A RCT to explore the effectiveness of supporting adherence to nebuliser medication in adults with cystic fibrosis: fidelity assessment of study interventions.

BACKGROUND: A multi-component self-management intervention 'CFHealthHub' was developed to reduce pulmonary exacerbations in adults with Cystic Fibrosis (CF) by supporting adherence to nebuliser medication. It was evaluated in a randomized controlled trial (RCT) involving 19 CF centres, with 32 interventionists, 305 participants in the intervention group, and 303 participants in the standard care arm. Ensuring treatment fidelity of intervention delivery was crucial to ensure that the intervention produced the expected outcomes. METHODS: Fidelity of the CFHealthHub intervention and standard care was assessed using different methods for each of the five fidelity domains defined by the Borrelli framework: study design, training, treatment delivery, receipt, and enactment. Study design ensured that the groups received the intended intervention or standard care. Interventionists underwent training and competency assessments to be deemed certified to deliver the intervention. Audio-recorded intervention sessions were assessed for fidelity drift. Receipt was assessed by identifying whether participants set Action and Coping Plans, while enactment was assessed using click analytics on the CFHealthHub digital platform. RESULTS: Design: There was reasonable agreement (74%, 226/305) between the expected versus actual intervention dose received by participants in the CFHealthHub intervention group. The standard care group did not include focused adherence support for most centres and participants. Training: All interventionists were trained. Treatment delivery: The trial demonstrated good fidelity (overall fidelity by centre ranged from 79 to 97%), with only one centre falling below the mean threshold (> 80%) on fidelity drift assessments. Receipt: Among participants who completed the 12-month intervention, 77% (205/265) completed at least one action plan, and 60% (160/265) completed at least one coping plan. Enactment: 88% (268/305) of participants used web/app click analytics outside the intervention sessions. The mean (SD) number of web/app click analytics per participant was 31.2 (58.9). Additionally, 64% (195/305) of participants agreed to receive notifications via the mobile application, with an average of 53.6 (14.9) notifications per participant. CONCLUSIONS: The study demonstrates high fidelity throughout the RCT, and the CFHealthHub intervention was delivered as intended. This provides confidence that the results of the RCT are a valid reflection of the effectiveness of the CFHealthHub intervention compared to standard care. TRIAL REGISTRATION: ISRCTN registry: ISRCTN55504164 (date of registration: 12/10/2017).

Development of an intervention to increase adherence to nebuliser treatment in adults with cystic fibrosis: CFHealthHub.

BACKGROUND: Cystic fibrosis (CF) is a life-limiting genetic condition in which daily therapies to maintain lung health are critical, yet treatment adherence is low. Previous interventions to increase adherence have been largely unsuccessful and this is likely due to a lack of focus on behavioural evidence and theory alongside input from people with CF. This intervention is based on a digital platform that collects and displays objective nebuliser adherence data. The purpose of this paper is to identify the specific components of an intervention to increase and maintain adherence to nebuliser treatments in adults with CF with a focus on reducing effort and treatment burden. METHODS: Intervention development was informed by the Behaviour Change Wheel (BCW) and person-based approach (PBA). A multidisciplinary team conducted qualitative research to inform a needs analysis, selected, and refined intervention components and methods of delivery, mapped adherence-related barriers and facilitators, associated intervention functions and behaviour change techniques, and utilised iterative feedback to develop and refine content and processes. RESULTS: Results indicated that people with CF need to understand their treatment, be able to monitor adherence, have treatment goals and feedback and confidence in their ability to adhere, have a treatment plan to develop habits for treatment, and be able to solve problems around treatment adherence. Behaviour change techniques were selected to address each of these needs and were incorporated into the digital intervention developed iteratively, alongside a manual and training for health professionals. Feedback from people with CF and clinicians helped to refine the intervention which could be tailored to individual patient needs. CONCLUSIONS: The intervention development process is underpinned by a strong theoretical framework and evidence base and was developed by a multidisciplinary team with a range of skills and expertise integrated with substantial input from patients and clinicians. This multifaceted development strategy has ensured that the intervention is usable and acceptable to people with CF and clinicians, providing the best chance of success in supporting people with CF with different needs to increase and maintain their adherence. The intervention is being tested in a randomised controlled trial across 19 UK sites.

Comparing accelerometer, pedometer and a questionnaire for measuring physical activity in bronchiectasis: a validity and feasibility study?

