RESUMO
BACKGROUND AND OBJECTIVE: Indwelling pleural catheter (IPC) and indwelling peritoneal catheter (IPeC) have established roles in the management of malignant pleural and peritoneal effusions but catheter-related infections remain a major concern. Topical mupirocin prophylaxis has been shown to reduce peritoneal dialysis catheter infections. This study aimed to assess the (i) compatibility of IPC with mupirocin and (ii) feasibility, tolerability and compliance of topical mupirocin prophylaxis in patients with an IPC or IPeC. METHODS: (i) Three preparations of mupirocin were applied onto segments of IPC thrice weekly and examined with scanning electron microscope (SEM) at different time intervals. (ii) Consecutive patients fitted with IPC or IPeC were given topical mupirocin prophylaxis to apply to the catheter exit-site following every drainage/dressing change (at least twice weekly) and followed up for 6 months. RESULTS: (i) No detectable structural catheter damage was found with mupirocin applied for up to 6 months. (ii) Fifty indwelling catheters were inserted in 48 patients for malignant pleural (n = 41) and peritoneal (n = 9) effusions. Median follow-up was 121 [median, IQR 19-181] days. All patients tolerated mupirocin well; one patient reported short-term local tenderness. Compliance was excellent with 95.8% of the 989 scheduled doses delivered. Six patients developed catheter-related pleural (n = 3), concurrent peritoneal/local (n = 1) and skin/tract (n = 2) infections from Streptococcus mitis (with Bacillus species or anaerobes), Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. CONCLUSION: This first study of long-term prevention of IPC- or IPeC-related infections found topical mupirocin prophylaxis feasible and well tolerated. Its efficacy warrants future randomized studies.
Assuntos
Infecções Relacionadas a Cateter , Mupirocina , Humanos , Mupirocina/uso terapêutico , Antibacterianos/uso terapêutico , Cateteres de Demora/efeitos adversos , Projetos Piloto , Administração Tópica , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/etiologia , DrenagemRESUMO
Survival statistics, estimated using data from national cystic fibrosis (CF) registries, inform the CF community and monitor disease progression. This study aimed to estimate survival among people with CF in Australia and to identify factors associated with survival. This population-based cohort study used prospectively collected data from 23 Australian CF centres participating in the Australian CF Data Registry (ACFDR) from 2005-2020. Period survival analysis was used to calculate median age of survival estimates for each 5-year window from 2005-2009 until 2016-2020. The overall median survival was estimated using the Kaplan-Meier method. Between 2005-2020 the ACFDR followed 4,601 people with CF, noting 516 (11.2%) deaths including 195 following lung transplantation. Out of the total sample, more than half (52.5%) were male and 395 (8.6%) had undergone lung transplantation. Two thirds of people with CF (66.1%) were diagnosed before six weeks of age or by newborn/prenatal screening. The overall median age of survival was estimated as 54.0 years (95% CI: 51.0-57.04). Estimated median survival increased from 48.9 years (95% CI: 44.7-53.5) for people with CF born in 2005-2009, to 56.3 years (95% CI: 51.2-60.4) for those born in 2016-2020. Factors independently associated with reduced survival include receiving a lung transplant, having low FEV1pp and BMI. Median survival estimates are increasing in CF in Australia. This likely reflects multiple factors, including newborn screening, improvement in diagnosis, refinements in CF management and centre-based multidisciplinary care.
Assuntos
Fibrose Cística , Transplante de Pulmão , Adolescente , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Austrália/epidemiologia , Estudos de Coortes , Fibrose Cística/epidemiologia , Fibrose Cística/cirurgia , Triagem NeonatalRESUMO
BACKGROUND: Treatment for pulmonary exacerbations of cystic fibrosis (CF) can produce a range of positive and negative outcomes. Understanding which of these outcomes are achievable and desirable to people affected by disease is critical to agreeing to goals of therapy and determining endpoints for trials. The relative importance of outcomes resulting from treatment of these episodes are not reported. We aimed to (i) quantify the relative importance of outcomes resulting from treatment for pulmonary exacerbations and (ii) develop patient and proxy carer-reported weighted outcome measures for use in adults and children, respectively. METHODS: A discrete choice experiment (DCE) survey was conducted. Participants were asked to make a series of hypothetical decisions about treatment for pulmonary exacerbations to assess how they make trade-offs between different attributes of health. Data were analysed using a conditional logistic regression model. The correlation coefficients from these data were rescaled to enable generation of a composite health outcome score between 0 and 100 (worst to best health state). RESULTS: 362 individuals participated (167 people with CF and 195 carers); of these, 206 completed the survey (56.9%). Most participants were female and resided in Australia. Difficult/painful breathing had the greatest impact on the preferred health state amongst people with CF and carers alike. Avoidance of gastrointestinal problems also heavily influenced decision-making. CONCLUSIONS: These data should be considered when making treatment decisions and determining endpoints for trials. Further research is recommended to quantify the preferences of children and to determine whether these align with those of their carer(s).
