how intensive the treatments should be. OBJECTIVES: Characterize disease severity of patients carrying RF mutations, using the European CF Society Patient Registry (ECFSPR) data. METHODS: Demographic, clinical characteristics, lung function and death probability of patients carrying at least one RF mutation were analyzed and compared to patients homozygous to minimal function mutations (MF). MAIN RESULTS: Of the 44,594 eligible patients (median age 19.5 years, IQR 10-29.8), 6,636 (14.6%) carried RF mutations, and 37,958 (85.1%) MF mutations. Patients carrying RF mutations were older, diagnosed at a later age, had lower sweat chloride at diagnosis and better FEV1pp at each age group. However, their FEV1pp declined with age and rates of chronic Pseudomonas aeruginosa increased with age. A significant number of patients with RF had FEV1pp similar to patients with MF at each age group. 4.5% of RF patients were treated with oxygen and 2.61% had a lung transplant. With increasing age, 26.6% of RF patients were treated with pancreatic enzymes associated with a more severe lung disease. RF patients had shortened life spans, with mortality starting around the age of 20 years. CONCLUSIONS: Patients carrying an RF mutations experience a decline of pulmonary function with age, leading to life-shortening. Standard of care therapies and augmenting CFTR function may improve their survival and quality of life.
Assuntos
Fibrose Cística , Humanos , Adulto Jovem , Adulto , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , Qualidade de Vida , Mutação , Gravidade do Paciente , Sistema de RegistrosRESUMO
BACKGROUND: Paediatric track and trigger tools (PTTTs) based on vital parameters have been implemented in hospitals worldwide to help healthcare professionals identify signs of critical illness and incipient deterioration in hospitalised children. It has been documented that nurses do not use PTTT as intended, but deviate from PTTT protocols because, in some situations, PTTT observations make little sense to them. The present study aimed to reach consensus on whether automatically generated PTTT scores that are higher than deemed reasonable by healthcare professionals according to their professional experience and clinical expertise may be downgraded. METHODS: A two-round modified Delphi technique was used to explore consensus on 14 patient cases for hospitalised children with a high PTTT score that did not raise concerns by systematically collating questionnaire responses. Participants rated their level of agreement on a 9-point Likert scale. IQR and median were calculated for each case. FINDINGS: A total of 221 participants completed round 1 and 101 participants completed round 2. Across the two rounds, majority of the participants were from paediatric departments, nurses and women. In round 1, consensus on inclusion was reached on 2 of the 14 cases. In round 2, consensus was reached on one additional patient case. Three of the 11 non-consensus cases remaining after rounds 1 and 2 were included by the research group based on predefined criteria. CONCLUSION: In conclusion, a consensus opinion was achieved on six patient cases where the child had a high PTTT score but where the healthcare professionals were not as concerned as indicated by the PTTT score.
Assuntos
Criança Hospitalizada , Pessoal de Saúde , Criança , Consenso , Técnica Delphi , Feminino , Humanos , Fatores DesencadeantesRESUMO
BACKGROUND: Since 2015, when the first cystic fibrosis transmembrane conductance regulator (CFTR) modulators were approved for people with cystic fibrosis (CF) homozygous for F508del-CFTR, studies have shown improved lung function after initiation of the treatment and patients experience improved physical capacity. The aim of this study was to investigate change in exercise capacity after initiation of Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor treatment (LUM/IVA, TEZ/IVA). METHODS: We performed a single group prospective observational cohort study with follow-up at six and 12 months. The study examined change in exercise capacity in people with CF initiating treatment with LUM/IVA and TEZ/IVA, measured by cardio-pulmonary exercise testing (CPET). Inclusion criteria were people with CF homozygous for F508del-CFTR aged 12 years or older eligible for LUM/IVA and TEZ/IVA treatment from June 2017 until June 2019. Primary outcomes were change in VO2peak and maximal workload. Secondary outcomes were change in muscle strength, muscle power and body composition in a subgroup of the study population. RESULTS: A total of 91 patients were included in the analysis. The mean change in VO2peak and VO2peak divided by body weight from baseline to 12-months follow-up was 145.7 (91.2;200.2) ml/min and 1.07 (95% CI 0.19;1.95) ml/min/kg, respectively. The mean change in maximal workload between baseline and 12 months was 14.2 Watt (95% CI 9.1;19.2). All improvements in exercise capacity were statistically significant. CONCLUSIONS: Patients in this study improved their exercise capacity by a statistically significant increase in VO2peak and maximal workload 12 months after initiation of treatment with LUM/IVA and TEZ/IVA.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Aminofenóis/uso terapêutico , Aminopiridinas/uso terapêutico , Toxinas Bacterianas , Benzodioxóis/uso terapêutico , Fibrose Cística/diagnóstico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Dinamarca , Combinação de Medicamentos , Teste de Esforço , Tolerância ao Exercício , Humanos , Indóis , Mutação , Estudos Prospectivos , QuinolonasRESUMO
AIM: Newborn screening represents a paradigm shift in the treatment of children with cystic fibrosis. This study aimed to explore parents' everyday life experiences from the time of diagnosis and in the following months. METHODS: Narrative interviews were conducted at Aarhus University Hospital, Denmark, with parents (mothers = 15 and fathers =14) of 15 term-born children with a mean age of 2 weeks (range 1-3.5 weeks). Participant observation and field notes were used to complement interview data. The analysis was inspired by Kvale and Brinkmann. RESULTS: Three themes were identified. First, on diagnosis, a profound difference in parents' experience was observed depending on whether the diagnosis was communicated by a medical doctor from the cystic fibrosis team or by a paediatrician from another hospital. Second, during the initial meetings and subsequent relationships with the cystic fibrosis team, the knowledge and calmness exhibited by the doctors and nurses were very valuable. Third, regarding everyday life after the diagnosis, most parents described experiencing anxiety and concern for their child's future. CONCLUSION: The parents' experiences highlighted essential elements that should be implemented to optimise the patient care pathway as they are fundamental to parents' ability to cope with the new living conditions.
