Electronic reporting of rare endocrine conditions within a clinical network: results from the EuRRECa project.

Objective: The European Registries for Rare Endocrine Conditions (EuRRECa, eurreb.eu) includes an e-reporting registry (e-REC) used to perform surveillance of conditions within the European Reference Network (ERN) for rare endocrine conditions (Endo-ERN). The aim of this study was to report the experience of e-REC over the 3.5 years since its launch in 2018. Methods: Electronic reporting capturing new encounters of Endo-ERN conditions was performed monthly through a bespoke platform by clinicians registered to participate in e-REC from July 2018 to December 2021. Results: The number of centres reporting on e-REC increased to a total of 61 centres from 22 countries. A median of 29 (range 11, 45) paediatric and 32 (14, 51) adult centres had reported cases monthly. A total of 9715 and 4243 new cases were reported in adults (age ≥18 years) and children, respectively. In children, sex development conditions comprised 40% of all reported conditions and transgender cases were most frequently reported, comprising 58% of sex development conditions. The median number of sex development cases reported per centre per month was 0.6 (0, 38). Amongst adults, pituitary conditions comprised 44% of reported conditions and pituitary adenomas (69% of cases) were most commonly reported. The median number of pituitary cases reported per centre per month was 4 (0.4, 33). Conclusions: e-REC has gained increasing acceptability over the last 3.5 years for capturing brief information on new encounters of rare conditions and shows wide variations in the rate of presentation of these conditions to centres within a reference network. Significance statement Endocrinology includes a very wide range of rare conditions and their occurrence is often difficult to measure. By using an electronic platform that allowed monthly reporting of new clinical encounters of several rare endocrine conditions within a defined network that consisted of several reference centres in Europe, the EuRRECa project shows that a programme of e-surveillance is feasible and acceptable. The data that have been collected by the e-reporting of rare endocrine conditions (e-REC) can allow the continuous monitoring of rare conditions and may be used for clinical benchmarking, designing new studies or recruiting to clinical trials.

A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol.

BACKGROUND: Pregnancies affected by gestational diabetes mellitus (GDM) are associated with an increased risk of adverse maternal and foetal outcomes. Current treatments for GDM involve initial medical nutritional therapy (MNT) and exercise and pharmacotherapy in those with persistent hyperglycaemia. Insulin is considered first-line pharmacotherapy but is associated with hypoglycaemia, excessive gestational weight gain (GWG) and an increased caesarean delivery rate. Metformin is safe in selected groups of women with GDM but is not first-line therapy in many guidelines due to a lack of long-term data on efficacy. The EMERGE trial will evaluate the effectiveness of early initiation of metformin in GDM. METHODS: EMERGE is a phase III, superiority, parallel, 1:1 randomised, double-blind, placebo-controlled trial comparing the effectiveness of metformin versus placebo initiated by 28 weeks (+6 days) plus usual care. Women aged 18-50 years will be recruited. Women with established diabetes, multiple pregnancies, known major congenital malformation or small for gestational age (<10th centile), intolerance or contraindication to the use of metformin, shock or sepsis, current gestational hypertension or pre-eclampsia, significant gastrointestinal problems, congestive heart failure, severe mental illness or galactose intolerance are excluded. INTERVENTION: Immediate introduction of metformin or placebo in addition to MNT and usual care. Metformin is initiated at 500mg/day and titrated to a maximum dose of 2500mg over 10 days. Women are followed up at 4 and 12 weeks post-partum to assess maternal and neonatal outcomes. The composite primary outcome measure is initiation of insulin or fasting blood glucose ≥ 5.1 mmol/L at gestational weeks 32 or 38. The secondary outcomes are the time to insulin initiation and insulin dose required; maternal morbidity at delivery; mode and time of delivery; postpartum glucose status; insulin resistance; postpartum body mass index (BMI); gestational weight gain; infant birth weight; neonatal height and head circumference at delivery; neonatal morbidities (neonatal care unit admission, respiratory distress, jaundice, congenital anomalies, Apgar score); neonatal hypoglycaemia; cost-effectiveness; treatment acceptability and quality of life determined by the EQ5D-5L scale. DISCUSSION: The EMERGE trial will determine the effectiveness and safety of early and routine use of metformin in GDM. TRIAL REGISTRATION: EudraCT Number 2016-001644-19l; NCT NCT02980276 . Registered on 6 June 2017.

Outcomes of Patients with a pH<7.0 Presenting to the Emergency Department (OPpHED Study).

