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.

Quality of patient-reported outcome reporting in trials of diabetes in pregnancy: A systematic review.

AIMS: Patient-reported outcomes (PROs) are reports of the patient's health status that come directly from the patient without interpretation by the clinician or anyone else. They are increasingly used in randomised controlled trials (RCTs). In this systematic review we identified RCTs conducted in women with diabetes in pregnancy which included PROs in their primary or secondary outcomes. We then evaluated the quality of PRO reporting against an internationally accepted reporting framework (Consolidated Standards of Reporting Trials (CONSORT-PRO) guidelines). METHODS: We searched online databases for studies published 2013-2021 using a combination of keywords. Two authors reviewed all abstracts independently. Data on study characteristics and the quality of PRO reporting were extracted from relevant studies. We conducted a multiple regression analysis to identify factors associated with high quality reporting. RESULTS: We identified 7122 citations. Thirty-five articles were included for review. Only 17% of RCTs included a PRO as a primary or secondary outcome. Out of a maximum score of 100 the median score was 46, indicating sub-optimal reporting. A multiple regression analysis did not reveal any factors associated with high quality reporting. CONCLUSIONS: Researchers should be mindful of the importance of PRO inclusion and reporting and include reliable PROs in trials.

Approach to the Management of Hypernatraemia in Older Hospitalised Patients.

Hypernatraemia is associated with high morbidity and mortality and is more common in patients of older age, nursing home residents and those with cognitive impairment and restricted mobility. The most common cause in hospital settings is water dehydration due to reduced intake although other causes should be identified. Once identified, prompt management is necessary to avoid delayed correction as prolonged hypernatremia is associated with increased hospital stay and mortality. Comprehensive history-taking and physical examination, basic investigations and medication review are essential to identify causative and remediable factors in those admitted with hypernatraemia. Accurate calculation of fluid deficit and ongoing losses is essential in order to ensure adequate fluid replacement, The administration of appropriate, usually hypotonic, fluids is also essential to the timely restoration of eunatraemia. Although evidence of definite harm resulting from rapid correction is lacking, a serum sodium reduction rate of <12 mmol/l day is advised with the caveat that close monitoring of electrolytes is required to ensure the desired correction rate is being achieved. Medical and nursing professionals should have access to a local hospital protocol to guide management of patients with hypernatraemia to improve patient outcomes and mitigate the risk of harm, particularly from under-recognition and slow correction.

A Comparison of Community-Acquired and Hospital-Acquired Hypernatraemia in Patients who are Acutely Admitted to Hospital.

Background Hypernatraemia is associated with a short-term mortality of 20-60%. Age-related physiological changes predispose patients to hypernatraemia. This study reviewed acutely admitted patients comparing those with community-acquired (CAH) and hospital-acquired hypernatraemia (HAH). Methods A retrospective study of 102 consecutive acute medical in-patients with serum [Na]>145 mmol/L was conducted. Baseline characteristics, clinical presentation, laboratory values, monitoring, management and outcomes were compared between CAH and HAH groups. Results Patients were exclusively older (>69 years). Forty patients (39.2%) had CAH and sixty-two (61.8%) had HAH. Those with CAH were more likely to be NH residents, have dementia and reduced mobility. Most HAH patients had mild hypernatraemia initially (75.8%, n=47), and higher rates of acute kidney injury (27% (n=11) vs 8% (n=3)/p=0.02) were observed. Monitoring was inadequate and no patient had a free water deficit documented. Medication review and intravenous fluid prescribing was similar between groups. The median length of stay of discharged HAH patients was longer (22.5 vs 8 days/p=0.005). Mortality rates were similar (47% (n=29) vs 37% (n=15)/p=0.416). Time from admission to death was higher in HAH patients (16 vs 8 days/p=0.008). Conclusions Both CAH and HAH present similarly, however, older patients with cognitive/physical impairments are at an increased risk. Early identification of high-risk patients and adherence to best practice guidelines is required.