Assuntos
Fibrose Cística , Adaptação Psicológica , Criança , Fibrose Cística/diagnóstico , Feminino , Humanos , Recém-Nascido , Mães , Triagem Neonatal , PaisRESUMO
BACKGROUND: Nasal tracheal aspiration (NTA) is a frequently used diagnostic method to assess of infections in the lower airways. However, the validity of the method has not previously been compared to bronchoalveolar lavage (BAL) in non-intubated children with a lung disease. We hypothesised that NTA performed by health professionals using the nares vocal cord distance to be placed at the entrance of the trachea, will result in same finding of bacteria in the lower airways as the gold standard of BAL. METHODS: In a prospective study, 173 paired samples of NTA and BAL were obtained between June 2016 to August 2018. Samples were collected from all patients undergoing bronchoscopy with spontaneous breathing during general anaesthesia. This study compares the microbiological results from the cultures obtained by investigating complete concordance i.e. identical pathogenic bacteria and coherence i.e. absence or presence of pathogenic bacteria growth between NTA and BAL. RESULTS: Samples were collected in 164 patients, 158 children between 21 days and 18 years of age and six young adults still treated at the paediatric department. The overall similarity (complete agreement) was found in 49% [41-56], sensitivity was 35% [27-45], specificity was 66% [55-76], positive predictive value was 36% [27-46] and negative predictive value was 64% [54-64] concerning complete pathogenic bacteria concordance. If we only considered coherence growth of pathogenic bacteria, similarity was 71% [63-79], sensitivity was 74% [64-81], specificity was 66% [55-76], positive predictive value was 75% [65-82] and negative predictive value was 65% [54-75]. Patients with cystic fibrosis showed a similarity of 88% [73-95], a sensitivity of 92% [76-99], a specificity of 71% [36-95], a positive predictive value of 92% [76-99] and a negative predictive value of 71% [36-95] concerning coherence growth of pathogenic bacteria. CONCLUSION: The study indicates that NTA compared to BAL as the gold standard is not clinically useful to assess positive findings of specific bacteria in the lower airway tract. Statistically significantly increased sensitivity and positive predictive value were found in cystic fibrosis patients concerning coherence growth. The clinical usage of NTA remains important as negative findings are of clinical value. However, BAL continues to be preferred as a significantly superior diagnostic tool.
Assuntos
Fibrose Cística , Bactérias , Lavagem Broncoalveolar , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , Criança , Fibrose Cística/microbiologia , Humanos , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). METHODS: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. RESULTS: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). CONCLUSIONS: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination.
Assuntos
COVID-19/epidemiologia , Fibrose Cística/complicações , Adolescente , Adulto , COVID-19/diagnóstico , COVID-19/terapia , Criança , Pré-Escolar , Cuidados Críticos , Fibrose Cística/mortalidade , Fibrose Cística/terapia , Europa (Continente)/epidemiologia , Feminino , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes. METHODS: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis. RESULTS: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24â years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40â years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function). CONCLUSION: SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1â s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.
