Drug therapies for reducing gastric acidity in people with cystic fibrosis.

BackgroundMalabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review.ObjectivesTo assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic and non-electronic database searches, handsearches of relevant journals,  abstract books and conference proceedings. Both authors double checked the reference lists of the searches Most recent search of the Group's Trials Register: 26 April 2021. On the 26 April 2021 further searches were conducted on the clinicaltrials.gov register to identify any ongoing trials that may be of relevance. The WHO ICTRP database was last searched in 2020 and is not currently available for searching due to the Covid-19 pandemic.Selection criteriaAll randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment.Data collection and analysisBoth authors independently selected trials, assessed trial quality and extracted data.Main resultsThe searches identified 40 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival.Authors' conclusionsTrials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions

Extreme Premature Small for Gestational Age Infants Have Appropriate Catch-up Growth at Term Equivalence Compared with Extreme Premature Appropriate for Gestational Age Infants

Recent studies have shown that small for gestational age (SGA) term infants undergo catch-up growth during infancy but there is limited studies on early growth outcomes of extreme premature SGA infants. The aim of this study was to compare factors associated during birth in extremely premature infants less than 28 weeks’ gestation who were born SGA (<10th percentile for gestational age) with those who were born appropriate-for-gestational age (AGA) (10th-89th percentile) and to determine whether there was catch-up growth at term equivalence. One hundred fifty-three extreme premature infants (89 males) born below 28 weeks’ gestation were prospectively recruited. All infants had auxological measurements undertaken and prospective data on pregnancy, maternal factors, perinatal and postnatal data obtained. SGA infants at birth had significantly higher Clinical Risk Index for Babies scores and mortality, lower birth weight, smaller head circumference, smaller mid arm circumference and shorter leg length at time of birth compared with AGA infants. However, at term equivalence, weight and leg length of were not significant between AGA and SGA infants born at extreme prematurity. Our study shows that extreme premature SGA infants have appropriate catch-up growth by the time they reach term equivalence suggesting that postnatal nutrition and care are important determinants of catch-up growth in SGA infants

Neurodevelopmental Outcomes at 42 Months After Thyroxine Supplementation in Infants Below 28 Weeks' Gestation: A Randomized Controlled Trial.

Background: Infants below 28 weeks' gestation have low thyroid hormone plasma levels compared with more mature infants and this may contribute to their risk of developmental disability. We aimed at determining the effect of supplementation with levothyroxine (LT4) for extremely premature infants born below 28 weeks' gestations on neurodevelopmental outcomes at 42 months. Methods: An explanatory double-blind, randomized, placebo-controlled trial consecutively recruited 153 infants below 28 weeks' gestation from 5 neonatal units in the United Kingdom. Infants were either supplemented with LT4 started intravenously during the first 5 days after birth and then changed to oral LT4 when enteral feeds were fully established (8 μg/kg birthweight/day as a single daily dose) or given placebo until 32 weeks' corrected gestational age. Neurodevelopmental outcomes at 42 months (range 40-43) were evaluated in 59 of these infants (30 LT4-supplemented, 29 placebo) by using Bayley III Mental and Psychomotor Developmental Indices. Cognition outcomes was correlated with plasma free thyroxine (fT4) level at 36 weeks and diffusion tensor imaging (DTI) markers. Results: The LT4 supplemented group performed significantly better in motor, language, and cognitive function domains. The mean of the difference between each group (95% confidence intervals [CI], p-value) was motor domain 6.96 ([0.55-13.38], p = 0.034); language domain 8.93 ([0.16-17.70], p = 0.041); and cognition domain 6.35 ([0.14-12.55], p = 0.045). Neurodevelopmental outcome at 42 months had some associations with the trial's primary outcome (subarachnoid space width and motor outcome, p = 0.03), plasma fT4 level at 36 weeks (fT4 and cognition outcome, p = 0.01), and DTI at 36 weeks with cognition outcomes (p > 0.05). Conclusion: Our data suggest that early supplementation with LT4 may improve long-term neurodevelopment in infants born below 28 weeks' gestation, but larger trials are warranted as the current reported improvements shown are not strong enough to warrant a change in practice

Bridging the Digital Divide: The UNBIASED national study to unravel the impact of ethnicity and deprivation on diabetes technology disparities in the United Kingdom

While diabetes technology offers significant clinical and quality-of-life benefits to people with type 1 diabetes, persistent inequalities in technology use based on ethnicity and deprivation are becoming increasingly evident. To date, there is limited research into the challenges and barriers to accessing and using diabetes technology and concerns felt by end-users from racially minoritised and socioeconomically disadvantaged groups. Their views are often under-represented in the literature, and healthcare professionals’ perspectives on barriers to technology access have also been neglected. This article explores the nuanced relationship between ethnicity, socioeconomic status, and technology access. By understanding the parallels between health and technology inequalities, we can pave the way for targeted interventions to bridge the digital gap and create a more inclusive technological landscape. The UNBIASED study is currently being conducted across England, and is exploring the lived experiences of under-represented children and young people with type 1 diabetes regarding the (lack of) utilisation of life-changing diabetes technologies. The study is also consulting healthcare professionals who can act as gatekeepers to technology, with the ultimate goal of identifying and dismantling existing barriers and inequities to access. By synthesising the perspectives of both people with type 1 diabetes and healthcare providers, this research seeks to develop inclusive, practical, and implementable solutions to foster improved access to cutting-edge diabetes technologies within the National Health Service (NHS)

