HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank.

OBJECTIVES: HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort. DESIGN: Prospective cohort study. SETTING: 22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010). PARTICIPANTS: 451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data. MAIN OUTCOME MEASURES: Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years. RESULTS: 12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes. CONCLUSIONS: Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.

Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent ß-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial.

INTRODUCTION: Despite the improvement in medical management, many patients with transfusion-dependent ß-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent ß-thalassaemia with very high iron overload. METHODS AND ANALYSIS: This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent ß-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures. ETHICS AND DISSEMINATION: Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals. TRIAL REGISTRATION NUMBER: The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).

Effects of ferric derisomaltose on postoperative anaemia in adult spinal deformity surgery: a study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative anaemia is prevalent in adult spinal deformity (ASD) surgery in association with unfavourable outcomes. Ferric derisomaltose, a novel iron supplement, offers a promising solution in rapidly treating postoperative anaemia. However, the clinical evidence of its effect on patients receiving spinal surgery remains inadequate. This randomised controlled trial aims to evaluate the safety and efficacy of ferric derisomaltose on postoperative anaemia in ASD patients. METHODS AND ANALYSIS: This single-centre, phase 4, randomised controlled trial will be conducted at Department of Orthopaedics at Peking Union Medical College Hospital and aims to recruit adult patients who received ASD surgery with postoperative anaemia. Eligible participants will be randomly assigned to receive ferric derisomaltose infusion or oral ferrous succinate. The primary outcome is the change in haemoglobin concentrations from postoperative days 1-14. Secondary outcomes include changes in iron parameters, reticulocyte parameters, postoperative complications, allogeneic red blood cell infusion rates, length of hospital stay, functional assessment and quality-of-life evaluation. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of Peking Union Medical College Hospital and registered at ClinicalTrials.gov. Informed consent will be obtained from all participants prior to enrolment and the study will be conducted in accordance with the principles of the Declaration of Helsinki. The results of this study are expected to be disseminated through peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT05714007.

Hypertriglyceridaemic waist phenotype and waist circumference triglyceride index are associated with higher incidence of acute pancreatitis: a nationwide population-based retrospective cohort study.

OBJECTIVES: The hypertriglyceridaemic waist (HTGW) phenotype, an indicator to assess metabolic syndrome, could be a useful predictive marker for the risk of acute pancreatitis. This study aimed to evaluate the association between the HTGW phenotype and the risk of acute pancreatitis with a nationwide population-based cohort. DESIGN: A retrospective, nationwide cohort study. SETTING: Registry of health check-up result from Korean National Health Insurance Service. PARTICIPANTS: A total of 3 912 551 adults who underwent health checkups under the National Health Insurance Service in 2009 were enrolled in this study. INTERVENTIONS: Subjects with both increased waist circumference (WC) and elevated blood triglyceride concentrations were defined as the HTGW phenotype. The participants were divided into four groups, classified as NWNT (normal WC-normal triglycerides), EWNT (elevated WC-normal triglycerides), NWET (normal WC-elevated triglycerides) and HTGW. The WC triglyceride index (WTI) is a quantitative indicator of the HTGW phenotype which is calculated by multiplying WC (cm) by triglyceride levels (mmol/L). PRIMARY OUTCOME MEASURE: The subjects were followed until 31 December 2018. The adjusted HRs of acute pancreatitis in each group were estimated. RESULTS: During the follow-up, there were a total of 8933 of acute pancreatitis occurrences. The incidence of acute pancreatitis in all subjects was 0.278 per 1000 person-year. The HTGW group had the highest incidence (0.444), followed by the NWET (0.381), and EWNT (0.316) groups. The HTGW group had a significant higher incidence of acute pancreatitis than the NWNT groups (HR 1.364 (95% CI 1.279 to 1.454)). The risk of acute pancreatitis steadily increased as the WTI increased (HR 1.847 (95% CI 1.657 to 2.058) in 10th decile). CONCLUSIONS: The HTGW phenotype is confirmed to be an independent risk factor that increases the risk of acute pancreatitis.