RESUMO
BACKGROUND: Several studies have assessed safety and efficacy outcomes for lumacaftor/ivacaftor therapy. We report on lumacaftor/ivacaftor's impact on lung function, physical performance, and health-related quality of life (HRQOL) in a subpopulation of Danish people with Cystic Fibrosis (CF; PWCF) with advanced pulmonary disease who would not fulfill inclusion criteria for these studies. METHODS: This follow-up study examined lumacaftor/ivacaftor's effect in a highly selected CF population. Inclusion criteria included low percent predicted forced expiratory volume in one second (ppFEV1 ), fast deteriorating ppFEV1 , low body mass index (BMI), and difficult-to-treat infections. Primary endpoints included change in ppFEV1 slope, cardiopulmonary exercise testing (CPET), and all domains of the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Secondary outcomes included change in ppFEV1 , BMI Z-score, and sweat chloride concentration. RESULTS: A total of 21 patients homozygous for the F508del mutation and a median ppFEV1 of 38.7 were included. We found significant improvements in ppFEV1 (+4.2 p < .01, +5.8 p < .01, +4.8 p < .01 and +3.8 p = .03 ppFEV1 after 3, 6, 9, and 12 months of treatment compared to baseline), ppFEV1 slope (+6.84 ppFEV1 /year between the year before and the year after treatment initiation; p = .02), and saturation at CPET initiation (+1.4%, p < .02) and termination (+2.6%, p < .01) after 6 months of treatment. Finally, HRQOL improved significantly in all CFQ-R domains except Emotion and Treat. CONCLUSIONS: Our findings suggest that lumacaftor/ivacaftor reduces lung function decline, improves lung function, physical performance, and HRQOL to a greater extent in PWCF with severe lung disease than previously recognized.
Assuntos
Aminofenóis/uso terapêutico , Aminopiridinas/uso terapêutico , Benzodioxóis/uso terapêutico , Agonistas dos Canais de Cloreto/uso terapêutico , Fibrose Cística/tratamento farmacológico , Quinolonas/uso terapêutico , Adolescente , Adulto , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/agonistas , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Combinação de Medicamentos , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Adulto JovemRESUMO
AIM: Denmark has a high standard cystic fibrosis care. However, newborn screening was not implemented until 2016. This article describes the clinical status of cystic fibrosis patients at time of diagnosis prior to newborn screening. METHODS: Patients diagnosed with cystic fibrosis in Denmark in 2010-2014 were reviewed using the Danish Cystic Fibrosis Registry as well as patient files. Parameters collected were age at diagnosis, gender, weight, height, forced expiratory volume at 1 second, cystic fibrosis transmembrane regulator-genotype, lung bacteriology at diagnosis and previous diagnoses. RESULTS: A total of 63 patients were diagnosed in the study period. The most typical pre-cystic fibrosis diagnoses were asthma and pneumonia. The median age at diagnosis was 1.4 years for the pancreatic insufficient and 27.3 years for the pancreatic sufficient patients. Of the pancreatic insufficient patients, 21% had moderate to severe malnutrition with BMI below minus 2 SD and 40% had moderate to severe stunting with height below minus 2 SD. CONCLUSION: Diagnosis was delayed considerably compared to diagnosis by newborn screening in other countries. Many cystic fibrosis patients diagnosed due to clinical symptoms were moderately to severely underweight or stunted at diagnosis.
Assuntos
Fibrose Cística/diagnóstico , Diagnóstico Tardio , Adolescente , Adulto , Criança , Pré-Escolar , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/microbiologia , Dinamarca/epidemiologia , Humanos , Lactente , Recém-Nascido , Desnutrição/etiologia , Triagem Neonatal , Estado Nutricional , Adulto JovemRESUMO
PURPOSE: Pediatric early warning systems (PEWS) are used to detect clinical deterioration in hospitalized children. Few PEWSs have been validated in multicenter studies and the performance in many single-center studies varies. We wanted to compare two PEWS in a multicenter study. DESIGN AND METHODS: Randomized multicenter unblinded trial conducted at all pediatric departments in the Central Denmark Region. A random sample of 16,213 pediatric patients (31,337 admissions) were enrolled from November 2014 to March 2017. Patients were randomized to The Bedside PEWS or CDR PEWS. The primary outcome was the sum of hospitalized children experiencing in-hospital clinical deterioration requiring transfer to a higher level of care. RESULTS: Of the 21,077 pediatric patients who met the inclusion criteria, 16,213 (from 31,337 admissions) were enrolled. 22 unplanned transfers to a higher level of care were identified: 14 in The Bedside PEWS group and 8 in the CDR PEWS group, a non-statistical difference (Pâ¯=â¯0.20). No significant difference in predicting unplanned transfer to a higher level of care (Pâ¯=â¯0.78) were detected and no significant difference was observed in the secondary outcomes. CONCLUSIONS: The CDR PEWS prevents as many critical events as The Bedside PEWS. Shorter median time to PEWS reassessment when CDR PEWS was used and fewer reassessments being done to late could reflect that the CDR PEWS was more acceptable to staff. PRACTICE IMPLICATIONS: The results from this study should be interpreted with caution as very few patients experiencing clinical deterioration and further studies should also focus on challenges trying to evaluate PEWS.