Objectives The aim of this study was to assess the mortality and predictive factors in patients presenting with a pH<7.0 to the emergency department (ED). Methods A retrospective study of patients presenting to the ED of University Hospital Galway with a pH<7.0 from January 2014 to December 2017 was performed. A pH<7.0 on arrival to the ED from either an arterial or venous sample as measured by the blood gas analyser machine were assessed for inclusion. Results A total of 130 patients presented to ED over a 4-year period, with a mean age of 58 ±20 years. Eighty-one (63%) patients of the total cohort were male. In terms of aetiology of presentation, 66 (51%) cases were from cardiac arrest (CA), while the remaining 64 (49%) cases were non-cardiac arrest (NCA) related. Twenty-eight-day mortality was 69.5% overall, with significant mortality in the CA group (89%) compared to the NCA group (48%) (p<0.00). A modified early warning score (MEWS) (odds ratio [OR] 1.37, 95% CI: 1.18-1.59) and PCO2 ([OR] 1.35, 95% CI: 1.08-1.68.) were predictive of mortality. Conclusion In patients presenting to the ED with a pH of <7.0 the overall mortality was 69.5%, with survival more likely in NCA aetiologies. Mortality was associated with higher pCO2 and MEWS.

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline.

An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted, and the evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. If the evidence was insufficient or lacking, then the conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on the induction of puberty with follicle-stimulation hormone and human chorionic gonadotrophin in hypogonadotropic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommends that pubertal induction or sex hormone replacement to sustain puberty should be cared for by a multidisciplinary team. Children with a known condition should be followed from the age of 8 years for girls and 9 years for boys. Puberty induction should be individualised but considered at 11 years in girls and 12 years in boys. Psychological aspects of puberty and fertility issues are especially important to address in individuals with sex development disorders or congenital pituitary deficiencies. The transition of these young adults highlights the importance of a multidisciplinary approach, to discuss both medical issues and social and psychological issues that arise in the context of these chronic conditions.

Running a safe and effective Cleft Network Service in response to the COVID-19 pandemic.

Maintaining an excellent level of service in a network Cleft Lip and Palate service in the UK has been an added challenge for both clinicians and patients throughout the COVID-19 pandemic. We describe the changes to our service, and report a high level of patient satisfaction with the changes. Some of the enforced changes may last beyond the duration of this pandemic.

Diabetes care and pregnancy outcomes for women with pregestational diabetes in Ireland.

AIMS: Pre-gestational diabetes mellitus (PGDM) is associated with adverse outcomes. We aimed to examine pregnancies affected by PGDM; report on these pregnancy outcomes and compare outcomes for patients with type 1 versus type 2 diabetes mellitus; compare our findings to published Irish and United Kingdom (UK) data and identify potential areas for improvement. METHODS: Between 2016 and 2018 information on 679 pregnancies from 415 women with type 1 Diabetes Mellitus and 244 women with type 2 diabetes was analysed. Data was collected on maternal characteristics; pregnancy preparation; glycaemic control; pregnancy related complications; foetal and maternal outcomes; unscheduled hospitalisations; congenital anomalies and perinatal deaths. RESULTS: Only 15.9% of women were adequately prepared for pregnancy. Significant deficits were identified in availability and attendance at pre-pregnancy clinic, use of folic acid, attaining appropriate glycaemic targets and appropriate retinal screening. The majority of pregnancies (n = 567, 83.5%) resulted in a live birth but the large number of infants born large for gestational age (LGA) (n = 280, 49.4%), born prematurely <37 weeks and requiring neonatal intensive care unit (NICU) admission continue to be significant issues. CONCLUSIONS: This retrospective cohort study identifies multiple targets for improvements in the provision of care to women with pre-gestational DM which are likely to translate into better pregnancy outcomes.

Evidence of Small Airways Disease and the Immediate Effects of Lumacaftor/Ivacaftor in Children with Cystic Fibrosis.

Aim The aim of this study was to explore risk factors for acute changes in lung function following initiation of lumacaftor/ivacaftor (LUM/IVA) in children with cystic fibrosis. Methods Retrospective review of all children commenced on LUM/IVA treatment over a one-year period. CT Thorax images were reviewed for evidence of air trapping using the Brody score. Results Data was collected from 15 children. A transient decline in ppFEV1 was observed after initiation of LUM/IVA in 93% (n=14) of patients with an absolute mean decline of -10.8%. There was a statistically significant inverse relationship between ΔFEV1 and baseline ppFEV1. There was no relationship between air trapping score and ΔFEV1 (p=0.41). Conclusion Pre-existing small airways disease is not a risk factor for acute changes in lung function following initiation of LUM/IVA. Our results suggest that a LUM/IVA-related decline in lung function is more significant in CF children with higher baseline FEV1.