Association between white blood cell count and adverse pregnancy outcomes: a retrospective cohort study from a tertiary hospital in China.

OBJECTIVES: This study aimed to clarify the relationship between white blood cell (WBC) and adverse pregnancy outcomes. DESIGN: A total of 25 270 pregnant women underwent peripheral blood white blood cell count tests in the first, second and third trimesters. Adverse pregnancy outcomes were gestational hypertension, pre-eclampsia, gestational diabetes mellitus, preterm birth, low birth weight, caesarean delivery, macrosomia and fetal distress. Due to acute infectious disease or other diseases, 1127 were excluded. SETTING: Minhang Hospital, China. PARTICIPANTS: A total of 24 143 pregnant women were included in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the adverse pregnancy outcomes. RESULTS: For the 24 143 participants, we calculated adjusted ORs for adverse pregnancy outcomes associated with an increased WBC count. For gestational hypertension, the ORs were 1.18 (95% CI, 1.05 to 1.24) in the first trimester and 1.10 (1.06 to 1.13) in the second trimester; for pre-eclampsia, ORs were 1.14 (95% CI, 1.47 to 1.64) in the first trimester and 1.10 (1.05 to 1.16) in the second trimester; for gestational diabetes mellitus, ORs were 1.06 (95% CI, 1.00 to 1.13) in the first trimester and 1.10 (1.04 to 1.16) in the second trimester; for preterm birth, ORs were 1.12 (95% CI, 1.06 to 1.18) in the first trimester, 1.10 (1.06 to 1.13) in the second trimester and 1.12 (1.09 to 1.15) in the third trimester; for low birth weight, ORs were 1.09 (95% CI, 1.02 to 1.17) in the first trimester, 1.03 (0.99 to 1.08) in the second trimester and 1.12 (1.08 to 1.16) in the third trimester. Significant associations were not observed obviously for caesarean delivery, macrosomia and fetal distress. CONCLUSIONS: Our results indicate strong, continuous associations of maternal WBC count with increased risks of adverse pregnancy outcomes.

Association between triglyceride glucose-related markers and the risk of metabolic-associated fatty liver disease: a cross-sectional study in healthy Chinese participants.

OBJECTIVES: This study aimed to evaluate the performance of the triglyceride glucose (TyG) index and its related markers in predicting metabolic-associated fatty liver disease (MAFLD) in healthy Chinese participants. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at Health Management Department of the Affiliated Hospital of Xuzhou Medical University. PARTICIPANTS: A total of 20 922 asymptomatic Chinese participants (56% men) were enrolled. OUTCOME MEASURES: Hepatic ultrasonography was performed to diagnose MAFLD based on the latest diagnostic criteria. The TyG, TyG-body mass (TyG-BMI) and TyG-waist circumference indices were calculated and analysed. RESULTS: Compared with the lowest quartile of the TyG-BMI, the adjusted ORs and 95% CIs for MAFLD were 20.76 (14.54 to 29.65), 92.33 (64.61 to 131.95) and 380.87 (263.25 to 551.05) in the second, third and fourth quartiles, respectively. According to the subgroup analysis, the TyG-BMI in the female and the lean groups (BMI<23 kg/m2) showed the strongest predictive value, with optimal cut-off values for MAFLD of 162.05 and 156.31, respectively. The areas under the receiver operating characteristic curves in female and lean groups were 0.933 (95% CI 0.927 to 0.938) and 0.928 (95% CI 0.914 to 0.943), respectively, with 90.7% sensitivity and 81.2% specificity in female participants with MAFLD and 87.2% sensitivity and 87.1% specificity in lean participants with MAFLD. The TyG-BMI index demonstrated superior predictive ability for MAFLD compared with other markers. CONCLUSIONS: The TyG-BMI is an effective, simple and promising tool for predicting MAFLD, especially in lean and female participants.