A systematic review on outcome reporting in randomised controlled trials assessing treatment interventions in pregnant women with pregestational diabetes.

BACKGROUND: Pregestational diabetes mellitus (PGDM) is associated with adverse pregnancy outcomes. Studies assessing interventions to improve maternal and infant outcomes have increased exponentially over recent years. Several outcomes in this field of maternal diabetes are rare, making it difficult to synthesise evidence. OBJECTIVES: To collect outcomes reported in studies assessing treatment interventions in pregnant women with PGDM. SEARCH STRATEGY: CENTRAL, Web of Science, Medline, CINAHL, Embase and ClinicalTrials.gov from their inception until 27 January 2020. SELECTION CRITERIA: Any randomised controlled trial assessing treatment interventions in pregnant women with PGDM reported in English. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed the suitability of articles and retrieved the data. Outcomes extracted from the literature were broadly categorised into maternal, fetal/infant or other outcomes by the study advisory group. MAIN RESULTS: Sixty-seven of the 1475 studies identified fulfilled the inclusion criteria. The median number of outcomes reported per study was 15 (range 1-46). The majority of studies were from North America and Europe. Insulin and metformin were the most commonly investigated pharmacological interventions. Glucose monitoring was the most assessed technological intervention. In all, 131 unique outcomes were extracted: maternal (n = 69), fetal/infant (n = 61) and other (n = 1). CONCLUSIONS: Outcome reporting in treatment interventions trials of pregnant women with PGDM is varied, making it difficult to synthesise evidence, especially for rare outcomes. Systems are needed to standardise outcome reporting in future clinical trials and so facilitate evidence synthesis in this area of maternal diabetes. REGISTRATION: The systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO) database (Registration number CRD42020173549). TWEETABLE ABSTRACT: Outcome reporting is heterogeneous in intervention trials of pregnant women with diabetes existing before pregnancy.

A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

Early gestational diabetes mellitus (GDM) is associated with worse pregnancy outcomes compared with GDM diagnosed at 24-28 weeks gestation despite early treatment.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated+ with adverse pregnancy outcomes compared with women with normal glucose tolerance in pregnancy. The WHO recommends screening at 24-28 weeks gestation for GDM. Women who are diagnosed before 24-28 weeks gestation have a longer intervention period which may impact positively on pregnancy outcomes. AIM: This study aimed to examine pregnancy outcomes of women with GDM diagnosed <24 weeks gestation compared with those diagnosed at 24-28 weeks in a large Irish cohort. METHODS: A retrospective cohort study of 1471 pregnancies in women with GDM diagnosed using IADPSG criteria between September 2012 and April 2016 was conducted. At GDM diagnosis, women were classified as early GDM <24 weeks or standard GDM 24-28 weeks gestation. RESULTS: Women with early GDM had a significantly greater risk of pregnancy-induced hypertension (12.4% vs. 5.3%; P < 0.05), post-partum haemorrhage (8.7% vs. 2.4%; P < 0.05) and post-partum glucose abnormalities (32% vs. 15.6%; P < 0.05). Their offspring had a greater risk of pre-maturity (10.9% vs. 6.6%; P < 0.05), stillbirth (1.4% vs. 0.5%; P < 0.05), large for gestational age (19.1% vs. 13.4% P < 0.05) and need neonatal intensive care (30.7% vs. 22.1%; P < 0.05) compared with offspring of women with standard GDM. Rates of C-section and pre-maturity were still higher in the early GDM group when the two groups where compared based on their post-natal OGTT. CONCLUSION: Early GDM women and their offspring are at greater risk of an adverse pregnancy outcome compared with those diagnosed at 24-28 weeks. In view of the abnormal post-natal glucose findings, early GDM may reflect a more advanced state in diabetes pathogenesis.

The leptin to adiponectin ratio (LAR) is reduced by sleeve gastrectomy in adults with severe obesity: a prospective cohort study.

