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.

Understanding the GERD Barrier.

Gastroesophageal reflux disease (GERD) is steadily increasing in incidence and now affects 18% to 28% of the population in the United States. A thorough understanding of the pathophysiology underlying this disease is necessary to improve the current standard of care. Most GERD pathophysiology models focus on the lower esophageal sphincter (LES) as the key element which prevents esophageal reflux. More recent research has highlighted the crural diaphragm (CD) as an additional critical component of the GERD barrier. We now know that the CD actively relaxes when the distal esophagus is distended and contracts when the stomach is distended. Crural myotomy in animal models increases esophageal acid exposure, highlighting the CD's vital role. There are also multiple physiological studies in patients with symptomatic hiatal hernia that demonstrate CD dysfunction is associated with GERD. Finally, computer models integrating physiological data predict that the CD and the LES each contribute roughly 50% to the GERD barrier. This more robust understanding has implications for future procedural management of GERD. Specifically, effective GERD management mandates repair of the CD and reinforcement of the LES. Given the high rate of hiatal hernia recurrences, it seems that novel antireflux procedures should target this essential component of the GERD barrier. Future research should focus on methods to maintain crural integrity, decrease hiatal hernia recurrence, and improve long-term competency of the GERD barrier.

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.

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.

Development of a multivariable risk model integrating urinary cell DNA methylation and cell-free RNA data for the detection of significant prostate cancer.

BACKGROUND: Prostate cancer exhibits severe clinical heterogeneity and there is a critical need for clinically implementable tools able to precisely and noninvasively identify patients that can either be safely removed from treatment pathways or those requiring further follow up. Our objectives were to develop a multivariable risk prediction model through the integration of clinical, urine-derived cell-free messenger RNA (cf-RNA) and urine cell DNA methylation data capable of noninvasively detecting significant prostate cancer in biopsy naïve patients. METHODS: Post-digital rectal examination urine samples previously analyzed separately for both cellular methylation and cf-RNA expression within the Movember GAP1 urine biomarker cohort were selected for a fully integrated analysis (n = 207). A robust feature selection framework, based on bootstrap resampling and permutation, was utilized to find the optimal combination of clinical and urinary markers in a random forest model, deemed ExoMeth. Out-of-bag predictions from ExoMeth were used for diagnostic evaluation in men with a clinical suspicion of prostate cancer (PSA ≥ 4 ng/mL, adverse digital rectal examination, age, or lower urinary tract symptoms). RESULTS: As ExoMeth risk score (range, 0-1) increased, the likelihood of high-grade disease being detected on biopsy was significantly greater (odds ratio = 2.04 per 0.1 ExoMeth increase, 95% confidence interval [CI]: 1.78-2.35). On an initial TRUS biopsy, ExoMeth accurately predicted the presence of Gleason score ≥3 + 4, area under the receiver-operator characteristic curve (AUC) = 0.89 (95% CI: 0.84-0.93) and was additionally capable of detecting any cancer on biopsy, AUC = 0.91 (95% CI: 0.87-0.95). Application of ExoMeth provided a net benefit over current standards of care and has the potential to reduce unnecessary biopsies by 66% when a risk threshold of 0.25 is accepted. CONCLUSION: Integration of urinary biomarkers across multiple assay methods has greater diagnostic ability than either method in isolation, providing superior predictive ability of biopsy outcomes. ExoMeth represents a more holistic view of urinary biomarkers and has the potential to result in substantial changes to how patients suspected of harboring prostate cancer are diagnosed.

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.

A four-group urine risk classifier for predicting outcomes in patients with prostate cancer.

OBJECTIVES: To develop a risk classifier using urine-derived extracellular vesicle (EV)-RNA capable of providing diagnostic information on disease status prior to biopsy, and prognostic information for men on active surveillance (AS). PATIENTS AND METHODS: Post-digital rectal examination urine-derived EV-RNA expression profiles (n = 535, multiple centres) were interrogated with a curated NanoString panel. A LASSO-based continuation ratio model was built to generate four prostate urine risk (PUR) signatures for predicting the probability of normal tissue (PUR-1), D'Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer. This model was applied to a test cohort (n = 177) for diagnostic evaluation, and to an AS sub-cohort (n = 87) for prognostic evaluation. RESULTS: Each PUR signature was significantly associated with its corresponding clinical category (P < 0.001). PUR-4 status predicted the presence of clinically significant intermediate- or high-risk disease (area under the curve = 0.77, 95% confidence interval [CI] 0.70-0.84). Application of PUR provided a net benefit over current clinical practice. In an AS sub-cohort (n = 87), groups defined by PUR status and proportion of PUR-4 had a significant association with time to progression (interquartile range hazard ratio [HR] 2.86, 95% CI 1.83-4.47; P < 0.001). PUR-4, when used continuously, dichotomized patient groups with differential progression rates of 10% and 60% 5 years after urine collection (HR 8.23, 95% CI 3.26-20.81; P < 0.001). CONCLUSION: Urine-derived EV-RNA can provide diagnostic information on aggressive prostate cancer prior to biopsy, and prognostic information for men on AS. PUR represents a new and versatile biomarker that could result in substantial alterations to current treatment of patients with prostate cancer.