Assuntos
Fibrose Cística , Adulto , Austrália/epidemiologia , Criança , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/terapia , Feminino , Humanos , Pulmão , Masculino , Avaliação de Resultados em Cuidados de SaúdeRESUMO
BACKGROUND: A standardised framework for selecting outcomes for evaluation in trials has been proposed by the Core Outcome Measures in Effectiveness Trials working group. However, this method does not specify how to ensure that the outcomes that are selected are causally related to the disease and the health intervention being studied. Causal network diagrams may help researchers identify outcomes that are both clinically meaningful and likely to be causally dependent on the intervention, and endpoints that are, in turn, causally dependent on those outcomes. We aimed to (1) develop a generalisable method for selecting outcomes and endpoints in trials and (2) apply this method to select outcomes for evaluation in a trial investigating treatment strategies for pulmonary exacerbations of cystic fibrosis (CF). METHODS: We conducted a series of online surveys and workshops among people affected by CF. We used a modified Delphi approach to develop a consensus list of important outcomes. A workshop involving domain experts elicited how these outcomes were causally related to the underlying pathophysiological processes. Meaningful outcomes were prioritised based on the extent to which each outcome captured separate rather than common aspects of the underlying pathophysiological process. RESULTS: The 10 prioritised outcomes were: breathing difficulty/pain, sputum production/clearance, fatigue, appetite, pain (not related to breathing), motivation/demoralisation, fevers/night sweats, treatment burden, inability to meet personal goals and avoidance of gastrointestinal symptoms. CONCLUSIONS: This proposed method for selecting meaningful outcomes for evaluation in clinical trials may improve the value of research as a basis for clinical decisions.
Assuntos
Fibrose Cística , Fibrose Cística/diagnóstico , Fibrose Cística/terapia , Humanos , Pulmão , Terapia RespiratóriaRESUMO
Allergic bronchopulmonary aspergillosis (ABPA) is common in cystic fibrosis (CF). Treatment is challenging and the relapse rate is high. Standard therapy is oral steroids and antifungals. However, long-term systemic steroid often results in adverse effects and drug interactions between azoles and CFTR modulators are a potential concern. Mepolizumab, an anti-interleukin (IL)-5 monoclonal antibody, can benefit patients with severe eosinophilic asthma and there are reports of mepolizumab use in ABPA but not in ABPA complicating CF. We present the case of an adult with CF who had recurrent ABPA and intolerable treatment side effects with steroid, azole, and omalizumab. Mepolizumab was well tolerated and led to significantly improved clinical stability and symptomatic improvement. To our knowledge, this is the first report of successful mepolizumab treatment for ABPA in CF. Mepolizumab may be an important adjunctive treatment for difficult to control ABPA in CF.
RESUMO
BACKGROUND: Respiratory exacerbations impair lung function and health-related quality of life in people with CF, with delayed identification of exacerbations often resulting in worse outcomes. We developed a smartphone application (app) for adults with CF to report symptoms to the CF team, and investigated its impact on antibiotic use and other outcomes. METHODS: Participants were randomised to intervention (use of the app weekly or sooner if symptoms had worsened) or control (usual care). The app comprised questions relating to symptoms suggestive of an exacerbation. If worsening symptoms were reported, the participant was contacted by the nurse practitioner. The primary outcome measure was the number of courses and days of intravenous (IV) antibiotics. RESULTS: Sixty participants (29 female, aged [mean⯱â¯SD] 31⯱â¯9â¯years, FEV1 60⯱â¯18% predicted) were recruited, with 29 (48%) allocated to the intervention group. Over the 12-month follow-up, there was no clear effect of the app on the number of courses of IV antibiotics (incidence rate ratio [IRR] 1; 95% confidence interval [CI] 0.6 to 1.7), however number of courses of oral antibiotics increased (IRR 1.5; 95% CI 1.0 to 2.2). The median [IQR] time to detection of exacerbation requiring oral or IV antibiotics was shorter in the intervention group compared with the control group (70 [123] vs. 141 [140] days; pâ¯=â¯.02). No between-group differences were observed in other outcomes. CONCLUSION: The use of an app reduced time to detect respiratory exacerbations that required antibiotics, however did not demonstrate a clear effect on the number of courses of IV antibiotics.