BACKGROUND: There are challenges for researchers and clinicians to select the most appropriate physical activity tool, and a balance between precision and feasibility is needed. Currently it is unclear which physical activity tool should be used to assess physical activity in Bronchiectasis. The aim of this research is to compare assessment methods (pedometer and IPAQ) to our criterion method (ActiGraph) for the measurement of physical activity dimensions in Bronchiectasis (BE), and to assess their feasibility and acceptability. METHODS: Patients in this analysis were enrolled in a cross-sectional study. The ActiGraph and pedometer were worn for seven consecutive days and the IPAQ was completed for the same period. Statistical analyses were performed using SPSS 20 (IBM). Descriptive statistics were used; the percentage agreement between ActiGraph and the other measures were calculated using limits of agreement. Feedback about the feasibility of the activity monitors and the IPAQ was obtained. RESULTS: There were 55 (22 male) data sets available. For step count there was no significant difference between the ActiGraph and Pedometer, however, total physical activity time (mins) as recorded by the ActiGraph was significantly higher than the pedometer (mean ± SD, 232 (75) vs. 63 (32)). Levels of agreement between the two devices was very good for step count (97% agreement); and variation in the levels of agreement were within accepted limits of ±2 standard deviations from the mean value. IPAQ reported more bouted- moderate - vigorous physical activity (MVPA) [mean, SD; 167(170) vs 6(9) mins/day], and significantly less sedentary time than ActiGraph [mean, SD; 362(115) vs 634(76) vmins/day]. There were low levels of agreement between the two tools (57% sedentary behaviour; 0% MVPA10+), with IPAQ under-reporting sedentary behaviour and over-reporting MVPA10+ compared to ActiGraph. The monitors were found to be feasible and acceptable by participants and researchers; while the IPAQ was accepta ble to use, most patients required assistance to complete it. CONCLUSIONS: Accurate measurement of physical activity is feasible in BE and will be valuable for future trials of therapeutic interventions. ActiGraph or pedometer could be used to measure simple daily step counts, but ActiGraph was superior as it measured intensity of physical activity and was a more precise measure of time spent walking. The IPAQ does not appear to represent an accurate measure of physical activity in this population. TRIAL REGISTRATION: Clinical Trials Registration Number NCT01569009 : Physical Activity in Bronchiectasis.

Estrogen receptor antagonism exacerbates cardiac structural and functional remodeling in female rats.

We have previously demonstrated the cardioprotective effects of ovarian hormones against adverse ventricular remodeling imposed by chronic volume overload. Here, we assess the estrogen receptor dependence of this cardioprotection. Four groups of female rats were studied: sham-operated (Sham), volume overloaded [aortocaval fistula (ACF)], Sham treated with estrogen receptor antagonist ICI 182,780 (Sham + ICI), and ACF treated with ICI. Cardiac function was assessed temporally using echocardiogram, and tissue samples were collected at 5 days and 6 wk postsurgery. All rats with volume overload had significantly increased cardiac output (96 ± 32 ml/min for ACF and 108 ± 11 ml/min for ACF + ICI vs. 31 ± 2 for Sham, P < 0.05). At 6 wk, volume overload induced significant left ventricular (LV) hypertrophy in both untreated and treated ACF groups. Both ACF groups developed significantly increased LV end-diastolic diameter (LVEDD), indicating LV dilatation, with the ACF + ICI group having the greatest increase (340%, relative to Sham). Ejection fraction was significantly reduced in the ACF + ICI group (23% reduction) at 6 wk postsurgery compared with untreated ACF (P < 0.05). Interstitial collagen staining was significantly reduced by volume overload, with estrogen receptor antagonism causing greater collagen loss at both 5 days and 6 wk postsurgery. Furthermore, volume overload induced a significant increase in LV wall stress only in rats treated with estrogen antagonist. These data indicate that estrogen receptor signaling is essential for sex hormone-dependent cardioprotection against adverse remodeling. The maintenance of myocardial extracellular matrix collagen appears to play a key role in this cardioprotection. NEW & NOTEWORTHY: We assessed the estrogen receptor (ER) dependence of female-specific cardioprotection using a rat model of chronic volume-overload stress. ER antagonism worsened ventricular wall stress, ventricular dilation, and cardiac dysfunction induced by volume overload. Further, blocking ERs resulted in cardiac remodeling and functional changes similar to that previously found in ovariectomized rats.