Do current clinical trials in cystic fibrosis match the priorities of patients and clinicans? A systematic review.

There are many uncertainties regarding Cystic Fibrosis (CF) treatment. Recently, the first James Lind Alliance (JLA) Priority Setting Partnership (PSP) in CF was completed, bringing clinicians, patients and carers together to identify the Top 10 research priorities. Here we investigate how well the current clinical trials landscape reflects these priorities. Trials in CF were identified through searches of research databases (Pubmed, ANZCTR, EU clinical trials register, ClinicalTrials.gov and ISRCTN). Trials meeting inclusion criteria of registered intervention studies in CF published between 01.012016 and 11.09.2017 were matched to the Top 10 priorities. We identified 259 trials, with 193 fulfilling the inclusion criteria. Only 63 (33%) of these matched one or more of the JLA priorities showing that current clinical trials poorly reflect the JLA Top 10. By increasing awareness of the Top 10 priorities, it is hoped that this will fuel future research in areas important to the CF community.

An Irish National Diabetes in Pregnancy Audit: aiming for best outcomes for women with diabetes.

AIMS: The purpose of this study was to identify the number of pregnancies affected by pre-gestational diabetes in the Republic of Ireland; to report on pregnancy outcomes and to identify areas for improvement in care delivery and clinical outcomes. METHODS: Healthcare professionals caring for women with pre-gestational diabetes during pregnancy were invited to participate in this retrospective study. Data pertaining to 185 pregnancies in women attending 15 antenatal centres nationally were collected and analysed. Included pregnancies had an estimated date of delivery between 1 January and 31 December 2015. RESULTS: The cohort consisted of 122 (65.9%) women with Type 1 diabetes and 56 (30.3%) women with Type 2 diabetes. The remaining 7 (3.8%) pregnancies were to women with maturity-onset diabetes of the young (MODY) (n = 6) and post-transplant diabetes (n = 1). Overall women were poorly prepared for pregnancy and lapses in specific areas of service delivery including pre-pregnancy care and retinal screening were identified. The majority of pregnancies 156 (84.3%) resulted in a live birth. A total of 103 (65.5%) women had a caesarean delivery and 58 (36.9%) infants were large for gestational age. CONCLUSIONS: This audit identifies clear areas for improvement in delivery of care for women with diabetes in the Republic of Ireland before and during pregnancy.

Can exercise replace airway clearance techniques in cystic fibrosis? A survey of patients and healthcare professionals.

Airway clearance techniques (ACTs) are recommended in cystic fibrosis (CF) to prevent accumulation of secretions and lung infection. "Can exercise replace chest physiotherapy for people with CF?" is one of the CF community's top 10 research questions. We conducted an online survey of the CF community to gather data on current ACT use, recommendations, reported adherence levels and exercise strategies used. There were 488 respondents: 194 (40%) people with CF (pwCF), 141 (29%) family and 153 (31%) healthcare professionals (HCPs) (mostly physiotherapists). Only 10/285 (4%) of pwCF do no exercise at present and 163/303 (54%) already incorporate exercise into ACTs. ACTs were omitted by 128/267 (48%) of pwCF when they exercised. Nearly all (110/129, 93%) of HCPs currently recommend exercise to support ACTs. A trial replacing some or all ACTs with exercise, was supported by 80/110 (73%) of HCPs, with an additional 9/110 (8%) willing to consider in selected patients.

Adapting the James Lind Alliance priority setting process to better support patient participation: an example from cystic fibrosis.