Bariatric surgery is known to reduce leptin and increase adiponectin levels, but the influence of sleeve gastrectomy on the leptin: adiponectin ratio (LAR), a measure of insulin sensitivity and cardiovascular risk, has not previously been described. We sought to determine the influence of sleeve gastrectomy on LAR in adults with severe obesity.In a single centre prospective cohort study of adults undergoing laparoscopic sleeve gastrectomy over a four-month period in our unit, we measured LAR preoperatively and 12 months after surgery. Of 22 patients undergoing sleeve gastrectomy, 17 (12 females, 12 with type 2 diabetes) had follow-up LAR measured at 12.1 ± 1 months. Mean body weight decreased from 130.6 ± 30.8 kg to 97.6 ± 21.6 kg, body mass index (BMI) from 46.9 ± 7.8 to 35.3 ± 7.2 kg m-2 and excess body weight from 87.5 ± 31.3 to 41.3 ± 28.8% (all p < 0.001). The reduction in leptin from 40.7 ± 24.9 to 30.9 ± 30.5 ng/ml was not significant (p = 0.11), but adiponectin increased from 4.49 ± 1.6 to 8.93 ± 6.36 µg/ml (p = 0.005) and LAR decreased from 8.89 ± 4.8 to 5.26 ± 6.52 ng/µg (p = 0.001), equivalent to a 70.9% increase in insulin sensitivity. The correlation with the amount of weight lost was stronger for LAR than it was for leptin or adiponectin alone. In this single-centre, interventional prospective cohort, patients undergoing laparoscopic sleeve gastrectomy had a substantial reduction in their LAR after 12 months which was proportional to the amount of weight lost. This may indicate an improvement in insulin sensitivity and a reduction in cardiovascular risk.

Establishing Benefit from Vitamin D Supplementation - Adherence to Defined Criteria and Targeting of High-Risk Groups Essential?

BACKGROUND: Vitamin D is the one of the most common nutritional deficiencies worldwide, and insufficiency or deficiency can be associated with musculoskeletal and non-skeletal conditions such as cancer, cardiovascular disease and diabetes mellitus. OBJECTIVE: Recent data suggests that Vitamin D is relatively safe and toxicity is rarer than previously indicated. However, international guidelines regarding dosage and target plasma levels are conflicting. Moreover multiple well-designed studies of healthy older adults, unselected in terms of Vitamin D status, have revealed largely negative results (with the possible exception of older patients in care homes/hospitals) in terms of improvement in musculoskeletal and non-skeletal conditions to date. CONCLUSION: On that basis, it is suggested that future trials regarding Vitamin D supplementation should be carried out in high-risk groups. The use of published criteria for evaluating the effect of nutrients and targeting of individuals with Vitamin D insufficiency and deficiency for inclusion in such studies is also proposed. The identification of specific subgroups that will benefit from supplementation and replacement, and the establishment of a scientific basis for such therapy, should be possible with this approach.

Plasma glycated CD59 (gCD59), a novel biomarker for the diagnosis, management and follow up of women with Gestational Diabetes (GDM) - protocol for prospective cohort study.

BACKGROUND: The prevalence of Gestational Diabetes (GDM) is rising and with it the number of mothers and children at risk of adverse outcomes. As treatment has been shown to reduce adverse events, it is imperative that we identify all at-risk pregnant women. In Ireland, the national standard of care is selective screening with a 2-hour 75 g oral glucose tolerance test (OGTT). Aiming for universal screening is of utmost importance but this is difficult given the length, the unfeasibility and impracticability of the OGTT. We aim to assess if the novel biomarker glycated CD59 (gCD59) is a suitable contender for the OGTT in identifying women with GDM. METHODS: In this prospective cohort study, the study participants will be consecutive pregnant women at Galway University Hospital, Galway, Ireland. Samples for the plasma gCD59 biomarker will be taken together with routine bloods at the first antenatal visit, at weeks 24-28 at the time of routine 75 g OGTT, in trimester 3- and 12-weeks post-partum for women with GDM while having their routine post-partum 75 g OGTT. The constructed database will contain baseline information on each study participant, baseline laboratory data, follow-up laboratory data and pregnancy related outcomes. We aim to recruit a total of 2,000 participants over the project period and with a national GDM prevalence of 12-13%, we will have 240-260 subjects who meet OGTT criteria for GDM. Following regional prevalence, we expect to have 34-37 women who will develop either diabetes or pre-diabetes in the early post-partum period. The sensitivity and specificity of plasma gCD59 to predict the results of the OGTT will be assessed using nonparametric estimates of the receiver operating characteristic (ROC) curves and respective area under the ROC curve (AUROC). DISCUSSION: A body of clinical and experimental evidence supports a link between the complement system, complement regulatory proteins, and the pathogenesis of diabetes complications. Building on this research, our study plans to look at the plasma gCD59 capacity to classify pregnant women with normal or abnormal glucose tolerance but also to assess if plasma gCD59 can be used as an early predictor for GDM, for adverse pregnancy outcomes and/or post-partum glucose intolerance.

