Background: People with cystic fibrosis (CF) can experience recurrent chest infections, pancreatic exocrine insufficiency and gastrointestinal symptoms. New cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs improve lung function but gastrointestinal effects are unclear. We aimed to see if a CFTR modulator (tezacaftor-ivacaftor,TEZ/IVA) improves gastrointestinal outcomes in CF.
Methods: We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (2019-2020) at Nottingham University Hospitals. The effects of TEZ/IVA on gut physiology were measured using MRI. Participants were randomly assigned to treatment sequences AB or BA (A:TEZ/IVA, B:placebo, each 28 days), with a 28-day washout period. Participants had serial MRI scans at baseline and after 19-23 days of each treatment. Due to the COVID-19 pandemic, a protocol amendment allowed for observer-blind comparisons prior to and during TEZ/IVA. In such cases, participants were not blind to the treatment but researchers remained blind. The primary outcome was oro-caecal transit time (OCTT). Secondary outcomes included MRI metrics, symptoms and stool biomarkers.
Results: We randomised 13 participants. Before the COVID-19 pandemic 8 participants completed the full protocol and 1 dropped out. The remaining 4 participants followed the amended protocol. There were no significant differences between placebo and TEZ/IVA for OCTT (TEZ/IVA >360minutes [225,>360] vs. placebo 330minutes [285,>360], p=0.8) or secondary outcomes. There were no adverse events.
Conclusions: Our data contribute to a research gap in the extra-pulmonary effects of CFTR modulators. We found no effect after TEZ/IVA on MRI metrics of gut function, GI symptoms or stool calprotectin. Effects might be detectable with larger studies, longer treatment or more effective CFTR modulators.
Clinicaltrialsgov registration: NCT04006873 (02/07/2019).
Frailty describes a health state related to ageing where people become less resilient to health challenges and more likely to have adverse outcomes if they become unwell. People experiencing homelessness (PEH) are known to have poor health, with research suggesting that many become frail at a younger age than the general population. Previous research using small-scale primary data collection suggests that the prevalence of frailty in homeless populations varies widely (16-55%), with variations in sample sizes and settings partially accounting for differences in current estimates. The prevalence, risks, and outcomes of frailty in PEH are poorly understood. We propose to carry out a secondary analysis of existing health survey data collected from 2,792 PEH. This will involve creating a Frailty Index (FI) to identify frail people within the dataset. Regression analyses will be used to identify associations between potential risk factors and outcomes of frailty in this population. This protocol will: 1) Outline the creation of a FI to assess the frailty prevalence within a dataset of health information collected from a cohort of PEH and 2) Describe proposed methods of regression analysis for identification of associations between frailty and risks factors/outcomes of frailty in the cohort of PEH within the dataset. The processes described in this paper can inform future development of FIs in other datasets. It is expected that the FI created will be an appropriate and robust method for identifying frailty in a cohort of PEH and results of the secondary data analysis will provide a more robust estimate of the associations between frailty and risk factors/outcomes.
Background: The persistence of symptoms for ≥12 weeks after a COVID-19 infection is known as Long COVID (LC), a condition with unclear pathophysiology and no proven treatments to date. Living with obesity is a risk factor for LC and has symptoms which may overlap with and aggravate LC.
Methods: ReDIRECT is a remotely delivered trial assessing whether weight management can reduce LC symptoms. We recruited people with LC and BMI >27kg/m 2. The intervention was delivered remotely by dietitians, with online data collection (medical and dietary history, COVID-19 infection and vaccination, body composition, LC history/symptoms, blood pressure, quality of life, sociodemographic data). Participants self-selected the dominant LC symptoms they most wanted to improve from the intervention.