PLAIN ENGLISH SUMMARY: Cystic fibrosis (CF) is the commonest life-limiting inherited disorder in the UK. It affects many parts of the body including the lungs and gut leading to increased infection and problems digesting food. People with CF need to undergo many treatments each day throughout their whole lives. These include tablets, inhalers and breathing exercises, which are a huge burden, taking up several hours every dayIt is therefore, really important that the treatments we give are supported by good evidence, usually gathered from clinical trials. Unfortunately, we do not have good evidence for many of the CF treatments. We recently ran an exercise known as a James Lind Alliance Priority Setting Partnership (JLA PSP) to find out which the CF community feel are the top priority research questions. People with CF and those who look after them suggested questions to be answered by clinical trials. Through a series of online surveys and workshops these were then shortlisted to give a final top ten.Due to infection risk people with CF are advised not to mix, this meant we had to do things differently to the usual way JLA PSPs are carried out. We used videoconferencing to enable multiple people with CF to participate. Surveys were accessible online and promoted through social media. ABSTRACT: Background The James Lind Alliance (JLA) method is well recognised for setting research priorities. The JLA approach involves a combination of surveys and workshop interactions between patients, carers and health care professionals to identify and agree on a "top ten" list of research questions. Respiratory infection is one of the hallmarks of cystic fibrosis (CF). To avoid cross infection, patients are advised not to meet face to face, preventing us following standard JLA methodology. Here we describe adaptations made during our recent JLA Priority Setting Partnership (PSP) in CF. Methods We elicited and prioritised research questions, using sequential online surveys, promoted through social media. People with CF participated in steering committee meetings and the final workshop, using videoconferencing. Alterations to workshop methodology enabled participants attending in person and those joining remotely, to contribute equally. We also altered the JLA methodology to include "lone" questions, asked by only one survey respondent. We are now working with the CF community to co-produce research projects that answer these top ten. Results There were 482 respondents, from 23 countries, who submitted 1080 questions. Increases in the number of responses occurred just after promotion on social media. Use of videoconferencing enabled participation of multiple people with CF and ensured participation from anywhere in the world, including hospital inpatients. Inclusion of lone questions resulted in one being included in our top ten. Conclusions There is no "one-size-fits-all" for patient involvement methodologies. Through altering the JLA methods to fit our patient group we achieved wide participation. We believe that methods used in our project may also be applied to future partnerships to increase participation, especially where people may be hospitalised or be unable to travel. The methodology we are developing through the JLA PSP CF2 project may be useful for other PSPs to follow.

Velopharyngeal insufficiency after maxillary advancement in patients with cleft palate - a survey of risk assessment in the United Kingdom and Ireland.

Patients with cleft lip and palate may require orthognathic surgery to correct severe impairments in midfacial growth. Maxillary advancement in this group, however, is linked to deterioration in velopharyngeal function (VPF), and it is not clear how cleft teams assess this risk. We therefore surveyed surgeons from 15 cleft units who provide orthognathic treatment, to gain an understanding of current practice in the UK and Ireland. A total of 16/21 surgeons from 14/15 units responded. While 14/16 surgeons agreed that these patients are at risk of a deterioration in VPF after maxillary advancement, two disagreed. Preoperative assessment of perceptual speech is required in all cases, but only 9/14 routinely did an instrumental assessment of VPF. One third of respondents thought that they could not identify "borderline" cases. There were differences in how surgeons obtained preoperative consent regarding deterioration in VPF, and whether surgical plans should be modified accordingly. There was considerable variation in current practice regarding risk, assessment, and management of potential changes in VPF after orthognathic surgery. A national forum for multidisciplinary discussion would allow for the standardisation of care across the UK and Ireland. Further study is needed to establish the effects of orthognathic surgery on VPF in this group, as well as the clinical benefits of instrumental assessments.

The current landscape of European registries for rare endocrine conditions.

Objective To identify cross-border international registries for rare endocrine conditions that are led from Europe and to understand the extent of engagement with these registries within a network of reference centres (RCs) for rare endocrine conditions. Methods Database search of international registries and a survey of RCs in the European Reference Network for rare endocrine conditions (Endo-ERN) with an overall response rate of 82%. Results Of the 42 conditions with orphacodes currently covered within Endo-ERN, international registries exist for 32 (76%). Of 27 registries identified in the Orphanet and RD-Connect databases, Endo-ERN RCs were aware of 11 (41%). Of 21 registries identified by the RC, RD-Connect and Orphanet did not have a record of 10 (48%). Of the 29 glucose RCs, the awareness and participation rate in an international registry was highest for rare diabetes at 75 and 56% respectively. Of the 37 sex development RCs, the corresponding rates were highest for disorders of sex development at 70 and 52%. Of the 33 adrenal RCs, the rates were highest for adrenocortical tumours at 68 and 43%. Of the 43 pituitary RCs, the rates were highest for pituitary adenomas at 43 and 29%. Of the 31 genetic tumour RCs, the rates were highest for MEN1 at 26 and 9%. For the remaining conditions, awareness and participation in registries was less than 25%. Conclusion Although there is a need to develop new registries for rare endocrine conditions, there is a more immediate need to improve the awareness and participation in existing registries.

Out-of-hospital cardiac arrest termination of resuscitation with ongoing CPR: An observational study.