Increased rates of hypernatraemia during modest heatwaves in temperate climates.

BACKGROUND: Hypernatraemia is associated with morbidity and mortality, particularly in the older person. Last summer, Ireland experienced prolonged periods of excessive heat. The Irish meteorological service defines a heatwave as temperatures exceeding 25°C for five consecutive days. AIM: This study sought to compare the frequency of hypernatraemia (sodium (Na+) >145 mmol/l) observed during a modest heatwave with that during average ambient temperature in the temperate Irish climate. DESIGN: Retrospective cross-sectional analysis with nested case-control study. METHODS: The 10-day period from 24 June to 3 July in 2017 and 2018 were chosen as the control and heatwave periods, respectively. Patients aged >65 with at least one Na+ value recorded on the laboratory information system were included. Local meteorological data, age, gender and Na+ levels were evaluated. RESULTS: Maximum air temperatures were significantly higher during the heatwave period (mean 27°C vs. 16.8°C, P < 0.0001). Hypernatraemia was present in 3.6% (66/1840) of samples collected during the heatwave compared to 1.4% (23/1593) in the control period. The mean age of affected patients was similar in both groups, 75 years ±7 (P = 1.000). Almost half of participants (49.5%) were male. The frequency of hypernatraemia observed was not influenced by gender, P = 0.33. The median sodium concentrations were similar in both groups, P = 1.00. CONCLUSION: Hypernatraemia was 2.5 times more frequent in samples drawn during the heatwave compared to the control period. In this study, neither age nor gender impacted the profile of patients diagnosed with hypernatraemia. A modest rise in temperatures increases hypernatraemia rates in temperate climates.

Fulminant Skeletal Failure in a Centenarian: The Impact of Nutrition and Immobility.

This case describes a 103-year-old lady who presented from home with an incidental diagnosis of a left femoral fracture. She had no history of trauma and denied pain. She had a known diagnosis of osteoporosis, and sustained a fracture of the contralateral femur aged 93 which was managed conservatively. She was bed-bound with fixed contractures, poor oral intake and was non-compliant with prescribed calcium/vitamin D supplementation. Clinical biochemical measurements showed severe vitamin D deficiency and mild hypocalcaemia. Secondary hyperparathyroidism in the setting of an inappropriately normal phosphate suggested concurrent renal bone disease. Biomarkers of bone turnover were also consistent with bone remodelling. The history of prior fragility fractures, severe vitamin D deficiency and immobility supports a diagnosis of osteoporotic fracture, however other causes of spontaneous fracture were also considered. This case highlights the complexity of interpreting clinical biochemistry results in the setting of multi-morbidity and addresses the challenges of bone health management in the frail older person.

Spontaneous Insufficiency Fractures.