Airway clearance techniques used by people with cystic fibrosis in the UK.

OBJECTIVES: To describe the current use of airway clearance techniques among people with cystic fibrosis (CF) in the UK, and the baseline characteristics for users of different airway clearance techniques. DESIGN: Analysis of the UK CF Registry 2011 data. SETTING AND PARTICIPANTS: All people with CF in the UK aged ≥11 years (n=6372). RESULTS: Of the 6372 people on the UK CF registry in 2011, 89% used airway clearance techniques. The most commonly used primary techniques were forced expiratory techniques (28%) and oscillating positive expiratory pressure (PEP) (23%). Postural drainage and high-frequency chest wall oscillation were used by 4% and 1% of people with CF, respectively. The male:female ratio of individuals who used exercise as their primary airway clearance technique was 2:1, compared with 1:1 for other techniques. Individuals with more severe lung disease tended to use devices such as non-invasive ventilation or high-frequency chest wall oscillation. CONCLUSIONS: Forced expiratory techniques and oscillating PEP are the most common airway clearance techniques used by people with CF in the UK, and postural drainage and high-frequency chest wall oscillation are the least common techniques. This is significant in terms of planning airway clearance technique trials, where postural drainage has been used traditionally as the comparator. The use of airway clearance techniques varies between countries, but the reasons for these differences are unknown.

Lung clearance index: evidence for use in clinical trials in cystic fibrosis.

The ECFS-CTN Standardisation Committee has undertaken this review of lung clearance index as part of the group's work on evaluation of clinical endpoints with regard to their use in multicentre clinical trials in CF. The aims were 1) to review the literature on reliability, validity and responsiveness of LCI in patients with CF, 2) to gain consensus of the group on feasibility of LCI and 3) to gain consensus on answers to key questions regarding the promotion of LCI to surrogate endpoint status. It was concluded that LCI has an attractive feasibility and clinimetric properties profile and is particularly indicated for multicentre trials in young children with CF and patients with early or mild CF lung disease. This is the first article to collate the literature in this manner and support the use of LCI in clinical trials in CF.

Movie making as a cognitive distraction for paediatric patients receiving radiotherapy treatment: qualitative interview study.

OBJECTIVES: To establish the outcomes achieved by using an innovative movie-making programme designed to reduce fear of radiotherapy among paediatric patients. DESIGN: Qualitative descriptive evaluation based on semistructured, qualitative interviews with purposeful sampling and thematic analysis. SETTING: Tertiary Cancer Centre. PARTICIPANTS: 20 parents of paediatric patients who had produced a movie of their radiation therapy experience and were in a follow-up phase of cancer management. RESULTS: Participants attributed a broad range of outcomes to the movie-making program. These included that the programme had helped reduce anxiety and distress exhibited by paediatric patients and contributed to a willingness to receive treatment. Other outcomes were that the completed movies had been used in school reintegration and for maintaining social connections. CONCLUSIONS: Allowing children to create a video of their experience of radiotherapy provided a range of benefits to paediatric patients that varied according to their needs. For some patients, movie-making offered a valuable medium for overcoming fear of the unknown as well as increasing understanding of treatment processes. For others, the development of a personalised video offered an important cognitive/attentional distraction through engaging with an age-appropriate activity. Together these outcomes helped children maintain self-control and a positive outlook.

Respiratory muscle pressures in non-CF bronchiectasis: repeatability and reliability.

BACKGROUND: Respiratory muscle strength is used diagnostically in clinical practice and as an outcome measure in clinical trials in various chronic lung diseases. There is limited data on its repeatability in people with non-CF bronchiectasis. The aim of the present study was to assess the repeatability of maximal inspiratory (P( I)max) and expiratory pressures (P(E)max) in a group of patients with stable, moderate-to-severe non-CF bronchiectasis. METHODS: Twenty participants with stable moderate-to-severe non-CF bronchiectasis were recruited. Respiratory muscle strength measurements (three maximal inspiratory and expiratory pressures) were made on 2 separate days. A standard protocol was used, including practice tests, before obtaining three technically acceptable and reproducible readings with a difference of 10% or less between values. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00487149. RESULTS: The mean (SD) age of the non-CF bronchiectasis group was 63 (9) years. Maximal inspiratory pressures were repeatable with mean (SD) for highest P(I)max, Test 1 and Test 2, 75.90 (20) and 79.40 (19) cmH(2)O, and limits of agreement (mean difference +/- 2SD) -3.50 +/- 20 cmH(2)O, (p = 0.14). Maximal expiratory pressures differed significantly with mean (SD) for highest P(E)max, Test 1 and Test 2, 102.25 (27) and 112.30 (32) cmH(2)O, and limits of agreement (mean difference +/- 2SD) -10.10 +/- 35 cmH(2)O, (p = 0.02). The intraclass correlation coefficient (95% CI) for highest P(I)max and P(E)max was 0.93 (95% CI 0.82 to 0.97) and 0.90 (95% CI 0.76 to 0.96), respectively. CONCLUSION: Maximal inspiratory pressure measurements were repeatable during a period of clinical stability in moderate-to-severe non-CF bronchiectasis, suggesting this may be a useful outcome measure in non-CF bronchiectasis. Once a baseline has been established, a second visit is not required. P(E)max was not a repeatable measure and further study is necessary to ascertain how much practice testing is required to obtain an accurate value.