Assuntos
Antibacterianos/administração & dosagem , Fibrose Cística , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Smartphone , Avaliação de Sintomas , Telemedicina , Administração Intravenosa/métodos , Administração Intravenosa/estatística & dados numéricos , Adulto , Fibrose Cística/diagnóstico , Fibrose Cística/fisiopatologia , Diagnóstico Precoce , Intervenção Médica Precoce/métodos , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Autorrelato/estatística & dados numéricos , Software , Avaliação de Sintomas/métodos , Avaliação de Sintomas/estatística & dados numéricos , Exacerbação dos Sintomas , Telemedicina/instrumentação , Telemedicina/métodosRESUMO
INTRODUCTION: In people with cystic fibrosis (CF), exacerbations have been shown to have profound and prolonged negative effects such as reducing physical activity and health-related quality of life, increasing the rate of decline of lung function and healthcare costs, and ultimately increasing the risk of mortality. Delayed initiation of treatment following the signs of an exacerbation has been shown to be associated with failure to recover to baseline. Therefore, the late identification and treatment of an exacerbation due to delayed presentation will potentially worsen short-term and long-term outcomes. We have developed a smartphone application, containing questions which require yes or no responses relating to symptoms suggestive of a respiratory exacerbation. Its use is intended to facilitate the early identification of symptoms suggestive of a respiratory exacerbation, and allow the CF team to initiate treatment sooner, thereby potentially reducing the risk of severe exacerbations which require intravenous antibiotics (IVAB) and often a hospital admission. METHODS: We will undertake a randomised controlled trial. 60 adults with CF will be recruited and randomised to either the intervention or control group. The intervention group will use the smartphone application weekly for 12 months, or earlier than the next weekly reporting time if they feel their symptoms have worsened. The control group will continue to receive usual care, involving regular (approximately 3 monthly) CF outpatient clinic appointments. The primary outcome measure will be courses and days of IVAB. ETHICS AND DISSEMINATION: Approval was obtained from the Sir Charles Gairdner Group Human Research Ethics Committee for WA Health (2015-030) and Curtin University Human Research Ethics Committee (HR212/2015), and has been registered with the Australian and New Zealand Clinical Trials Registry. Results of this study will be presented at international conferences and published in peer-reviewed journals in accordance with the Consolidated Standards of Reporting Trials statement. TRIAL REGISTRATION NUMBER: ACTRN12615000599572.
Assuntos
Fibrose Cística , Autorrelato , Smartphone , Avaliação de Sintomas , Adulto , Austrália , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Humanos , Nova Zelândia , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Introduction In cystic fibrosis, exacerbations impair lung function and health-related quality of life, increase healthcare costs and reduce survival. Delayed reporting of worsening symptoms can result in more severe exacerbations and worse clinical outcomes; therefore there is a need for a novel approach to facilitate the early identification and treatment of exacerbations in this population. This study investigated the usability of a smartphone application to report symptoms in adults with cystic fibrosis, and the observer agreement in clinical decision-making between senior clinicians interpreting smartphone application responses. Methods Adults with cystic fibrosis used the smartphone application weekly for four weeks. The application comprised 10 yes/no questions regarding respiratory symptoms and two regarding emotional well-being. Usability was measured with the System Usability Scale; Observer agreement was tested by providing a cystic fibrosis physician and a nurse practitioner with 45 clinical scenarios. For each scenario the clinicians, who were blinded to each other's responses, were asked to indicate whether or not they would: (i) initiate telephone contact, and/or (ii) request a clinic visit for the individual. Results Ten participants (five female), aged mean (SD) 33 (11) years, FEV1 49 (27)% predicted completed the study. The mean (SD) System Usability Scale score was 94 (6). There was perfect agreement between clinicians for initiating contact with the participant ( κ = 1.0, p < 0.001), and near-perfect for requesting a clinic visit ( κ = 0.86, p < 0.001). Discussion The use of a smartphone application for reporting symptoms in adults with cystic fibrosis has excellent usability and near-perfect agreement between senior clinicians when interpreting the application responses.
Assuntos
Fibrose Cística/fisiopatologia , Smartphone , Software , Adulto , Comunicação , Feminino , Humanos , Masculino , Qualidade de Vida , Telemedicina , Adulto JovemRESUMO
Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1s [ppFEV1] <40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV1: 34 [31-36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV1 from baseline at 2-hours (median [IQR] relative change: -19 [-21 to -11]%, p<0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV1<40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease.
