Perception, experience and relationship with food and eating in adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disorder that primarily affects the respiratory and gastrointestinal systems. Dietetic therapy is a prominent aspect of CF management, with patients receiving nutritional surveillance and advice throughout their lifetime. The present study aimed to explore the perception, experience and relationship with food and eating in adults with CF. METHODS: Semi-structured telephone interviews were conducted with nine adults with CF. Interviews were audio-recorded, transcribed verbatim and analysed thematically following a previously described six-phase procedure. RESULTS: Six themes were identified: 'Sustained influence of eating experience in childhood', 'Eating for health: weight gain to prevent infection', 'Balancing health and body image', 'I'm different,' 'Strategies for managing food intake' and 'Support from family, friends and the CF Team'. Participants talked about the range of strategies they employ, with a focus on eating well and choosing high calorie foods being an important part of their health management strategy. This is driven by the belief that a good weight ensures better health and perceiving eating as a treatment. CONCLUSIONS: This group felt able to cope well and had developed strategies to manage their dietary needs. Food experience was variable throughout their lifetime, with childhood experience having a sustained effect on adult eating behaviour. Weight gain, body image and dietary health implications are considerable concerns for patients. New CF transmembrane modulator treatments (CFTR modulators) are changing the dietary needs of this population. It is important that these issues are explored during dietetic consultations to identify barriers to dietary change.

Vitamin E supplementation in people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency, including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended for people with cystic fibrosis and aims to ameliorate this deficiency. This is an updated version of the review. OBJECTIVES: To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international online trial registries for any ongoing clinical trials that were not identified during our register search. Date of last search of the Register: 11 August 2020. Date of last search of international online trial registries: 20 July 2020. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. DATA COLLECTION AND ANALYSIS: Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. They assessed the quality of the evidence using GRADE. MAIN RESULTS: Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo. There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. None of the studies in either comparison report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Water-soluble vitamin E Water-soluble vitamin E may improve serum vitamin E levels compared with control at six months, one study (45 participants), mean difference (MD) 19.74 umol/L (95% confidence interval (CI) 13.48 to 26.00) (low-quality evidence). Similar results were also seen at one month, two studies (32 participants), MD 17.66 umol/L (95% CI 10.59 to 24.74) and at three months, one study (45 participants), MD 11.61 umol/L (95% CI 4.77 to 18.45). Only one study (45 participants) reported weight (secondary outcome of growth and nutritional status) at one and six months, but showed no difference between treatment and control at either time point. Fat-soluble vitamin E Two studies (36 participants) reported higher levels of serum vitamin E at one month with fat-soluble vitamin E compared with control, MD 13.59 umol/L (95% CI 9.52 to 17.66); however, at three months one study (36 participants) showed no difference between treatment and control. No studies in this comparison reported on growth or nutritional status. AUTHORS' CONCLUSIONS: Vitamin E supplementation may lead to an improvement in vitamin E levels in people with cystic fibrosis, although evidence we assessed was low quality. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy. In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Vitamin E supplementation in people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended in cystic fibrosis and aims to ameliorate this deficiency. This is an updated version of the review. OBJECTIVES: To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international trial registers for any ongoing clinical trials that were not identified during our register search.Date of last search of the Register: 10 October 2016. Date of last search of international trial registers: 15 February 2017. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. DATA COLLECTION AND ANALYSIS: Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. MAIN RESULTS: Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and the other two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo.At one month, three months and six months, water-soluble vitamin E significantly improved serum vitamin E levels compared with control: at one month, two studies, mean difference 17.66 (95% confidence interval 10.59 to 24.74); at three months, one study, mean difference 11.61 (95% confidence interval 4.77 to 18.45); and at six months, one study, mean difference 19.74 (95% confidence interval 13.48 to 26.00). At one month fat-soluble vitamin E significantly improved serum vitamin E levels compared with control: one month, two studies, mean difference 13.59 (95% CI 9.52 to 17.66). The findings at three months were imprecise; one study; mean difference 6.40 (95% confidence interval -1.45 to 14.25).None of the studies report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Only one study, comparing water-soluble vitamin E with placebo, reported the secondary outcome of growth and nutritional status (weight), but the results are uncertain due to imprecision around the effect estimate.There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. AUTHORS' CONCLUSIONS: Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Physical activity in adults with cystic fibrosis receiving intravenous antibiotics in hospital and in the community.