Changes in weight, body composition and metabolic parameters after switch to dolutegravir/lamivudine compared with continued treatment with dolutegravir/abacavir/lamivudine for virologically suppressed HIV infection (The AVERTAS trial): a randomised, open-label, superiority trial in Copenhagen, Denmark.

INTRODUCTION: With longer life expectancy in people living with HIV (PLWH) on antiretroviral therapy, cardiovascular disease (CVD) has become a common cause of mortality among them. Abacavir has been associated with an increased risk of myocardial infarction, but the mechanism is unknown. Additionally, abacavir may be obesogenic which could mediate an additional risk factor of CVD. We aim to investigate if discontinuation of abacavir will have a favourable impact on body weight and cardiac parameters in PLWH. METHODS AND ANALYSIS: Randomised, controlled, superiority trial of virologically suppressed PLWH on dolutegravir, abacavir and lamivudine (DTG/ABC/3TC) for ≥6 months. In total, 70 PLWH will be randomised 1:2 to either continue DTG/ABC/3TC or to switch to dolutegravir and lamivudine (DTG/3TC) providing the power of 80% at alpha 5% to detect a mean difference in weight change of 2 kg (Δ) given an SD of 2.7 kg. Follow-up will be 48 weeks. Data will be collected at baseline and week 48. Primary outcome will be change in mean body weight from baseline to week 24 and 48 evaluated in a linear mixed model. Secondary outcomes will be changes in cardiac, inflammatory and metabolic parameters, fat distribution, coagulation, endothelial, platelet function, quality of life and virological control from baseline to week 48. Measurements include CT of thorax and abdomen, external carotid artery ultrasound, liver elastography and dual energy X-ray absorptiometry and blood analysis. Plasma HIV RNA will be measured at baseline, week 4, 24 and 48. Forty participants (20 from each arm) will be included in a substudy involving cardiac MRI at baseline and week 48. Twenty non-HIV-infected controls will be included with a single scan to compare with baseline scan data. ETHICS AND DISSEMINATION: Result from this study will lead to a better understanding of the association between antiretroviral therapy and the impact on weight and risk of CVD. Findings will be useful for both clinicians and PLWH in the guidance of a more individualised HIV treatment. Results from the main study and the substudies will be submitted for publication in a peer-reviewed journal(s). The AVERTAS study is approved by the Ethics Committee of the Capital Region, Denmark (H-20011433), Danish Medicines Agency (EudraCT no. 2019-004999-19) and Regional Data Protection Centre (P-2020-207). TRIAL REGISTRATION NUMBER: Pre-results registration at ClinicalTrials.gov Identifier: NCT04904406, registered 27 May 2021. PROTOCOL VERSION: Protocol version 9.0, 4 April 2023, approved 10-05-2023 by Ethics Committee of the Capital Region, Denmark (H-20011433). Danish Medicines Agency (EudraCT no. 2019-004999-19). Regional Data Protection Centre (P-2020-207) ClinicalTrials.gov.

Nissen-Sleeve procedure versus laparoscopic Roux-en-Y gastric bypass in patients with morbid obesity and gastro-oesophageal reflux disease: protocol for a non-inferiority randomised trial (GINSBY).