Spontaneous insufficiency fractures are caused by normal or physiological stress on weakened bone. The leading cause of insufficiency fractures is osteoporosis which has a propensity to affect older patients. Other causes or associated factors are disorders which affect bone metabolism, collagen formation, bone remodelling and medications such as bisphosphonates and glucocorticoids. Pathological fractures and abuse are important causes of unexplained fractures which warrant careful consideration. Spontaneous fractures of the long bones affect on average 1% of nursing home residents per year and tend to occur in patients who are bed-bound with joint contractures. Preventative measures for spontaneous insufficiency fractures include optimising nutrition to include an adequate intake of protein, calcium and vitamin D, maintaining mobility and preventing long periods of bed-rest and treatment of underlying pre-disposing conditions.

Associations between glycaemic control and activation of the renin-angiotensin-aldosterone system in participants with type 2 diabetes mellitus and hypertension.

Introduction Hyperglycaemia increases succinate concentrations and succinate receptor activation in the kidney resulting in renin release. The aim of our study was to determine if there is an association between glycaemic control as evidenced by glycated haemoglobin values and activation of the renin-angiotensin-aldosterone system in patients with type 2 diabetes mellitus and hypertension. Methods A cross-sectional study was conducted at Galway University Hospitals between December 2014 and March 2015. Participants ( n = 66) were identified following interrogation of the electronic database for patients with type 2 diabetes mellitus. Baseline clinical demographics, aldosterone, plasma renin activity, direct renin concentration, urea and electrolytes, glycated haemoglobin, cholesterol, urine sodium and albumin creatinine ratio were recorded. Results There was a significant positive linear correlation between glycated haemoglobin and renin (both plasma renin activity [ P = 0.002] and direct renin concentration [ P = 0.008]) and between serum creatinine and aldosterone measured using both radioimmunoassay ( P = 0.008) and immunochemiluminometric assay ( P = 0.008). A significant negative linear correlation was demonstrated between serum sodium and plasma renin activity ( P = 0.005) and direct renin concentration ( P = 0.015) and between estimated glomerular filtration rate and aldosterone measured using radioimmunoassay ( P = 0.02) and immunochemiluminometric assay ( P = 0.016). A significant negative linear correlation existed between urine sodium and plasma renin activity ( P = 0.04) and aldosterone measured using radioimmunoassay ( P = 0.045). Conclusions There is a direct positive association between glycaemic control and renin. We advocate for renin measurement to be part of the diabetologist's armamentarium to assess, guide and optimize therapeutic strategies in patients with diabetes.

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.

Screening for primary aldosteronism using the newly developed IDS-iSYS® automated assay system.

BACKGROUND: The recommended approach to screening for primary aldosteronism (PA) in at-risk populations is to determine the ratio of aldosterone concentration (serum (SAC)/plasma (PAC)) to renin measured in plasma as activity (PRA) or concentration (DRC). However, lack of assay standardisation mandates the need for method-specific decision thresholds and clinical validation in the local population. AIM: The study objective was to establish method-specific aldosterone: renin ratio (ARR) cut-offs for PA in men and women using the IDS-iSYS® assay system (IDS plc). METHODS: A prospective cohort study design was used. PAC and DRC were measured immunochemically in ethylenediamine-tetraacetic acid (EDTA) plasma on the IDS-iSYS® instrument. RESULTS: A total of 437 subjects (218 men, 219 women) were recruited including: healthy normotensive volunteers (n=266) and women taking the oral contraceptive pill (OCP; n=15); patients with essential hypertension (EH; n=128); confirmed PA (n=16); adrenal cortical carcinoma (ACC; n=3); Addison's disease (AD; n=4) and phaeochromocytoma/paraganglioma (PPGL; n=5). In this population, an ARR cut-off at >37.4 pmol/mIU provided 100% diagnostic sensitivity, 96% specificity and positive likelihood ratio for PA of 23:1. When the ARR decision threshold was stratified according to gender, a cut-off of >26.1 pmol/mIU in men and >113.6 pmol/mIU in women resulted in diagnostic sensitivity and specificity of 100%. CONCLUSION: This study demonstrates that decision thresholds for PA should not only be method-specific but also gender-specific. However, given the small number of PA patients (n=16), particularly women (n=4), further validation through a prospective study with a larger PA cohort is required before the thresholds presented here could be recommended for routine clinical use.