Effectiveness of the "Living with Cancer" peer self-management support program for persons with advanced cancer and their relatives: study protocol of a non-randomized stepped wedge study.

BACKGROUND: Persons with advanced cancer and their relatives experience physical, emotional, and psychosocial consequences of the illness. Most of the time, they must deal with these themselves. While peer self-management support programs may be helpful, there is little evidence on their value for this population. We present the research protocol of our SMART study that will evaluate the effectiveness of the "Living with Cancer" peer self-management support program, aimed at improving self-management behaviors, self-efficacy, and health-related quality of life of persons with advanced cancer and their relatives. METHODS: We will conduct a non-randomized stepped wedge study in the Netherlands. We will include 130 persons with advanced cancer and 32 relatives. Participants can choose to either start the program within 4 weeks after inclusion or after eight to 10 weeks. The "Living with Cancer" is a peer self-management support program, based on the Chronic Disease Self-Management Program. It consists of six 1,5 hours video-conferencing group meetings with eight to 12 participants, preceded by two or three preparatory audio clips with supportive text per session. The program has the following core components: the learning of self-management skills (action-planning, problem-solving, effective communication, and decision-making), discussing relevant themes (e.g. dealing with pain and fatigue, living with uncertainty, and future planning), and sharing experiences, knowledge, and best practices. The primary outcome for both persons with advanced cancer and relatives is self-management behavior assessed by the subscale "constructive attitudes and approaches" of the Health Education Impact Questionnaire. Secondary outcomes are other self-management behaviors, self-efficacy, health-related quality of life, symptoms, depression and anxiety, and loneliness. Participants complete an online questionnaire at baseline, and after eight and 16 weeks. After each session, they complete a logbook about their experiences. Group meetings will be video recorded. DISCUSSION: SMART aims to evaluate an innovative program building on an evidence-based self-management program. New features are its use for persons with advanced cancer, the inclusion of relatives, and the video-conferencing format for this population. The use of both quantitative and qualitative analyses will provide valuable insight into the effectiveness and value of this program. TRIAL REGISTRATION: This study was registered in the Dutch Trial Register on October 2021, identifier NL9806 .

Small airway deposition of dornase alfa during exacerbations in cystic fibrosis; a randomized controlled clinical trial.

INTRODUCTION: Small airway obstruction is important in the pathophysiology of cystic fibrosis (CF) lung disease. Additionally, many CF patients lose lung function in the long term as a result of respiratory tract exacerbations (RTEs). No trials have been performed to optimize mucolytic therapy during a RTE. We investigated whether specifically targeting dornase alfa to the small airways improves small airway obstruction during RTEs. METHODS: In a multi-center, double-blind, randomized controlled trial CF patients hospitalized for a RTE and on maintenance treatment with dornase alfa were switched to a smart nebulizer. Patients were randomized to small airway deposition (n = 19) or large airway deposition (n = 19) of dornase alfa for at least 7 days. Primary endpoint was forced expiratory flow at 75% of forced vital capacity (FEF75 ). MAIN RESULTS: Spirometry parameters improved significantly during admission, but the difference in mean change in FEF75 between treatment groups was not significant: 0.7 SD, P = 0.30. FEF25-75 , FEV1 , nocturnal oxygen saturation and diary symptom scores also did not differ between groups. CONCLUSIONS: This study did not detect a difference if inhaled dornase alfa was targeted to small versus large airways during a RTE. However, the 95% confidence interval for the change in FEF75 was wide. Further studies are needed to improve the effectiveness of RTE treatment in CF.

Determining presence of lung disease in young children with cystic fibrosis: lung clearance index, oxygen saturation and cough frequency.

BACKGROUND: Accurate assessment of pulmonary status in young children with cystic fibrosis (CF) requires sensitive and objective monitoring techniques. OBJECTIVES: This study aimed to evaluate the feasibility of lung clearance index (LCI) calculated from multiple breath washout (MBW), home nocturnal pulse oximetry and home nocturnal cough recording in young children with CF, and determine whether these tests can distinguish CF patients from healthy controls. METHODS: We performed a prospective cross-sectional study in 20 CF patients and 30 healthy children aged 0-4 years. MBW was performed in awake and unsedated children at the outpatient clinic using a commercially available device. Measurements of nocturnal oxygen saturation and nocturnal cough were done at home using a pulse oximeter and an audiometer. RESULTS: There was a significant difference in mean LCI between healthy children and CF patients (LCI 7.1 vs. 9.3, p<0.001). Nocturnal oxygen saturation was normal in both groups and did not significantly differ between the groups. Similarly, cough showed no differences between both groups. Cough varied widely between children and between nights. Success rates for saturation and cough measurements were 90% and were similar for CF patients and healthy children. Success rate for LCI was 75% for CF patients and 50% for healthy children. CONCLUSIONS: Measurements of LCI, nocturnal oxygen saturation and cough were feasible in young children; however LCI was the only variable that showed a significant difference between children with CF and healthy children.

Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation.

Better treatment of obstructed small airways is needed in cystic fibrosis. This study investigated whether efficient deposition of dornase alfa in the small airways improves small airway obstruction. In a multicentre, double-blind, randomised controlled clinical trial, cystic fibrosis patients on maintenance treatment with 2.5 mL dornase alfa once daily were switched to a smart nebuliser and randomised to small airway deposition (n = 24) or large airway deposition (n = 25) for 4 weeks. The primary outcome parameter was forced expiratory flow at 75% of forced vital capacity (FEF(75%)). FEF(75%) increased significantly by 0.7 sd (5.2% predicted) in the large airways group and 1.2 sd (8.8% pred) in the small airways group. Intention-to-treat analysis did not show a significant difference in treatment effect between groups. Per-protocol analysis, excluding patients not completing the trial or with adherence <70%, showed a trend (p = 0.06) in FEF(75%) Z-score and a significant difference (p = 0.04) between groups in absolute FEF(75%) (L · s(-1)) favouring small airway deposition. Improved delivery of dornase alfa using a smart nebuliser that aids patients in correct inhalation technique resulted in significant improvement of FEF(75%) in children with stable cystic fibrosis. Adherent children showed a larger treatment response for small airway deposition.

Ultrasonographic tissue characterisation of human Achilles tendons: quantification of tendon structure through a novel non-invasive approach.

OBJECTIVE: To assess whether three-dimensional imaging of the Achilles tendon by ultrasonographic tissue characterisation (UTC) can differentiate between symptomatic and asymptomatic tendons. DESIGN: Case-control study. SETTING: Sports Medical Department of the Hague Medical Centre. PATIENTS: Twenty-six tendons from patients with chronic midportion Achilles tendinopathy were included. The "matched" control group consisted of 26 asymptomatic tendons. INTERVENTIONS: Symptomatic and asymptomatic tendons were scanned using the UTC procedure. One researcher performed the ultrasonographic data collection. These blinded data were randomised, and outcome measures were determined by two independent observers. MAIN OUTCOME MEASUREMENTS: The raw ultrasonographic images were analysed with a custom-designed algorithm that quantifies the three-dimensional stability of echo patterns, qua intensity and distribution over contiguous transverse images. This three-dimensional stability was related to tendon structure in previous studies. UTC categorises four different echotypes that represent (I) highly stable; (II) medium stable; (III) highly variable and (IV) constantly low intensity and variable distribution. The percentages of echo-types were calculated, and the maximum tendon thickness was measured. Finally, the inter-observer reliability of UTC was determined. RESULTS: Symptomatic tendons showed less pixels in echo-types I and II than asymptomatic tendons (51.5% vs 76.6%, p<0.001), thus less three-dimensional stability of the echo pattern. The mean maximum tendon thickness was 9.2 mm in the symptomatic group and 6.8 mm in the asymptomatic group (p<0.001). The Intraclass Correlation Coefficient (ICC) for the interobserver reliability of determining the echo-types I+II was 0.95. The ICC for tendon thickness was 0.84. CONCLUSION: UTC can quantitatively evaluate tendon structure and thereby discriminate symptomatic and asymptomatic tendons. As such, UTC might be useful to monitor treatment protocols.

Pharmacology, clinical efficacy and safety of recombinant human DNase in cystic fibrosis.

Recombinant human DNase (rhDNase) is a mucolytic agent that is primarily used to improve mucociliary clearance in cystic fibrosis (CF). rhDNase is a recombinant human enzyme that is synthesized in a Chinese hamster ovary cell line. rhDNase enzymatically cleaves extracellular DNA into molecules of shorter length. CF sputum shows high concentrations of DNA released by disintegrating inflammatory cells. Free DNA contributes to the abnormally high viscosity of CF sputum and therefore forms an important target in the treatment of CF lung disease. Clinical studies have shown that daily nebulization of rhDNase is associated with an increase in lung function and a decrease in the frequency of exacerbations in patients with CF.

High fractional concentration of nitric oxide in exhaled air despite steroid treatment in asthmatic children.