Demographic and historical findings, including exposure to environmental tobacco smoke, in dogs with chronic cough.

BACKGROUND: Controlled studies investigating risk factors for the common presenting problem of chronic cough in dogs are lacking. HYPOTHESIS/OBJECTIVES: To identify demographic and historical factors associated with chronic cough in dogs, and associations between the characteristics of cough and diagnosis. ANIMALS: Dogs were patients of an academic internal medicine referral service. Coughing dogs had a duration of cough>or=2 months (n=115). Control dogs had presenting problems other than cough (n=104). METHODS: Owners completed written questionnaires. Demographic information and diagnoses were obtained from medical records. Demographic and historical data were compared between coughing and control dogs. Demographic data and exposure to environmental tobacco smoke (ETS) also were compared with hospital accessions and adult smoking rates, respectively. Characteristics of cough were compared among diagnoses. RESULTS: Most coughing dogs had a diagnosis of large airway disease (n=88; 77%). Tracheobronchomalacia (TBM) was diagnosed in 59 dogs (51%), including 79% of toy breed dogs. Demographic risk factors included older age, smaller body weight, and being toy breed (P<.001). No association was found between coughing and month (P=.239) or season (P=.414) of presentation. Exposure to ETS was not confirmed to be a risk factor (P=.243). No historical description of cough was unique to a particular diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Associations with age, size, and toy breeds were strong. TBM is frequent in dogs with chronic cough, but descriptions of cough should be used cautiously in prioritizing differential diagnoses. The association between exposure to ETS and chronic cough deserves additional study.

Non-invasive ventilation for cystic fibrosis.

BACKGROUND: Non-invasive ventilation (NIV) may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis (CF). OBJECTIVES: To compare the effect of NIV versus no NIV in people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials. Most recent search: October 2006. SELECTION CRITERIA: Randomised controlled trials comparing a form of pressure preset or volume preset NIV to no NIV in people with acute or chronic respiratory failure in CF. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. MAIN RESULTS: Fifteen trials were identified; seven trials met the inclusion criteria with a total of 106 participants. Six trials evaluated single treatment sessions only and one evaluated a six-week intervention. Four trials (79 participants) evaluated NIV for airway clearance compared with an alternative chest physiotherapy method and showed that airway clearance may be easier with NIV and people with CF may prefer it. We were unable to find any evidence that NIV increases sputum expectoration, but it did improve some lung function parameters.Three trials (27 participants) evaluated NIV for overnight ventilatory support. Lung function and nocturnal transcutaneous carbon dioxide were evaluated within two trials. Due to the small numbers of participants and statistical issues, there were discrepancies in the results between the RevMan and the original trial analyses. No clear differences were found between NIV compared with oxygen or room air except for exercise performance, which significantly improved with NIV compared to room air over six weeks. AUTHORS' CONCLUSIONS: Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with CF who have difficulty expectorating sputum. Non-invasive ventilation, when used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. These benefits of NIV have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in CF airway clearance and exercise.

Acapella versus 'usual airway clearance' during acute exacerbation in bronchiectasis: a randomized crossover trial.