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are the most frequently performed procedures in bariatric surgery. In patients with morbid obesity and gastro-oesophageal reflux disease (GORD), LRYGB is the most accepted procedure. For patients with a contraindication for LRYGB or a strong preference for LSG, the Nissen-Sleeve procedure may be a viable new option. The aim of this study is to compare effectiveness of Nissen-Sleeve with LRYGB. METHOD AND ANALYSIS: This is a single-centre, phase III, parallel-group randomised controlled trial in a high-volume bariatric centre in the Netherlands. A total of 88 patients with morbid obesity and GORD will be randomised to evaluate non-inferiority of Nissen-Sleeve versus LRYGB (non-inferiority margin 15%, power 80%, one-sided α 0.025, 9% drop out). Patients with morbid obesity aged 18 years and older with GORD according to the Montreal definition will be included after obtaining informed consent. Exclusion criteria are achalasia, neoplastic abnormalities diagnosed during endoscopy, super obesity (body mass index ≥50 kg/m2), Crohn's disease and medical history of major abdominal surgery. After randomisation, all patients will undergo an upper gastrointestinal endoscopy. Patients in the Nissen-Sleeve arm will undergo a timed barium oesophagram to exclude oesophageal motility disorders. Patients will complete six questionnaires at baseline and every year until 5 years of follow-up. At day 1 postoperative, patients in the Nissen-Sleeve arm will undergo a swallow X-ray to confirm passage. At 1 year, all patients will undergo another endoscopy. The primary outcome is GORD status. Absence of GORD is defined as <8 points on the GORD questionnaire. Secondary outcome measures are long-term GORD improvement; failure rate of procedure; health-related quality of live; weight loss; proton pump inhibitor use; postoperative complications <30 days and >30 days; length of hospital stay; duration of primary surgery; effect on comorbidities; presence and grade of oesophagitis (grade A-D) and/or presence of Barrett's oesophagus and cost-effectiveness. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Research Ethics Committees United (MEC-U), Nieuwegein, on 15 September 2021. Written informed consent will be obtained for all participants in the study. The study results will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NL9789; The Netherlands Trial Registry.

Intravenous ferric derisomaltose in iron-deficient patients undergoing transcatheter aortic valve implantation due to severe aortic stenosis: study protocol of the randomised controlled IIISAS trial.

INTRODUCTION: Iron deficiency is a prevalent comorbidity in patients with severe aortic stenosis and may be associated with procedural and clinical outcomes after transcatheter aortic valve implantation (TAVI). In the Intravenous Iron Supplement for Iron Deficiency in Patients with Severe Aortic Stenosis (IIISAS) trial, we aim to examine whether a single administration of ferric derisomaltose can improve physical capacity after TAVI. METHODS AND ANALYSIS: This randomised, double-blind, placebo-controlled trial aims to enrol 150 patients with iron deficiency who are scheduled for TAVI due to severe aortic stenosis. The study drug and matching placebo are administered approximately 3 months prior to TAVI, and the patients are followed for 3 months after TAVI. Inclusion criteria are iron deficiency, defined as serum ferritin<100 µg/L or ferritin between 100 and 300 µg/L in combination with a transferrin saturation<20% and written informed consent. Exclusion criteria include haemoglobin<10 g/dL, red blood cell disorders, end-stage kidney failure, intolerance to ferric derisomaltose, and ongoing infections. The primary endpoint is the baseline-adjusted distance walked on a 6 min walk test (6MWT) 3 months after TAVI. Secondary end points include quality of life, New York Heart Association functional class (NYHA functional class), and skeletal muscle strength. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Regional Committee for Medical and Health Research of South-Eastern Norway and The Norwegian Medicines Agency. Enrolment has begun, and results are expected in 2022. The results of the IIISAS trial will be disseminated by presentations at international and national conferences and by publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04206228.

Effects of an integrated mobile health lifestyle intervention among overweight and obese women planning for pregnancy in Singapore: protocol for the single-arm healthy early life moments in Singapore (HELMS) study.