The impact of networks on clinical trials in the United Kingdom

The conduct of clinical trials in the UK has been affected by the recent introduction of managed clinical networks, clinical research networks and rigorous governance regulations. This commentary considers the challenges that these changes have posed for clinical triallists in the UK, based on experiences derived in the conduct of a multicentre neonatal clinical trial under the conditions that now prevail. We conclude that the considerable skills and knowledge that are now required to be an effective Principal Investigator should be recognised and that application processes, including issuing honorary contracts, should be simplified and centralised

Internet analytics of an innovative digital educational resource of type 1 diabetes HelloType1 in local languages for people living with diabetes families and healthcare professionals in Southeast Asia.

BackgroundThere is minimal data of health outcomes for Type 1 Diabetes (T1D) in Southeast Asia (SEA) where government funding of insulin and blood glucose monitoring either do not exist or is limited. The full impact of Covid-19 pandemic on the national economies of SEA remain unknown. In the midst of the pandemic, in 2021, HelloType1 was developed by Action4Diabetes (A4D), a non-government organisation charity in collaboration with Southeast Asia local healthcare professionals as an innovative digital educational resource platform of T1D in local languages. HelloType1 was launched in Cambodia, Vietnam, Thailand and Malaysia in 2021 to 2022 with Memorandums of Understandings (MOUs) signed between A4D and each country. Internet data analytics were undertaken between the 1st of January 2022 to 31st of December 2022.AimsThe aims of this study were to explore the usability and internet data analytics of the HelloType1 online educational platform within each country.MethodsThe data analytics were extracted Google analytics that tracks data from the website hellotype1.com and Facebook analytics associated with the website.ResultsThere was a 147% increase in the number of HelloType1 users between the first 6 months versus the latter 6 months in 2022 and a 15% increase in the number of pages visited were noted. The majority of traffic source were coming from organic searches with a significant increase of 80% growth in 2022.ConclusionsThe results of the analytics provide important insights on how an innovative diabetes digital educational resource in local languages may be optimally delivered in low-middle income countries with limited resources

Induction of cell cycle arrest and apoptosis by copper complex Cu(SBCM)₂ towards oestrogen-receptor positive MCF-7 breast cancer cells

Copper complexes have the potential to be developed as targeted therapy for cancer because cancer cells take up larger amounts of copper than normal cells. Copper complex Cu(SBCM)2 has been reported to induce cell cycle arrest and apoptosis towards triple-negative breast cancer cells. Nevertheless, its effect towards other breast cancer subtypes has not been explored. Therefore, the present study was conducted to investigate the effect of Cu(SBCM)₂ towards oestrogen-receptor positive MCF-7 breast cancer cells. Growth inhibition of Cu(SBCM)₂ towards MCF-7 and human non-cancerous MCF-10A breast cells was determined by MTT assay. Morphological changes of Cu(SBCM)2-treated-MCF-7 cells were observed under an inverted microscope. Annexin V/PI apoptosis assay and cell cycle analysis were evaluated by flow cytometry. The expression of wild-type p53 protein was evaluated by Western blot analysis. The intracellular ROS levels of MCF-7 treated with Cu(SBCM)₂ were detected using DCFH-DA under a fluorescence microscope. The cells were then co-treated with Cu(SBCM)₂ and antioxidants to evaluate the involvement of ROS in the cytotoxicity of Cu(SBCM)2. Docking studies of Cu(SBCM)2 with DNA, DNA topoisomerase I, and human ribonucleotide reductase were also performed. The growth of MCF-7 cells was inhibited by Cu(SBCM)2 in a dose-dependent manner with less toxicity towards MCF-10A cells. It was found that Cu(SBCM)₂ induced G2/M cell cycle arrest and apoptosis in MCF-7 cells, possibly via a p53 pathway. Induction of intracellular ROS was not detected in MCF-7 cells. Interestingly, antioxidants enhance the cytotoxicity of Cu(SBCM)2 towards MCF-7 cells. DNA topoisomerase I may be the most likely target that accounts for the cytotoxicity of Cu(SBCM)₂

A qualitative study on relationships and perceptions between managers and clinicians and its effect on value-based healthcare within the national health service in the UK.

One of the main drivers for change towards delivering value-based healthcare is to improve clinical and managerial culture and engagement within organisations. The relationships between clinicians and managers in an organisation are often considered to be either an enabler or disabler towards successful engagement to develop strategies towards better value healthcare. Successful engagement is dependent on effective and transformational leadership that can impact on organisational value in healthcare. The aim of this research was to explore the relationships, behaviours and perceptions between managers and clinicians towards value-based healthcare in the National Health Service in the United Kingdom. A qualitative research methodology of semi-structured in-depth interviewing on a sample consisting of hospital consultants, senior managers and board executives from a diverse group were conducted. A thematic analysis was used to analyse the data using a systematic approach. The study findings identified areas of potential barriers to engagement for clinicians and managers which were related to regulatory burden, financial challenges and workforce shortages. Key recommendations on what will be required to improve clinicians and managers engagement and the leadership approaches towards improving value-based healthcare are discussed