Devices such as the Acapella may facilitate independent airway clearance, however, few clinical trials have investigated the efficacy of Acapella. The aim of this study was to compare the effectiveness of Acapella to 'usual airway clearance' in adults during an acute exacerbation of bronchiectasis requiring oral antibiotic therapy. Twenty patients with bronchiectasis and an acute exacerbation requiring oral antibiotic therapy were recruited into a randomized crossover trial. Patients were allocated to one of two groups determined by concealed computer generated randomization. Group 1 (n=10): airway clearance session using Acapella at home twice daily during oral antibiotic therapy. Group 2 (n=10): 'usual' airway clearance sessions at home during oral antibiotic therapy. Patients recorded duration of each treatment session, volume of sputum produced and perception of breathlessness. An independent assessor performed outcome measures of spirometric lung function, pulse oximetry and breathlessness at the beginning and end of the study period. The mean volume of sputum expectorated during Acapella sessions was greater than for usual airway clearance sessions although this difference was not significant 2.61 ml (95% CI-1.62 to 6.84). Mean duration of Acapella sessions was greater than usual airway clearance sessions and approached significance. There were no significant between group differences in changes in lung function. This study demonstrates that the Acapella device may offer an acceptable, user-friendly method of airway clearance in patients with bronchiectasis.

Flight assessment in patients with respiratory disease: hypoxic challenge testing vs. predictive equations.

BACKGROUND: Predictive equations have been proposed as a simpler alternative to hypoxic challenge testing (HCT) for determining the risk of in-flight hypoxia. AIM: To assess agreement between hypoxic challenge testing (HCT) and predictive equations for assessment of in-flight hypoxia. DESIGN: Retrospective study. METHODS: Patients with chronic obstructive pulmonary disease (COPD) (n = 15), interstitial lung disease (ILD) (n = 15) and cystic fibrosis (CF) (n = 15) were studied. Spirometry was recorded prior to hypoxic inhalation and oxygen saturations (SpO2) were recorded before, after and during hypoxic inhalation. Blood gases were analysed before and after hypoxic inhalation and when SpO2 = 85%. An HCT was performed using the Ventimask method. The PaO2 at altitude was estimated for each group using four published predictive equations, which use values of PaO2 (ground) and lung function measurements to predict altitude PaO2. Results were interpreted using the BTS recommendations for prescription of in-flight oxygen post HCT. The Stuart Maxwell test of overall homogeneity was used to assess agreement between HCT results and each of the predictive equations. RESULTS: Ground PaO2 was significantly greater in patients with CF than either ILD or COPD (p < 0.05). PaO2 in all three groups significantly decreased following HCT. With the exception of equation 3, significantly fewer patients in each group would require in-flight O2 if prescription was based on HCT, compared to predictive equations (p < 0.05). DISCUSSION: Predictive equations considerably overestimate the need for in-flight O2, compared to HCT.

Self-management in bronchiectasis: the patients' perspective.

Self-management programmes for chronic disease are a high priority for healthcare providers. The content and method of delivery of self-management should give consideration to the specific requirements of the disease population. The aims of the present study were to assess the physical and psychosocial impact of bronchiectasis, to determine whether patients with bronchiectasis are receptive to self-management and to identify any obstacles or sources of support for a disease-specific self-management programme. A total of 32 patients with a diagnosis of bronchiectasis attended four focus groups. Each focus group was videotaped and subjected to qualitative analysis using the grounded theory approach. Bronchiectasis had an impact on patients' physical and psychosocial well-being. Patients demonstrated the potential to self-manage with strategies including self-regulation of medication and airway clearance. Perceived obstacles to self-management included lack of information and confidence. Patients suggested that self-management could be promoted through disease-specific information and appropriate healthcare procedures. In summary, patients with bronchiectasis have their lives disrupted by this chronic condition, but are receptive to self-management. The present study has provided information from the patients' perspective of elements which need to be included in a successful disease-specific self-management programme.

Subjective benefit of inhaled therapies in patients with bronchiectasis: a questionnaire study.

The objectives of this study were to obtain information about the use and subjective benefits of inhaled therapies in patients with bronchiectasis and to determine if these benefits were related to the presence of airflow obstruction. One hundred and twenty patients completed a questionnaire on inhaled therapies and performed spirometry. Inhalers were used daily by 85/120 patients with bronchiectasis and 42/120 patients had a nebuliser. Inhaled therapies were used extensively in patients with (FEV1 < 80%) and without (FEV1 > 80%) evidence of airflow obstruction. The majority of patients reported subjective benefits from their inhaled therapies. Chi2 analysis showed that there was no association between perceived benefits of short acting bronchodilators (SAB), long acting bronchodilators (LAB), corticosteroids or nebulisers and degree of airflow obstruction. This study provides information about the subjective benefits of inhaled therapies which could facilitate a more comprehensive assessment of the net benefit of inhaled therapies in patients with bronchiectasis with and without airflow obstruction.