INTRODUCTION: Intravenous antibiotic therapy (IVAT) for CF acute pulmonary exacerbations (APE) can be delivered in hospital or in the community. This study aimed to compare physical activity in CF patients receiving hospital and community-delivered IVAT, as well as other health outcomes. MATERIALS AND METHODS: This was a non-randomised parallel group prospective observational study. Hospitalised and community-treated CF adults receiving IVAT for APE were asked to wear ActiGraph® activity monitors, complete the habitual activity estimation scale (HAES), food diary, modified shuttle test (MST) and CFQ-R at the start and end of therapy. Nutritional and clinical outcomes were also compared between the cohorts. The primary outcomes was physical activity measured by the ActiGraph® activity monitors at the beginning and end of treatment in both cohorts. RESULTS: Physical activity (measured and self-reported) was no different between the cohorts, with both hospitalised and community-treated subjects being generally sedentary. Body weight increased significantly in the hospitalised cohort, whereas no difference was seen in the community-treated cohort. FEV1 % predicted and FVC % predicted increased in community-treated subjects, whereas only FVC % predicted increased in hospitalised subjects. CFQ-R respiratory domain increased to a greater extent in community-treated subjects. CONCLUSION: CF adults receiving IVAT for APE, both in hospital and in the community, are generally sedentary and we found no difference in physical activity between the two groups. These findings suggests the need to further promote physical activity in suitable patients during APE where considered appropriate.

Vitamin E supplementation in people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended in cystic fibrosis and aims to ameliorate this deficiency. OBJECTIVES: To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international trial registers for any ongoing clinical trials that were not identified during our register search.Date of last search of the Register: 10 February 2014. Date of last search of international trial registers: 30 August 2014. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. DATA COLLECTION AND ANALYSIS: Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. MAIN RESULTS: Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and the other two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo.At one month, three months and six months, water-soluble vitamin E significantly improved serum vitamin E levels compared with control: at one month, two studies, mean difference 17.66 (95% confidence interval 10.59 to 24.74); at three months, one study, mean difference 11.61 (95% confidence interval 4.77 to 18.45); and at six months, one study, mean difference 19.74 (95% confidence interval 13.48 to 26.00). At one month fat-soluble vitamin E significantly improved serum vitamin E levels compared with control: one month, two studies, mean difference 13.59 (95% CI 9.52 to 17.66). The findings at three months were imprecise; one study; mean difference 6.40 (95% CI -1.45 to 14.25).None of the studies report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Only one study, comparing water-soluble vitamin E with placebo, reported the secondary outcome of growth and nutritional status (weight), but the results are uncertain due to imprecision around the effect estimate.There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. AUTHORS' CONCLUSIONS: Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

The safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of RO5068760, an MEK inhibitor, in healthy volunteers: assessment of target suppression.

RO5068760, a substituted hydantoin, represents a new class of potent, highly selective, non-adenosine triphosphate (ATP)-competitive MEK1/2 inhibitors. The study aimed to determine the safety/tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of RO5068760 in human healthy volunteers. All participants received a single dose followed by 48 hours of pharmacokinetics, pharmacodynamics, and safety/tolerability assessments. The pharmacodynamics were measured by changes in ERK phosphorylation (pERK) in peripheral blood mononuclear cells, ex vivo stimulated by phorbol 12-myristate 13-acetate (PMA). Forty-eight participants received 6 doses (50, 100, 200, 400, 600, 800 mg). RO5068760 was well tolerated up to 800 mg. There were no clinically significant safety findings, including laboratory, electrocardiogram, ophthalmological assessment, and fecal occult blood tests. Of the total 13 adverse events (n = 12), 11 were mild, 2 were moderate, and none were severe, and only 5 were considered by the investigator as possibly related to treatment. RO5068760 was absorbed with a t(max), of 2 hours. Disposition appeared to be biphasic with a terminal elimination t(1/2) of 5 to 9 hours. The variability was moderate to high, ranging from 38% to 62% for C(max) and 41% to 69% AUC. Within the dose range tested, pERK inhibition was relatively modest with a mean maximal pERK suppression of 55%.

The safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of CH4987655 in healthy volunteers: target suppression using a biomarker.