Resveratrol protects against doxorubicin-induced cardiotoxicity in aged hearts through the SIRT1-USP7 axis.

KEY POINTS: Doxorubicin induced functional deteriorations and elevations of USP7-related apoptotic/catabolic signalling in the senescent heart Resveratrol protects against doxorubicin-induced alterations through the restoration of SIRT1 deacetylase activity ABSTRACT: A compromised cardiac function is often seen in elderly cancer patients receiving doxorubicin therapy. The present study tested the hypothesis that acute intervention with resveratrol, a natural anti-oxidant found in grapes and red wine, reduces the cardiotoxicity of doxorubicin through restoration of sirtuin 1 (SIRT1) deacetylase activity, and attenuation of the catabolic/apoptotic pathways orchestrated by USP7, a p53 deubiquitinating protein, using young (aged 2 months) and old (aged 10 months) senescence-accelerated mice prone 8 (SAMP8). Animals were randomised to receive saline, doxorubicin, and doxorubicin in combination with resveratrol, in the presence or absence of SIRT1 inhibitors, sirtinol or EX527. Resveratrol alone, but not in combination with either of the SIRT1 inhibitors, suppressed the doxorubicin-induced impairment of cardiac systolic function in aged animals. Doxorubicin reduced SIRT1 deacetylase activity, and elevated proteasomal activity and USP7; it also increased the protein level of p300 and ubiquitinated proteins in hearts from aged SAMP8. These doxorubicin-induced alterations were prevented by resveratrol, whereas the protective action of resveratrol was antagonised by sirtinol and EX527. In young SAMP8 hearts, resveratrol attenuated the doxorubicin-induced increases in acetylation of Foxo1 and transactivation of MuRF-1, whereas these mitigations were not found after treatment with SIRT1 inhibitors. However, the protein contents of acetylated Foxo1 and MuRF-1 were not affected by any of the drugs studied in aged SAMP8 hearts. Resveratrol also ameliorated the augmentation of pro-apoptotic markers including p53, Bax, caspase 3 activity and apoptotic DNA fragmentation induced by doxorubicin in hearts from aged animals, whereas these reductions were diminished by combined treatment with SIRT1 inhibitors. These data demonstrate that resveratrol ameliorates doxorubicin-induced cardiotoxicity in aged hearts through the restoration of SIRT1 activity to attenuate USP7-related catabolic/pro-apoptotic signalling.

Unacylated ghrelin restores insulin and autophagic signaling in skeletal muscle of diabetic mice.

Impairment of insulin signaling in skeletal muscle detrimentally affects insulin-stimulated disposal of glucose. Restoration of insulin signaling in skeletal muscle is important as muscle is one of the major sites for disposal of blood glucose. Recently, unacylated ghrelin (UnAG) has received attention in diabetic research due to its favorable actions on improving glucose tolerance, glycemic control, and insulin sensitivity. The investigation of UnAG has entered phase Ib clinical trial in type 2 diabetes and phase II clinical trial in hyperphagia in Prader-Willi syndrome. Nonetheless, the precise mechanisms responsible for the anti-diabetic actions of UnAG remain incompletely understood. In this study, we examined the effects of UnAG on restoring the impaired insulin signaling in skeletal muscle of db/db diabetic mice. Our results demonstrated that UnAG effectively restored the impaired insulin signaling in diabetic muscle. UnAG decreased insulin receptor substrate (IRS) phosphorylation, increased protein kinase B (Akt) phosphorylation, and, hence, suppressed mTOR signaling. Consequently, UnAG enhanced Glut4 localization and increased PDH activity in the diabetic skeletal muscle. Intriguingly, our data indicated that UnAG normalized the suppressed autophagic signaling in diabetic muscle. In conclusion, our findings illustrated that UnAG restored the impaired insulin and autophagic signaling in skeletal muscle of diabetic mice, which are valuable to understand the underlying mechanisms of the anti-diabetic action of UnAG at peripheral skeletal muscle level.

A review of the management of positive biochemical screening for phaeochromocytoma and paraganglioma: a salutary tale.

