Body composition and weight changes after ivacaftor treatment in adults with cystic fibrosis carrying the G551 D cystic fibrosis transmembrane conductance regulator mutation: A double-blind, placebo-controlled, randomized, crossover study with open-label extension.

OBJECTIVES: In patients with cystic fibrosis (CF) who carry the G551D mutation, treatment with ivacaftor improves lung function and weight; however, short- and long-term impacts on body composition have not been well studied. METHODS: Twenty adults with CF carrying the G551D mutation (mean ± standard deviation body mass index [BMI] 23.3 ± 4.3 kg/m2) were recruited for a single-center, double-blind, placebo-controlled, 28-d, crossover study of ivacaftor, followed by an open-label extension (OLE) for 5 mo. Eleven patients underwent measurements 2 y later. The study variables included weight, BMI, and body composition (including fat-free mass [FFM] and fat mass). RESULTS: After 28 d of treatment with ivacaftor, weight increased by 1.1 ± 1.3 kg, BMI by 0.4 ± 0.5 kg/m2, and FFM by 1.1 ± 1.2 kg (all P < .005) with no change in fat mass. Differences between 28-d changes on ivacaftor and placebo were not statistically significant. In the following 5 mo of the OLE, there were significant increases in weight (1.2 ± 1.9 kg; P < .05) and fat mass (1.5 ± 1.9 kg; P < .01), but not in FFM. Between baseline and the end of the OLE, the total weight gain was 2.5 ± 2.4 kg (P < .005), comprised of 0.9 ± 1.5 kg FFM (P < .05) and 1.6 ± 1.8 kg fat mass (P < .005). For the 11 participants who were followed for a further 2 y, no further changes in mean weight, BMI, or body composition parameters between 6 mo and 2 y later were observed. CONCLUSIONS: Small gains were seen in FFM in the first month of ivacaftor treatment. Weight, BMI, and fat-mass gains in the first 6 mo on ivacaftor plateaued by 2.5 y. The metabolic and clinical consequences of weight and fat-mass gains remain to be determined.

Patient's perceptions of physical examination in the setting of chronic pain.

INTRODUCTION: Despite its clinical utility, progressive reliance on imaging technology can lead to devaluing the physical examination in patients with chronic pain. The primary objective of this study was to determine whether chronic pain patients have a positive or negative perception of the physical examination. METHODS: After institutional ethics committee approval, 120 adult patients as a convenience sample who attended a chronic pain clinic were included. Participants completed a 10-item survey regarding their overall perception of the physical examination. Kruskal-Wallis and Mann-Whitney U test analyses were conducted to explore associations between test items and patient ages, gender, employment, pain diagnosis, and duration of pain. All cross-tabulations of categorical variables were analyzed using Fisher's exact test for associations. RESULTS: The majority of participants were male (51%), aged 50-70 (44%). The most common pain diagnosis was back pain (62%). Most patients (77%) indicated that the overall experience of being examined was highly positive. Patients believe in the value of the physical examination as a diagnostic tool (97%). Patients believe in the relational value of the physical examination (92%). Age, gender, employment, pain diagnosis, and duration of pain were not associated with a more positive perception of the physical examination. CONCLUSION: Patients with chronic pain indicate that the physical examination is a highly positive aspect of their care. There are some negative aspects of been examined which physicians should be aware of. This study adds to our knowledge regarding the physical exam in chronic pain patients. It will inform practice and training.

Attitudes of Irish patients with chronic pain towards medicinal cannabis.

BACKGROUND: Medicinal cannabis use is topical in the media in Ireland. A recent Health Products Regulatory Authority review, however, has recommended against its use for patients with chronic pain. This is despite evidence for its effectiveness in this patient's cohort and the inadequate pain management of these patients. AIM: The aim of this study was to evaluate the attitudes of Irish patients with chronic pain towards medicinal cannabis. METHODS: After institutional ethics committee approval, a 12-item questionnaire (excluding demographics) was randomly assigned to patients attending a chronic pain clinic (University Hospital Limerick). The questionnaire was designed to incorporate patient's attitudes on a variety of medicinal cannabis related topics. RESULTS: Ninety-six adult patients were surveyed. 88.54% agreed that cannabis should be legalised for chronic pain medicinal purposes. 80.21% believed it would have health benefits for them and 73.96% agreed it would be socially acceptable to use cannabis for this purpose. 33.33% perceived cannabis to be addictive while 68.75% would be willing to try it if prescribed by a medical professional. CONCLUSIONS: The study highlights the attitudes of chronic pain patients in Ireland towards medicinal cannabis. It shows their desire to have medical cannabis legalised for chronic pain and that they view it as a reasonable pain management option.