Assuntos
Aminofenóis , Aminopiridinas , Benzodioxóis , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística , Monitoramento de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Dispneia , Quinolonas , Adulto , Aminofenóis/administração & dosagem , Aminofenóis/efeitos adversos , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Austrália , Benzodioxóis/administração & dosagem , Benzodioxóis/efeitos adversos , Fibrose Cística/diagnóstico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Dispneia/diagnóstico , Dispneia/etiologia , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Moduladores de Transporte de Membrana/administração & dosagem , Moduladores de Transporte de Membrana/efeitos adversos , Mutação , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Testes de Função Respiratória/métodos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Introduction A significant proportion (15%, n = 28) of the adults with cystic fibrosis (CF) in Western Australia (WA) live in rural and remote areas and have difficulty accessing specialist care at the state adult CF centre, located in Perth. We aimed to increase access by offering telehealth clinics, and evaluate the impact on health outcomes. Methods Telehealth clinics were offered via videoconference over a 12-month period, with uptake and satisfaction measured at the end of the intervention. Participants could still attend in person clinics at the CF centre if requested. Other outcomes comprised healthcare utilisation (HCU), spirometry, weight and health-related quality of life. Results In 21 participants, total clinic visits increased from 46 (median (range) per participant 2 (0-6)) in the 12-month period preceding the study to 100 (5 (2-8), p < 0.001) during the intervention. Of the 100 clinics in total, 66 were delivered via telehealth. Satisfaction with telehealth was high and most (94%) participants agreed that telehealth is a good way to deliver CF care. An increase in intravenous antibiotic days (incident rate ratio (IRR) 2.3, p = 0.03) and hospital admission days (IRR 3.7, p = 0.01) was observed. There was an improvement in the vitality domain of the Cystic Fibrosis Questionnaire - Revised ( p < 0.05). Discussion Telehealth had good uptake and increased clinic attendance in adults with CF living in rural and remote WA, and had high satisfaction amongst participants. The increase in HCU, resulting from increased detection and treatment of exacerbations, may improve long-term outcomes in this population.
Assuntos
Fibrose Cística/terapia , Acessibilidade aos Serviços de Saúde/organização & administração , Serviços de Saúde Rural/organização & administração , Serviços de Saúde Rural/estatística & dados numéricos , Telemedicina/organização & administração , Adulto , Peso Corporal , Feminino , Serviços de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Satisfação do Paciente , Qualidade de Vida , Espirometria , Inquéritos e Questionários , Comunicação por Videoconferência , Austrália OcidentalRESUMO
BACKGROUND AND OBJECTIVE: Flexi-rigid pleuroscopy is a useful tool in the work-up of pleural effusions, but pleural biopsy using flexible forceps can be difficult in some patients. This study evaluated the feasibility, safety and diagnostic value of using a flexible cryoprobe to obtain parietal pleural biopsies during pleuroscopy. METHODS: This was a single-centre retrospective study. In patients undergoing diagnostic pleuroscopy, pleural biopsy using flexible forceps, followed by a flexible cryoprobe introduced through the pleuroscope, were performed. A pathologist independently reviewed all biopsies. Any complications, particularly bleeding, were recorded. All patients were followed up for ≥ 6 months (median 12 months (range 7-26)). RESULTS: Twenty-two patients (21 males; median age 72 years; 14 right-sided effusions) were included. All underwent flexible forceps biopsies (FFB) and cryoprobe biopsies (CB) of pleura. FFB and CB established a definitive diagnosis in 20/22 (90%). CB successfully obtained pleural tissue suitable for histopathological analysis in all patients. CB was larger than FFB (median, 25-75 IQR of 10, 7-15.8mm vs 4, 3-8mm), and had better preserved cellular architecture and tissue integrity. Crush artefacts were less common with CB (2/22) compared with FFB (21/22). No significant bleeding was reported. CONCLUSIONS: CB during flexi-rigid pleuroscopy is feasible, safe and effective. Its routine use during flexi-rigid pleuroscopy requires further evaluation.