INTRODUCTION: Termination of resuscitation guidelines for out-of-hospital cardiac arrest can identify patients in whom continuing resuscitation has little chance of success. This study examined the outcomes of patients transferred to hospital with ongoing CPR. It assessed outcomes for those who would have met the universal prehospital termination of resuscitation criteria (no shocks administered, unwitnessed by emergency medical services, no return of spontaneous circulation). METHODS: A retrospective cohort study of consecutive adult patients who were transported to hospital with ongoing CPR was conducted at three hospitals in the West Midlands, UK between September 2016 and November 2017. Patient characteristics, interventions and response to treatment (ROSC, survival to discharge) were identified. RESULTS: 227 (median age 69 years, 67.8% male) patients were identified. 89 (39.2%) met the universal prehospital termination of resuscitation criteria. Seven (3.1%) were identified with a potentially reversible cause of cardiac arrest. After hospital arrival, patients received few specialist interventions that were not available in the prehospital setting. Most (n = 210, 92.5%) died in the emergency department. 17 were admitted (14 to intensive care), of which 3 (1.3%) survived to hospital discharge. There were no survivors (0%) in those who met the criteria for universal prehospital termination of resuscitation. CONCLUSION: Overall survival amongst patients transported to hospital with ongoing CPR was very poor. Application of the universal prehospital termination of resuscitation rule, in patients without obvious reversible causes of cardiac arrest, would have allowed resuscitation to have been discontinued at the scene for 39.2% of patients who did not survive.

Vitamin D Deficiency and Insufficiency Prevalence in the West of Ireland - A Retrospective Study.

OBJECTIVES: Vitamin D plays an important role in calcium homeostasis and is essential for normal bone growth and remodeling. Previous studies of acutely ill and institutionalized older women in Galway revealed that vitamin D insufficiency is extremely common. We aimed to evaluate age and gender-related rates of vitamin D insufficiency and deficiency in adult patients attending their General Practitioners in the same region. DESIGN: A retrospective cohort study. SETTING: General practices in Galway, a city located on the west coast of Ireland, latitude 53.17 North. PARTICIPANTS: A total of 15,708 consecutive blood samples from adults attending their General Practitioners between January 2013 and December 2014 were sent to the Clinical Biochemistry Laboratory in the University Hospital Galway for vitamin D level testing. 73% were from women. INTERVENTION: Data were collected and grouped according to age, sex and season. Vitamin D levels (25OHD) were categorised into deficiency (<25nmol/L), insufficiency (25-50nmol/L) and sufficiency ( >50nmol/L). MEASUREMENTS: Median and interquartile range were reported as vitamin D levels were not normally distributed. Descriptive statistics were performed using STATA/MP 13.1 for Mac. RESULTS: While vitamin D levels were sufficient in 56.4% (n=8,496), they were insufficient in 32.4% (n=4,891) and deficient in 11.2% (n=1,691). Of the deficient group, 19%( 325) had levels <15nmol/L consistent with profound deficiency. Men were more likely than women to be deficient (12% (n=489) vs. 10.9% (n=1,202)) and insufficient (38.0% (n=1,550) vs. 30.4% (n=3,341)) (p<0.01). Highest rates of deficiency were seen in those 81-97 years (19.4% (n=136)) and 18-40 years (13.8% (n=543)), the former group showing less seasonal variation. CONCLUSION: Overall prevalence of insufficiency is similar to those in national and European studies published recently. However, there is a high possibility that those most vulnerable to vitamin D deficiency were underrepresented in this cohort, when results from previous studies in the same region are considered. Further prospective studies are needed to guide treatment with supplementation of vitamin D for appropriate subgroups.

Ear health and hearing surveillance in girls and women with Turner's syndrome: recommendations from the Turner's Syndrome Support Society.

BACKGROUND: Turner's syndrome (TS) is a common chromosomal disorder, affecting one in 2000 newborn girls, in which part or all of one X chromosome is missing. Ear and hearing problems are very common in girls and women with TS. The aim of this review was to review the published literature to suggest recommendations for otological health surveillance. METHOD: A keyword search of Ovid Medline was performed for published literature on the subject and evidence rated according to the GRADE criteria. RESULTS: Middle ear disorders are very common and persistent in girls and women with TS as are progressive sensorineural hearing loss and balance disorders. CONCLUSIONS: Otolaryngologists should be aware of the high prevalence and challenging nature of all forms of ear disease in individuals with TS. Early intervention may offer benefits to health and education, and we advocate routine lifelong annual hearing screening in this group.