INTRODUCTION: Changes in social and lifestyle factors have led to increasing rates of metabolic and mental health problems. We hypothesise that a transformation of the current maternal and child health system is required to deliver interventions that effectively promote a good start to life in populations at risk of metabolic and mental health problems. We describe a single-arm implementation study 'Healthy Early Life Moments in Singapore', which aims to examine whether an integrated lifestyle intervention initiated at preconception and continuing throughout pregnancy and postpartum periods can improve the metabolic and mental health of overweight and obese women, and improve early child growth. METHODS AND ANALYSIS: This single-centre implementation trial is conducted at KK Women's and Children's Hospital, Singapore. The trial aims to recruit 500 women, aged 21-40 years with a body mass index of 25-40 kg/m2 who plan to get pregnant, with interventions delivered before conception, until 18 months postdelivery. Primary outcomes comprise pregnancy rate, maternal metabolic and mental health status. Secondary outcomes include maternal reproductive health, pregnancy outcomes and offspring growth. The intervention will be delivered using a mobile health application, to provide anticipatory guidance, raise awareness and guide goal-setting on lifestyle behaviours that include diet, physical activity, mental wellness and sleep hygiene from preconception to postpartum. Women who conceive within 1 year of recruitment will be followed through pregnancy and studied with their infants at six-time points during the first 18 months of life. Questionnaires, anthropometric measurements and multiple biosamples will be collected at each visit. ETHICS AND DISSEMINATION: The study has been approved by the Centralised Institutional Review Board of SingHealth (2021/2247). Written informed consent will be obtained from all participants. The findings will be published in peer-reviewed journals and disseminated to national and international policy makers. TRIAL REGISTRATION NUMBER: NCT05207059.

Association of self-reported snoring and hyperuricaemia: a large cross-sectional study in Chongqing, China.

OBJECTIVE: To examine the relationship between self-reported snoring and hyperuricaemia in a large-scale population in Chongqing, China. SETTING: Face-to-face electronic questionnaire survey, physical examination and biological sample testing were conducted in 13 districts of Chongqing. Chongqing is a municipality in southwest China. PARTICIPANTS: In this study, 23 308 Han ethnicity permanent residents aged 30-79 years were recruited. Individuals missing data were excluded, 22 389 subjects were included in final analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Serum uric acid (UA) was measured using an oxidase method. Hyperuricaemia was defined as serum UA >420 µmol/L in men and >360 µmol/L in women. Information about self-reported snoring was obtained by questionnaire survey. All participants were divided into 'no snoring' 'snoring occasionally' and 'snoring frequently'. Multivariable logistic regression analysis was performed to assess the relationship between self-reported snoring and hyperuricaemia. RESULTS: The prevalence of hyperuricaemia was 14.43%, and snorers were more likely to have hyperuricaemia than non-snorer in different age and gender groups. For the total population, those who snore occasionally or frequently were more likely to be hyperuricaemia (OR 1.19, 95% CI 1.07 to 1.31; OR 1.33, 95% CI 1.19 to 1.47) compared with no snoring people. Stratification by age, gender and body mass index (BMI), we found that the positive association between snoring frequently and hyperuricaemia was insisted in different age, gender and high BMI groups, and the strength of association varied with different age, gender and BMI category. CONCLUSION: Snoring frequency was positively associated with higher risk of hyperuricaemia. Snoring frequently may be a signal for hyperuricaemia, especially for women, those over 59 years of age, or those who are overweight or obese.

Epidemiology of iron deficiency among adolescents aged 10-19 years old in Qatar: a cross-sectional study.

OBJECTIVE: To estimate the magnitude and the determinants of iron deficiency among adolescents aged 10-19 years in the State of Qatar. DESIGN: A cross-sectional study design was used to conduct the study. SETTING: Primary healthcare centres covering the three main geographical areas. One health centre was selected randomly from each region catchment areas: Northern, Central and Western. PARTICIPANTS: Four hundred and fifty adolescents aged 10-19 years of all nationalities were enrolled in the study. OUTCOME MEASURES: Serum ferritin cut-off level used to diagnose iron deficiency (<15 µg/L), with normal C reactive protein. RESULTS: The mean age of the participants was 14.00±2.920, and more than half of the participating adolescents were among 10-14 years old age group (56.9%). Fifty-five per cent of the study participants were Non-Qatari, and females consisted of 70.0% of the participants. The prevalence of iron deficiency was 26.4%. Iron deficiency was significantly associated with gender, nationality, attaining menarche and consumption of iron absorption enhancers (citrus fruits and juice). CONCLUSION: Iron deficiency among adolescents is of moderate public health concern in the country, according to the classification of the WHO. The estimated prevalence of iron deficiency was close to what was found in other low-income and middle-income countries; however, it is still behind the developed countries. Gender, attaining menarche and dietary habits are among the important factors that are associated with iron deficiency. Thus, there is a need to coordinate efforts and resources to address this issue by implementing effective strategies at the community and primary healthcare levels.