Results: Participants (n=234) in England (64%) and Scotland (30%) were mainly women (85%) of white ethnicity (90%), with 13% living in the 20% most deprived areas, a mean age of 46 (SD10) years, and median BMI of 35kg/m 2 (IQR 32-40). Before starting the study, 30% reported more than one COVID-19 infection (82% confirmed with one or more positive tests). LC Diagnosis was mainly by GPs (71%), other healthcare professionals (9%), or self-diagnosed (21%). The median total number of symptoms was 6 (IQR 4-8). Self-selected dominant LC symptoms included fatigue (54%), breathlessness (16%), pain (12%), anxiety/depression (1%) and "other" (17%). At baseline, 82% were taking medication, 57% reported 1+ other medical conditions. Quality of life was poor; 20% were on long-term sick leave or reduced working hours. Most (92%) reported having gained weight since contracting COVID-19 (median weight change +11.5 kg, range -11.5 to +45.3 kg).
Conclusions: Symptoms linked to LC and overweight are diverse and complex. Remote trial delivery enabled rapid recruitment across the UK yet certain groups (e.g. men and those from ethnic minority groups) were under-represented.
Trial registration: ISRCTN registry ( ISRCTN12595520, 25/11/2021).
Care home residents are vulnerable to severe outcomes from infections such as COVID-19 and influenza. However, measures to control outbreaks, such as care home closures to visitors and new admissions, have a detrimental impact on their quality of life. Many infections and outbreaks could be prevented but the first step is to measure them reliably. This is challenging in care homes due to the lack of data and research infrastructure. During the pandemic, the VIVALDI study measured COVID-19 infections in residents and staff by partnering with care providers and using routinely collected data. This study aims to establish sentinel surveillance and a research database to enable observational and future interventional studies in care homes. The project has been co-produced with care providers, staff, residents, relatives, and researchers. The study (October 2023 to March 2025) will explore the feasibility of establishing a network of 500-1500 care homes for older adults in England that is underpinned by a linked data platform. No data will be collected from staff. The cohort will be created by regularly extracting resident identifiers from Digital Social Care Records (DSCR), followed by pseudonymisation and linkage to routinely collected datasets. Following extensive consultation, we decided not to seek informed consent from residents for data collection, but they can 'opt out' of the study. Our goal is to be inclusive, and it is challenging to give every resident the opportunity to 'opt in' due to cognitive impairment and the requirement for consultees. The project, and all requests to use the data will be overseen by relatives, residents, staff, and care providers. The study has been approved by the Health Research Authority Confidentiality Advisory Group (23/CAG/0134&0135) and the South-West Frenchay Research Ethics Committee (23/SW/0105). It is funded by the UK Health Security Agency.
Background: Gastrointestinal symptoms in cystic fibrosis (CF) are common and intrusive to daily life. Relieving gastrointestinal symptoms was identified as an important research priority and previously explored in an international survey in 2018. However, following the widespread introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators in 2019, the landscape of CF treatment has changed. We repeated an online survey to further describe gastrointestinal symptoms and their effect on quality of life (QoL) in the CFTR modulator era.
Methods: An electronic survey consisting of closed questions and free text responses was distributed via social media and professional networks for a period of one month between March - April 2022. People with CF (pwCF), their family and friends, and healthcare professionals (HCPs) were invited to take part.
Results: There were 164 respondents: 88 pwCF (54%), 22 (13%) family, and 54 (33%) healthcare professionals (HCPs). A total of 89/110 (81%) pwCF or family members reported CFTR modulator treatment. The most commonly reported symptoms were wind / gas and rumbling stomach noises (borborygmi) in both the modulator and non-modulator groups in addition to loose motions (modulator group) and bloating (no modulator group). Abdominal pain and bloating had the greatest impact on QoL.For those on a CFTR modulator, the proportion of pwCF reporting "no change" or "worse" for all of the symptoms surveyed was greater than the proportion reporting an improvement. For some symptoms such as stomach pains and reduced appetite, improvements were perceived more commonly in HCPs than what was reported by pwCF. Following modulator introduction, dietary changes to manage GI symptoms were recommended by 28/35 (80%) of HCPs and reported by 38/76 (50%) lay respondents. Changes in medication were recommended by 19/35 (54%) HCPs and reported by 44/76 (58%) of patients and family members.
Conclusion: This survey has shown that gastrointestinal symptoms remain prevalent in pwCF in the CFTR modulator era, though the nature of these symptoms may have changed. A better understanding of the underlying pathophysiology of these symptoms is essential. Future clinical studies should focus on improving symptoms and QoL.
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