Assuntos
Biópsia/métodos , Criocirurgia/instrumentação , Pleura/patologia , Derrame Pleural/etiologia , Toracoscopia/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/efeitos adversos , Biópsia/instrumentação , Criocirurgia/efeitos adversos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Instrumentos Cirúrgicos , Toracoscopia/efeitos adversosRESUMO
BACKGROUND: Patients with malignant pleural effusion (MPE) have limited prognoses. They require long-lasting symptom relief with minimal hospitalization. Indwelling pleural catheters (IPCs) and talc pleurodesis are approved treatments for MPE. Establishing the implications of IPC and talc pleurodesis on subsequent hospital stay will influence patient choice of treatment. Therefore, our objective was to compare patients with MPE treated with IPC vs pleurodesis in terms of hospital bed days (from procedure to death or end of follow-up) and safety. METHODS: In this prospective, 12-month, multicenter study, patients with MPE were treated with IPC or talc pleurodesis, based on patient choice. Key end points were hospital bed days from procedure to death (total and effusion-related). Complications, including infection and protein depletion, were monitored longitudinally. RESULTS: One hundred sixty patients with MPE were recruited, and 65 required definitive fluid control; 34 chose IPCs and 31 pleurodesis. Total hospital bed days (from any causes) were significantly fewer in patients with IPCs (median, 6.5 days; interquartile range [IQR] = 3.75-13.0 vs pleurodesis, mean, 18.0; IQR, 8.0-26.0; P = .002). Effusion-related hospital bed days were significantly fewer with IPCs (median, 3.0 days; IQR, 1.8-8.3 vs pleurodesis, median, 10.0 days; IQR, 6.0-18.0; P < .001). Patients with IPCs spent significantly fewer of their remaining days of life in hospital (8.0% vs 11.2%, P < .001, χ(2) = 28.25). Fewer patients with IPCs required further pleural procedures (13.5% vs 32.3% in pleurodesis group). There was no difference in rates of pleural infection (P = .68) and protein (P = .65) or albumin loss (P = .22). More patients treated with IPC reported immediate (within 7 days) improvements in quality of life and dyspnea. CONCLUSIONS: Patients treated with IPCs required significantly fewer days in hospital and fewer additional pleural procedures than those who received pleurodesis. Safety profiles and symptom control were comparable.
Assuntos
Cateteres de Demora , Drenagem/instrumentação , Tempo de Internação , Derrame Pleural Maligno/terapia , Pleurodese , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Preferência do Paciente , Projetos Piloto , Derrame Pleural Maligno/complicações , Derrame Pleural Maligno/patologia , Estudos Prospectivos , Talco/administração & dosagem , Resultado do TratamentoRESUMO
We aimed to examine the relationship between levels of socio-economic disadvantage (measured by the Socio Economic Indexes for Areas [SEIFA] used by the Australian Bureau of Statistics) and uptake of the Enhanced Primary Care (EPC) item numbers on the Medicare Benefits Schedule. Health services are often less likely to reach those that most need them and so it is important to monitor whether disadvantaged communities are accessing EPC The rates of health assessments, care plans and case conferences are similar in each SEIFA quartile (from advantaged to disadvantaged populations), favouring the more disadvantaged quartiles in some cases. These national trends are not observed in each state and territory. For all EPC services combined, the lowest number of doctors that provide EPC services are found in the 2 most disadvantaged quartiles, yet more EPC services are provided in these quartiles, due to the higher mean and median number of services provided by general practitioners in these quartiles. Overall, populations living in the most disadvantaged quartiles have similar or higher levels of EPC uptake, apparently due, at least in part, to greater than average use of EPC services by general practitioners in these areas.
Assuntos
Doença Crônica/economia , Programas Nacionais de Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Populações Vulneráveis/estatística & dados numéricos , Austrália , Bases de Dados Factuais , Governo Federal , Pesquisa sobre Serviços de Saúde , Humanos , Avaliação das Necessidades , Atenção Primária à Saúde/economia , Análise de Pequenas Áreas , Fatores SocioeconômicosRESUMO
We aimed to describe the uptake of the Enhanced Primary Care (EPC) item numbers listed on the Medicare Benefits Schedule for health assessment (HA), care plan (CP) and case conference (CC) between November 1999 (when these items first became available) and October 2001. We used data provided by the Commonwealth Department of Health and Ageing. General practitioners rendered 371,409 EPC services in all. Most services were HA (225,353; 61%), most of the remainder were CP (134,688; 36%), and CC comprised the rest (11,368; 3%). The number of HA done increased steadily and has stabilised at around 13,000 HA per month. Most CP done (80%) were in the community and with the GP preparing the plan. From a slow start, the number of CP done increased rapidly in 2001 to about 15,000 per month. There has been a slow and steady increase in the number of CC done each month, reaching 8-900 per month. Uptake of the EPC item numbers in the first two years of their availability has been rapid and has reached substantial levels, especially for HA and CP. The uptake of CC has been slower.