Inpatient hospitalisation and mortality rate trends from 2004 to 2014 in the USA: a propensity score-matched case-control study of hyperkalaemia.

OBJECTIVE: To study the trends of hyperkalaemia in USA inpatient hospitalisation records with heart failure (HF), chronic kidney disease (CKD), acute kidney injury (AKI) and/or type II diabetes mellitus (T2DM) from 2004 to 2014 with respect to prevalence and inpatient mortality. DESIGN: Observational cross-sectional and propensity score-matched case-control study. SETTING: The National Inpatient Sample (representing up to 97% of inpatient hospital discharge records in the USA) from 2004 to 2014 PARTICIPANTS: 120 513 483 (±2 312 391) adult inpatient hospitalisation records with HF, CKD/end-stage renal disease (ESRD), AKI and/or T2DM. EXPOSURE: Hyperkalaemia, defined as the presence of an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of '276.7' in any of the first 15 diagnostic codes. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcomes of interest are the annual rates of hyperkalaemia prevalence and inpatient mortality. RESULTS: Among 120 513 483 (±2 312 391) adult inpatient hospitalisations with HF, CKD/ESRD, AKI and/or T2DM, we found a 28.9% relative increase of hyperkalaemia prevalence from 4.94% in 2004 to 6.37% in 2014 (p<0.001). Hyperkalaemia was associated with an average of 4 percentage points higher rate of inpatient mortality (1.71 post-matching, p<0.0001). Inpatient mortality rates decreased from 11.49%±0.17% to 6.43%±0.08% and 9.67%±0.13% to 5.05%±0.07% for matched cases with and without hyperkalaemia, respectively (p<0.001). CONCLUSIONS: Hyperkalaemia prevalence increased over time and was associated with greater inpatient mortality, even after accounting for presentation characteristics. We detected a decreasing trend in inpatient mortality risk, regardless of hyperkalaemia presence.

Does chronic hyperglycaemia increase the risk of kidney stone disease? results from a systematic review and meta-analysis.

DESIGN: Systematic review and meta-analysis of observational studies was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies reporting on diabetes mellitus (DM) or metabolic syndrome (MetS) and kidney stone disease (KSD). OBJECTIVE: To examine the association between chronic hyperglycaemia, in the form of DM and impaired glucose tolerance (IGT) in the context of MetS and KSD. SETTING: Population-based observational studies. Databases searched: Ovid MEDLINE without revisions (1996 to June 2018), Cochrane Library (2018), CINAHL (1990 to June 2018), ClinicalTrials.gov, Google Scholar and individual journals including the Journal of Urology, European Urology and Kidney International. PARTICIPANTS: Patients with and without chronic hyperglycaemic states (DM and MetS). MAIN OUTCOME MEASURES: English language articles from January 2001 to June 2018 reporting on observational studies. EXCLUSIONS: No comparator group or fewer than 100 patients. Unadjusted values were used for meta-analysis, with further meta-regression presented as adjusted values. Bias was assessed using Newcastle-Ottawa scale. RESULTS: 2340 articles were screened with 13 studies included for meta-analysis, 7 DM (three cohort) and 6 MetS. Five of the MetS studies provided data on IGT alone. These included: DM, n=28 329; MetS, n=31 767; IGT, n=12 770. CONTROLS: DM, n=5 89 791; MetS, n=1 78 050; IGT, n=2 93 852 patients. Adjusted risk for DM cohort studies, RR=1.23 (0.94 to 1.51) (p<0.001). Adjusted ORs for: DM cross-sectional/case-control studies, OR=1.32 (1.21 to 1.43) (p<0.001); IGT, OR=1.26 (0.92 to 1.58) (p<0.0001) and MetS, OR=1.35 (1.16 to 1.54) (p<0.0001). There was no significant difference between IGT and DM (cross-sectional/case-control), nor IGT and MetS. There was a moderate risk of publication bias. Statistical heterogeneity remained significant in adjusted DM cohort values and adjusted IGT (cross-sectional/case-control), but non-signficant for adjusted DM (cross-sectional/case-control). CONCLUSION: Chronic hyperglycaemia increases the risk of developing kidney stone disease. In the context of the diabetes pandemic, this will increase the burden of stone related morbidity and mortality. PROSPERO REGISTRATION NUMBER: CRD42018093382.