BACKGROUND: The fractional concentration of nitric oxide in exhaled air (FENO) is elevated in atopic asthma and typically responds to treatment with inhaled corticosteroids (ICS). However, some patients have persistently high FENO levels despite treatment. OBJECTIVE: We studied how optimizing the inhalation technique and increasing ICS doses would affect FENO in stable atopic asthmatic children who had elevated FENO while using ICS. METHODS: In 41 stable asthmatic children who were treated with ICS (median daily dose 800 microg budesonide equivalent, range 100-1600 microg) and maintained FENO> or =20 p.p.b., we optimized the inhalation technique by thorough instruction and measured FENO 2 weeks later. Then, if FENO remained > or =20 p.p.b., we increased the ICS dose and reassessed FENO 2 weeks later. RESULTS: Improving the inhalation technique did not reduce FENO. Increasing ICS from a daily median dose of 800 to 1200 microg budesonide had no significant effect on FENO. FENO correlated positively with symptom scores in the following 2 and 4 weeks (P=0.001, 0.002) and beta2-agonist use the 2 and 4 weeks following FENO measurement (P=0.02, 0.004). CONCLUSION: We conclude that common steps in asthma treatment, i.e. inhalation instruction and increasing ICS dose, were both ineffective in reducing FENO in atopic asthmatic children with elevated FENO values despite treatment with ICS. This implies that FENO cannot simply be incorporated in current treatment guidelines.

Unlicensed and off-label drug use in a paediatric ward of a general hospital in the Netherlands.

OBJECTIVES: Many drugs used in paediatric care are not licensed for that use or are prescribed outside the terms of the product license (off-label). Studies in the UK and Europe showed a large number of unlicensed and off-label drug prescription in specialised paediatric health care centres. We determined the extent and nature of use of unlicensed drugs and off-label prescriptions in children in a general hospital in the Netherlands. METHODS: We conducted a longitudinal prospective cohort study in a dynamic population consisting of patients admitted to the paediatric ward and the neonatology unit of a general hospital during a 19-week period. Drug-licensing status of all prescriptions given to these patients was determined. RESULTS: A total of 1017 prescriptions was administered to 293 paediatric patients for 114 different drugs. The median number of prescriptions per patient was three (interquartile range 2-5). The most commonly administered drugs were acetaminophen (14%), cefotaxime (8%), amoxicillin (7%), caffeine (4%) and prednisolone (4%). Four hundred and forty-three (44%) prescriptions were off-label, and 285 (28%) were for unlicensed drugs. Ninety-two percent of patients received one or more unlicensed or off-label prescriptions, and this proportion was significantly higher in children below 6 months of age than in older children. CONCLUSIONS: This study shows that the extent of unlicensed and off-label drug prescription in a paediatric ward and neonatology unit of a general hospital is large and not smaller than in an academic paediatric setting. Lack of paediatric drug labelling is therefore not solely a problem with drugs used in university hospitals, but also in general hospitals. Efforts must be taken to change the current situation.

Efficacy of computerized discrimination between structure-related and non-structure-related echoes in ultrasonographic images for the quantitative evaluation of the structural integrity of superficial digital flexor tendons in horses.

OBJECTIVE: To evaluate effectiveness of computerized discrimination between structure-related and non-structure-related echoes in ultrasonographic images for quantitative evaluation of tendon structural integrity in horses. SAMPLE POPULATION: 4 superficial digital flexor tendons (2 damaged tendons, 2 normal tendons). PROCEDURE: Transverse ultrasonographic images that precisely matched histologic sections were obtained in fixed steps along the long axis of each tendon. Distribution, intensity, and delineation of structure-related echoes, quantitatively expressed as the correlation ratio and steadiness ratio , were compared with histologic findings in tissue that was normal or had necrosis, early granulation, late granulation, early fibrosis, or inferior repair. RESULTS: In normal tendon, the even distribution of structure-related echoes with high intensity and sharp delineation yielded high correlation ratio and steadiness ratio. In areas of necrosis, collapsed endotendon septa yielded solid but blurred structure-related echoes (high correlation ration and low steadiness ratio). In early granulation tissue, complete lack of organization caused zero values for both ratios. In late granulation tissue, reorganization and swollen endotendon septa yielded poorly delineated structure-related echoes (high correlation ratio, low steadiness ratio). In early fibrosis, rearrangement of bundles resulted in normal correlation ration and slightly low steadiness ratio. In inferior repair, the almost complete lack of structural reorganization resulted in heterogeneous poorly delineated low-intensity echoes (low correlation ratio and steadiness ratio). CONCLUSIONS AND CLINICAL RELEVANCE: The combination of correlation ratio and steadiness ratio accurately reflects histopathologic findings, making computerized correlation of ultrasonographic images an efficient tool for quantitative evaluation of tendon structural integrity.

Structure-related echoes in ultrasonographic images of equine superficial digital flexor tendons.