Antibiotic exposure and interpersonal variance mask the effect of ivacaftor on respiratory microbiota composition.

BACKGROUND: G551D is a class III mutation of the cystic fibrosis transmembrane regulator (CFTR) that results in impaired chloride channel function in cystic fibrosis (CF). Ivacaftor, a CFTR-potentiating agent improves sweat chloride, weight, lung function, and pulmonary exacerbation rate in CF patients with G551D mutations, but its effect on the airway microbiome remains poorly characterised. METHODS: Twenty CF patients with at least one G551D mutation from a single centre were recruited to a 4month double-blind, placebo-controlled, crossover study of ivacaftor with 28days of active treatment. Sputum microbiota composition was assessed by 16S rRNA gene amplicon sequencing and quantitative PCR at five key time points, along with regular clinical review, respiratory function assessment, and peripheral blood testing. RESULTS: No significant difference in microbiota composition was observed in subjects following ivacaftor treatment or placebo (PERMANOVA P=0.95, square root ECV=-4.94, 9479 permutations). Microbiota composition variance was significantly greater between subjects, than within subjects over time (P<0.0001, Mann Whitney U test), and an additional within-patient paired assessment of microbiota similarity was therefore performed. Again, change in microbiota composition was not significantly greater during treatment with ivacaftor compared to placebo (Wilcoxon test, P=0.51). A significant change in microbiota composition was however associated with any change in antibiotic exposure, regardless of whether ivacaftor or placebo was administered (P=0.006). In a small, subgroup analysis of subjects whose antibiotic exposure did not change within the study period, a significant reduction in total bacterial load was observed during treatment with ivacaftor (P=0.004, two-tailed paired Student's t-test). CONCLUSIONS: The short-term impact of ivacaftor therapy on sputum microbiota composition in patients with G551D mutations are modest compared to those resulting from antibiotic exposure, and may be masked by changes in antibiotic treatment regimen.

Improvement in exercise duration, lung function and well-being in G551D-cystic fibrosis patients: a double-blind, placebo-controlled, randomized, cross-over study with ivacaftor treatment.

G551D, a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, results in impaired chloride channel function in cystic fibrosis (CF) with multiple end-organ manifestations. The effect of ivacaftor, a CFTR-potentiator, on exercise capacity in CF is unknown. Twenty G551D-CF patients were recruited to a single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor. Variables measured included percentage change from baseline (%Δ) of VO2max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiological variables, lung function, body mass index (BMI), sweat chloride and disease-specific health related quality of life (QOL) measures (CFQ-R and Alfred Wellness (AWEscore)). %ΔVO2max was unchanged compared with placebo as was %Δminute ventilation. However, %Δexercise time (mean 7.3, CI 0.5-14,1, P=0.0222) significantly increased as did %ΔFEV1 (11.7%, range 5.3-18.1, P<0·005) and %ΔBMI (1.2%, range 0.1-2.3, P=0·0393) whereas sweat chloride decreased (mean -43.4; range -55.5-18.1 mmol·l-1, P<0·005). Total and activity based domains in both CFQ-R and AWEscore also increased. A positive treatment effect on spirometry, BMI (increased), SCT (decreased) and total and activity based CF-specific QOL measures was expected. However, the lack of discernible improvement in VO2max and VE despite other positive changes including spirometric lung function and exercise time with a 28-day ivacaftor intervention suggests that ventilatory parameters are not the sole driver of change in exercise capacity in this study cohort. Investigation over a more prolonged period may delineate the potential interdependencies of the observed discordances over time. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov-NCT01937325.