PURPOSE: CH4987655 (RO4987655) is an orally active and highly selective small-molecule MEK inhibitor. It potently inhibits mitogen-activated protein kinase signaling pathway activation and tumor cell growth, with an in vitro IC(50) of 5.2 nmol/L for inhibition of MEK1/2. Single-agent oral administration of CH4987655 resulted in complete tumor regressions in xenograft models. EXPERIMENTAL DESIGN: All 40 subjects received a single oral dose followed by 72 hrs of pharmacokinetic, pharmacodynamic, and safety/tolerability assessments. The pharmacodynamics were measured by changes in phosphorylated extracellular signal-regulated kinase (pERK) levels in a surrogate tissue peripheral blood mononuclear cells ex vivo stimulated by PMA. RESULTS: Doses of 0.5, 1, 2, 3, and 4 mg were safe and well tolerated. No clinically significant safety event was observed. A total of 26 adverse events (n = 15) were reported: 21 mild, 5 moderate, and none severe. Moderate adverse events were experienced by one subject at 1 mg (autonomic nervous system imbalance) and three subjects at 4 mg (diarrhea, abdominal pain, autonomic nervous system and acne). CH4987655 was rapidly absorbed with a t(max) of approximately 1 h. Exposures were dose proportional from 0.5 to 4 mg. The disposition was biphasic with a terminal t(1/2) of approximately 25 hr. Intersubject variability was low, 9% to 23% for C(max) and 14% to 25% for area-under-the-curve (AUC). pERK inhibition was exposure dependent and was greater than 80% inhibition at higher doses. The pharmacokinetic-pharmacodynamic relationship was characterized by an inhibitory E(max) model (E(max) approximately 100%; IC(50) 40.6 ng/mL) using nonlinear mixed-effect modeling. CONCLUSIONS: A significant extent of pERK inhibition was achieved for a single dose that was considered to be safe and well tolerated in healthy volunteers.

Monthly oral ibandronate is well tolerated and efficacious in postmenopausal women: results from the monthly oral pilot study.

CONTEXT: Ibandronate, a potent, nitrogen-containing bisphosphonate developed for intermittent administration in postmenopausal osteoporosis, aims to overcome current adherence issues with daily and weekly oral bisphosphonates through once-monthly oral dosing. OBJECTIVE: The purpose of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of once-monthly oral ibandronate. DESIGN: A randomized, 3-month, double-blind, placebo-controlled, phase I study (Monthly Oral Pilot Study) was conducted. SETTING: The study was conducted at five clinical trial centers in the United Kingdom and Belgium. PATIENTS OR OTHER PARTICIPANTS: Subjects were postmenopausal women (age, 55-80 yr; > or =3 yr post menopause; n = 144). INTERVENTION(S): Once-monthly oral ibandronate 50, 100, or 150 mg or placebo was used. After the first cycle, the 50-mg arm was split, with participants continuing on either 50 or 100 mg. MAIN OUTCOME MEASURE(S): Primary outcome measures were safety, serum and urinary C-telopeptide (CTX), and serum ibandronate AUC0-infinity. RESULTS: Once-monthly oral ibandronate was well tolerated, with a similar overall and upper gastrointestinal safety profile to placebo. Once-monthly ibandronate was also highly effective in decreasing bone turnover; substantial reductions from baseline in serum CTX (-56.7% and -40.7% in the 150- and 100-mg arms, respectively; P < 0.001 vs. placebo) and urinary CTX (-54.1% and -34.6%, respectively; P < 0.001 vs. placebo) were observed at d 91 (30 d after the final dose). Analysis of the area under the effect curve (d 1-91) for change from baseline (percent x days) in serum CTX and urinary CTX indicated a dose-response relationship. The AUC0-infinity for ibandronate increased with dose but not in a dose-proportional manner. CONCLUSIONS: These findings indicate a potential role for once-monthly oral ibandronate in the treatment of postmenopausal osteoporosis.

Ibandronate: a clinical pharmacological and pharmacokinetic update.

Ibandronate is a potent nitrogen-containing bisphosphonate. It has a strong affinity for bone mineral and potently inhibits osteoclast-mediated bone resorption. Ibandronate is effective for the treatment of hypercalcemia of malignancy, metastatic bone disease, postmenopausal osteoporosis, corticosteroid-induced osteoporosis, and Paget's disease. Oral ibandronate is rapidly absorbed (t(max) < 1 hour), with a low bioavailability (0.63%) that is further reduced (by up to 90%) in the presence of food. Ibandronate has a wide therapeutic index and is not metabolized and, therefore, has a low potential for drug interactions. Given its metabolic stability, ibandronate is eliminated from the blood by partitioning into bone (40%-50%) and through renal clearance (CL(R) approximately 60 mL/min). The CL(R) of ibandronate is linearly related to creatinine clearance. The sequestration of ibandronate in bone (V(D) > 90 L) results in a multiphasic elimination (t((1/2)) range approximately 10-60 hours), characterized by the slow release of ibandronate from the bone compartment. The potency of ibandronate and its sequestration into bone allow ibandronate to be developed as oral and intravenous injection formulations that can be administered with convenient extended between-dose intervals.