Assuntos
Conscientização , Cuidados Críticos/organização & administração , Diagnóstico Precoce , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estado Terminal/terapia , Dinamarca , Progressão da Doença , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/organização & administração , Masculino , Enfermagem Pediátrica/organização & administração , Curva ROC , Medição de Risco , Índice de Gravidade de DoençaRESUMO
Few studies have described the various reasons for unplanned transfer to a higher level of care due to clinical deterioration and the clinical profile of those paediatric patients. However, an understanding of the nature of illness is important to patient safety. This study aimed to describe the frequency and clinical characteristics of children who experience unplanned transfer to a higher level of care due to clinical deterioration. A retrospective, descriptive registry study design was used. Of the 92 paediatric patients included, 69% (n = 64) was male. The median age was 2.1 years (interquartile range 0.4-6.9) with 33% being infants under 1 year. The highest number (61.3%) of transfers occurred between 8 and 16 hours. In the 24 hours leading up to a transfer due to clinical deterioration, 15 patients had no vital parameters documented, and 77 patients had least one vital parameter measured. Physiological abnormalities were present in 19 (37.7%) of the 77 patients where vital parameters were documented. This study provides essential baseline data to inform further research to improve care and treatment for critically ill children in paediatric wards. This study's findings suggest reporting of vital parameters is incomplete and infrequent.
Assuntos
Deterioração Clínica , Estado Terminal , Transferência de Pacientes , Sinais Vitais/fisiologia , Pré-Escolar , Dinamarca , Feminino , Hospitais , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Masculino , Estudos RetrospectivosRESUMO
PURPOSE: Pediatric early warning score (PEWS) systems are used to monitor pediatric patients' vital signs and facilitate the treatment of patients at risk of deteriorating. The aim of this study was to gain knowledge about nurses' experiences with PEWS and to highlight factors facilitating and impeding the use of PEWS tools in clinical practice. DESIGN AND METHODS: An exploratory qualitative design was chosen using focus group interviews to gain a deeper understanding of nurses' experiences with PEWS. A total of five focus group interviews were conducted at three hospitals, and a qualitative meaning condensation analysis as described by Kvale and Brinkmann was performed. RESULTS: Seven themes were identified, including i) lack of interdisciplinary awareness, ii) clinical judgment and PEWS-a multi-faceted approach, iii) PEWS supports a professional language, iv) monitoring the patient's - a challenge, v) PEWS helps to visualize the need for escalating care, vi) an inflexible and challenging tool, and vii) supportive tools enhance the nurses' experiences of PEWS positively. CONCLUSIONS: Our findings suggest that attention should be given to nurses' perceptions of how both clinical judgment and PEWS should be seen as essential in providing nurses with information about the patients' conditions. If not, the risk of failing to recognize patients' deteriorating conditions will remain as this can have an impeding influence on nurses' use of PEWS. From the nurses' perspective, medical doctors seemed unaware of their role in using PEWS.
RESUMO
BACKGROUND: Patients' evolving critical illness can be predicted and prevented. However, failure to identify the signs of critical illness and subsequent lack of appropriate action for patients developing acute and critical illness remain a problem. Challenges in assessing whether a child is critically ill may be due to children's often uncharacteristic symptoms of serious illness. Children may seem relatively unaffected until shortly before circulatory and respiratory failure and cardiac arrest. The Bedside Paediatric Early Warning Score has been validated in a large multinational study and is used in two regions in Denmark. However, healthcare professionals experience difficulties in relation to measuring blood pressure and to the lack of assessment of children's level of consciousness. In addition, is it noteworthy that in 23,288-hour studies, all seven items of the Bedside Paediatric Early Warning Score were recorded in only 5.1% of patients. This trial aims to compare two Paediatric Early Warning Score (PEWS) models to identify the better model for identifying acutely and critically ill children. The hypothesis is that the Central Denmark Region PEWS model is superior to the Bedside PEWS in terms of reducing unplanned transfers to intensive care or transfers from regional hospitals to the university hospital among already hospitalised children. METHODS/DESIGN: This is a multicentre, randomised, controlled clinical trial where children are allocated to one of two different PEWS models. The study involves all paediatric departments and one emergency department in the Central Denmark Region. The primary outcome is unplanned transfer to the paediatric intensive care unit or transfer from regional hospitals to the university hospital. Based on preliminary data, 14,000 children should be included to gain a power of 80% (with a 5% significance level) and to detect a clinically significant difference of 30% of unplanned transfers to intensive care or from regional hospitals to the paediatric department at the university department. A safety interim analysis will be performed after inclusion of 7000 patients. DISCUSSION: This is the first randomised trial to investigate two different PEWS models. This study demonstrates the safety and effectiveness of a new PEWS model and contributes to knowledge of hospitalised children's clinical deterioration. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02433327 . Registered on 27 April 2015.