OBJECTIVE: To develop a method to discriminate between structure-related echoes and echoes resulting from interference, as observed in transverse ultrasonographic images of equine superficial digital flexor (SDF) tendons. SAMPLE POPULATION: 2 normal (injury-free) SDF tendons obtained from a 3-year-old Thoroughbred and a 9-year-old Dutch Warmblood horse. PROCEDURE: Tendons were mounted in a custom-made device that permitted exact transverse and perpendicular sequential scanning with precise steps of 0.5 mm along the long axis of the tendon. Photographs of transverse tendon sections at the exact scanning locations were obtained. Propagation, reflection, and refraction artifacts were quantified, and an image rectification procedure was developed, allowing exact matching of each photograph with the corresponding ultrasonographic image. A correlation routine was developed that departed from this transverse ultrasonographic image (position 0); this routine added information from images collected at precise distances of 0.5 and 1 mm on both sides of the actual scan location (positions -2, -1, +1, +2). RESULTS: By use of the correlation routine, echoes that remained steady over all 5 images were enhanced and resolved, and constantly changing echoes were multiplicatively reduced and faded. This correlated image could be projected over the rectified photograph, and the resolved echoes matched perfectly with the endotendon septa surrounding fibers and fasciculi. CONCLUSIONS AND CLINICAL RELEVANCE: The correlation routine permits exclusive resolution of structure-related echoes, as echoes resulting from interference are faded. The technique described can produce images that depict only the essential structure-related information. In this way, the clinical assessment of tendon integrity is greatly facilitated.

Ultrasonographic tissue characterization of equine superficial digital flexor tendons by means of gray level statistics.

OBJECTIVE: To correlate quantitative analysis of ultrasonographic images of normal (injury-free) equine superficial digital flexor (SDF) tendons and equine SFD tendons that have pathologic changes with corresponding histologic sections. SAMPLE POPULATION: 4 SDF tendons, 2 of which had various stages of tissue integrity. The 2 ipsilateral tendons were used as points of reference. PROCEDURE: Tendons were mounted in a custom-made device that permitted sequential scanning, transversely and perpendicular to the tendon long axis. At precise steps of 0.5 mm, transverse ultrasonographic images were collected. Subsequently, tendons were fixed and prepared for histologic examination. The following 8 tissue types were discerned: normal young, normal old, necrotic, early granulation, late granulation, early fibrotic, late fibrotic, and scar tissues. In areas of interest, the corresponding ultrasonographic images were selected for gray level statistical analysis. RESULTS: Compared with other tissue types, early-stage granulation tissue was characterized by substantially lower mean gray level and a clearly different histogram. Necrotic tissue had a higher mean gray level, with a virtually normal histogram. In late granulation and early fibrotic tissues, the mean gray level and the histogram could not be discerned from those of normal tendon tissue. The same applied to late fibrotic and scar tissues; mean gray levels were fractionally lower than those of normal tendon tissue with a completely normal histogram. CONCLUSIONS: Although quantification of the transverse ultrasonographic image by use of first-order gray level statistics may be helpful, the method is not sufficiently sensitive to accurately and unequivocally determine the type of tendon tissue. Quantitative analysis should incorporate transverse and longitudinal information.

Ultrasonographic evaluation of equine tendons: a quantitative in vitro study of the effects of amplifier gain level, transducer-tilt, and transducer-displacement.

The objective of the in vitro experiments described in this paper was to quantify the effects of some instrumental variables on the quantitative evaluation, by means of first-order gray-level statistics, of ultrasonographic images of equine tendons. The experiments were done on three isolated equine superficial digital flexor tendons that were mounted in a frame and submerged in a waterbath. Sections with either normal tendon tissue, an acute lesion, or a chronic scar, were selected. In these sections, the following experiments were done: 1) a gradual increase of total amplifier gain output subdivided in 12 equal steps; 2) a transducer tilt plus or minus 3 degrees from perpendicular, with steps of 1 degree; and 3) a transducer displacement along, and perpendicular to, the tendon long axis, with 16 steps of 0.25 mm each. Transverse ultrasonographic images were collected, and in the regions of interest (ROI) first-order gray-level statistics were calculated to quantify the effects of each experiment. Some important observations were: 1) the total amplifier gain output has a substantial influence on the ultrasonographic image; for example, in the case of an acute lesion, a low gain setting results in an almost completely black image; whereas, with higher gain settings, a marked "filling in" effect on the lesion can be observed; 2) the relative effects of the tilting of the transducer are substantial in normal tendon tissue (18%) and chronic scar (12%); whereas, in the event of an acute lesion, the effects on the mean gray level are dramatic (40%); and 3) the relative effects of displacement of the transducer are small in normal tendon tissue, but on the other hand, the mean gray-level changes 7% in chronic scar, and even 20% in an acute lesion. In general, slight variations in scanner settings and transducer handling can have considerable effects on the gray levels of the ultrasonographic image. Furthermore, there is a strong indication that this quantitative method, as far as based exclusively on the first-order gray-level statistics, may be not discriminative enough to accurately assess the integrity of the tendon. Therefore, the value of a quantitative evaluation of the first-order gray-level statistics for the assessment of the integrity of the equine tendon is questionable.