Does non-invasive ventilation change metabolic markers in children with obstructive sleep apnoea? A systematic review and meta-analysis study protocol.

INTRODUCTION: Obstructive sleep apnoea (OSA) is not only common within paediatrics but is associated with critical childhood metabolic morbidity such as obesity, cardiovascular disease and glucose tolerance impairment. Increasing evidence suggests an association between childhood OSA and metabolic syndrome such as markers of cardiovascular disease, systemic hypertension, glucose intoleranceand increased lipid profile. Recent studies have targeted changes in metabolic markers in children using non-invasive ventilation (NIV) but no systematic reviews are available to summarise this emerging evidence. The purpose of this systematic review is to provide systematic synthesis of the evidence on the effect of NIV use on metabolic markers in children with OSA. METHODS AND ANALYSIS: A systematic search of electronic databases and grey literature will include paediatric interventional studies (random controlled trials, cohort studies) with and without a comparison group. Two reviewers will independently undertake the two step process of title/abstract and full-text screening. Data will be extracted and assessed, with aggregate data being reported. When the data allow, meta-analysis will be performed. ETHICS AND DISSEMINATION: There are no ethical concerns with this systematic review, as data have previously been published. This review will inform clinicians taking care of children with OSA and obesity/metabolic syndrome about the potential effects of NIV therapies on metabolic markers and has the potential to change the approach to childhood OSA and obesity. Results of this systematic review will be submitted for dissemination in abstract and manuscript form.

Does supplementation with carnosine improve cardiometabolic health and cognitive function in patients with pre-diabetes and type 2 diabetes? study protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Carnosine, an over-the-counter food supplement, has a promising potential for the prevention and treatment of chronic diseases such as type 2 diabetes (T2DM), cardiovascular and neurodegenerative diseases through its anti-inflammatory, antiglycation, antioxidative and chelating effects. We have previously shown that supplementation with carnosine preserves insulin sensitivity and secretion in non-diabetic overweight and obese individuals. The effect of carnosine on cardiometabolic risk and related cognitive outcomes in patients with pre-diabetes and T2DM has thus far not been studied. We therefore aim to investigate whether supplementation with carnosine improves cardiometabolic health and cognitive function in patients with pre-diabetes and T2DM. METHODS AND ANALYSIS: We will employ a parallel design randomised controlled trial. Fifty participants with pre-diabetes (impaired fasting glycaemia and impaired glucose tolerance) and T2DM (with HbA1c level < 8%) aged between 18 to 70 years will be randomly assigned to the intervention or control group. At baseline, participants will undergo a medical review and series of tests including anthropometric measurements (body mass index, a dual X-ray absorptiometry and peripheral quantitative computed tomography scan), an oral glucose tolerance test, cardiovascular measurements (central blood pressure, endothelial function and arterial stiffness), cognitive function, physical activity measurement, heart rate variability and liver fibroscan as well as questionnaires to assess dietary habits, sleep quality, depression and quality of life. The intervention group will receive 2 g of carnosine daily in two divided doses while the control group will receive identical placebo capsules for 14 weeks. All baseline measurements will be repeated at the end of the intervention. The change in glycaemic, cardiovascular and cognitive parameters as well as other measures will be compared between the groups. ETHICS AND DISSEMINATION: This study is approved by the Human Research Ethics Committee of Monash Health and Monash University, Australia. The findings will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION: NCT02917928; Pre-results.