Airway clearance in bronchiectasis: a randomized crossover trial of active cycle of breathing techniques (incorporating postural drainage and vibration) versus test of incremental respiratory endurance.

OBJECTIVES: The purpose of this study was to compare the efficacy of the test of incremental respiratory endurance (TIRE) with active cycle of breathing techniques (ACBT) [incorporating postural drainage (PD) and vibration] as methods of airway clearance in adults with bronchiectasis. DESIGN: A randomized crossover study in which a single session of ACBT (incorporating PD and vibration) was compared to a single session of TIRE was carried out in 20 patients (14 female) with stable, productive bronchiectasis. MEASUREMENTS: Weight of sputum (treatment plus 30 min) was the primary outcome measure recorded. Pre- and post-treatment measures of lung function and SpO2 were also recorded. RESULTS: All 20 patients were stable during the study period. Sputum weight expectorated during and 30 min post-ACBT (incorporating PD and vibration) treatment was significantly greater than the sputum weight expectorated during and 30 min post-TIRE treatment [mean difference 2.44 g (95% CI 0.43-4.45)]. CONCLUSION: ACBT (incorporating PD and vibration) is a more effective method of airway clearance in bronchiectasis than TIRE during single treatment sessions.

Incontinence in adult females with cystic fibrosis: a Northern Ireland survey.

The objectives of this survey were to establish the prevalence, onset, severity and impact of incontinence and attitudes towards the availability of advice and treatment in female adults with cystic fibrosis (CF) in Northern Ireland. All female patients (n=59) at the Northern Ireland Regional Adult CF Centre were posted a questionnaire on incontinence. Leakage of urine occurred in 14/46 respondents. Leakage of urine occurred when chest was bad in 8/14 patients and when chest was good or bad in 3/14 patients. Patients reported that their bladder problem affected their ability to perform airway clearance or cough (13/14), and exercise (4/14). The main reason given for the patients who did not seek help for their incontinence (10/14) was that they were too embarrassed. This study highlights that patients with CF are reluctant to seek treatment for incontinence despite the impact this condition can have.

The current physiotherapy management of patients with bronchiectasis: a UK survey.

The purpose of this survey was to ascertain which physiotherapy techniques are currently used, how interventions are assessed and to determine the views of physiotherapists in the UK on the need for further research. Senior physiotherapists in 100 randomly selected hospitals providing respiratory care in the UK were sent a previously piloted questionnaire on their bronchiectasis practice. The response rate was 82%. A variety of physiotherapy treatment techniques and outcome measures are used, and there are no national guidelines on the physiotherapy management of patients with bronchiectasis. There is a clear need for research into the effectiveness of physiotherapy techniques in bronchiectasis including a cost-benefit analysis which would enable targeting of resources and the development of evidence-based practice guidelines.

Impact of age and gender on the pharmacokinetics of gemtuzumab ozogamicin.

STUDY OBJECTIVE: To determine the pharmacokinetic parameters of the components of gemtuzumab ozogamicin and to assess the possible influence of age and gender on the values. DESIGN: Phase II, multicenter, open-label, nonrandomized, parallel study SETTING: Hospitals and outpatient oncology clinics. PATIENTS: Fifty-eight patients with acute myeloid leukemia in first relapse participated. Demographic data included 29 men and 29 women; 34 were younger than 60 years of age (mean age 53+/-16 yrs). INTERVENTION: Patients received gemtuzumab ozogamicin as a single 2-hour infusion of 9 mg/m2. Serial plasma samples were collected over 10 days after the beginning of the infusion. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of components of gemtuzumab ozogamicin (hP67.6 antibody, total and unconjugated calicheamicin derivatives) were measured by validated enzyme-linked immunosorbent assays. Pharmacokinetic parameters were determined by noncompartmental methods and comparisons between groups were made by analysis of variance. No significant differences were seen between men and women or between those over 60 and those less than 60 years of age in maximum concentration, time to maximum concentration, area under the curve, clearance, or volume of distribution for components of gemtuzumab ozogamicin. CONCLUSION: No differences occur in the pharmacokinetics of the components of gemtuzumab ozogamicin (hP67.6 or calicheamicin) based on gender or age.