BACKGROUND: Phaeochromocytomas (PC) and paragangliomas (PGL) are rare neuroendocrine tumours of chromaffin cells. Diagnosis depends on biochemical evidence of excessive production of catecholamines. This is straightforward when test results are orders of magnitude above the concentrations expected in healthy individuals and those with essential hypertension. Equivocal results pose a management dilemma. AIM: We reviewed biochemical screens that were positive and the ensuing management for PC/PGL at our institution. The objective was to inform the development of a standardised approach to investigation and clinical follow-up. METHOD: All records of positive biochemical screening for PC/PGL were extracted from the laboratory information system between January 2004 and June 2012. Clinical notes of patients with positive results were reviewed. RESULTS: A total of 2749 biochemical screens were performed during the evaluation period. Of these, 106 (3.9%) performed on 82 patients were positive. Chart review determined that 12/82 patients had histologically confirmed PC/PG. Of the 70 patients remaining, the most common indication for biochemical screening was hypertension and the medical subspecialty most frequently requesting the test was Endocrinology. The primary team carried out repeat testing on 35/70 (50%) patients and in 29 results normalised. Notably, 35/70 (50%) patients did not have any follow-up of positive test results. CONCLUSION: This study highlights the necessity for a standardised diagnostic protocol for PC/PGL. We suggest that appropriate follow-up of borderline-elevated results should first include repeat biochemical testing. This should be performed under standardised pre-analytical conditions and where possible off all potentially interfering medications, measuring plasma free metadrenalines.

Modified Brain Injury Guidelines for preinjury anticoagulation in traumatic brain injury: An opportunity to reduce health care resource utilization.

INTRODUCTION: The Brain Injury Guidelines (BIG) stratify patients by traumatic brain injury (TBI) severity to provide management recommendations to reduce health care resource burden but mandates that patients on anticoagulation (AC) are allocated to the most severe tertile (BIG 3). We sought to analyze TBI patients on AC therapy using a modified BIG model to determine if this population can offer further opportunity for safe reductions in health care resource utilization. METHODS: Patients 55 years or older on AC with traumatic intracranial hemorrhage (ICH) from two centers were retrospectively stratified into BIG 1 to 3 risk groups using modified BIG criteria excluding AC as a criterion. Intracranial hemorrhage progression, neurosurgical intervention (NSI), death, and worsened discharge status were compared. RESULTS: A total of 221 patients were included, with 23%, 29%, and 48% classified as BIG 1, BIG 2, and BIG 3, respectively. The BIG 3 cohort had a higher rate of AC reversal agents administered (66%) compared with the BIG 1 (40%) and BIG 2 (54%) cohorts ( p < 0.01), as well as ICH progression discovered on repeat head computed tomography (56% vs. 38% vs. 26%, respectively; p < 0.001). No patients in the BIG 1 and 2 cohorts required NSI. No patients in BIG 1 and 3% of patients in BIG 2 died secondary to the ICH. In the BIG 3 cohort, 16% of patients required NSI and 26% died. Brain Injury Guidelines 3 patients had 15 times the odds of mortality compared with BIG 1 patients ( p < 0.01). CONCLUSION: The AC population had higher rates of ICH progression than the BIG literature, but this did not lead to more NSI or mortality in the lower tertiles of our modified BIG protocol. If the modified BIG used the original tertile management on our population, then NS consultation may have been reduced by up to 52%. These modified criteria may be a safe opportunity for further health care resource and cost savings in the TBI population. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Experimental observations of soliton wave trains in electron beams.

The first experimental observation of a Korteweg-de Vries-type soliton wave train in intense electron beams is reported. A narrow, large-amplitude perturbation on a long-pulse beam is observed to steepen and spawn a soliton wave train. The pulse width and amplitude of each peak remain unchanged over a long propagation distance, and the amplitude is inversely proportional to the square of the width. Two such pulses are seen to pass through each other, emerging from the collision unchanged. The experimental results are reproduced by particle-in-cell simulations.

Impact of gender, ethnicity and social deprivation on access to surgical or transcatheter aortic valve replacement in aortic stenosis: a retrospective database study in England.

OBJECTIVE: To assess gender, ethnicity, and deprivation-based differences in provision of aortic valve replacement (AVR) in England for adults with aortic stenosis (AS). METHODS: We retrospectively identified adults with AS from the English Hospital Episode Statistics (HES) between April 2016 and March 2019 and those who subsequently had an AVR. We separately used HES-linked Clinical Practice Research Datalink (CPRD) to identify people with AVR and evaluate the timeliness of their procedure (CPRD-AVR cohort). ORs for AVR in people with an AS diagnosis were estimated using multivariable logistic regression adjusted for age, region and comorbidity. AVR was considered timely if performed electively and without evidence of cardiac decompensation before AVR. RESULTS: 183 591 adults with AS were identified in HES; of these, 31 436 underwent AVR. The CPRD-AVR cohort comprised 10 069 adults. Women had lower odds of receiving AVR compared with men (OR 0.65; 95% CI 0.63 to 0.66); as did people of black (OR 0.70; 95% CI 0.60 to 0.82) or South Asian (OR 0.75; 95% CI 0.69 to 0.82) compared with people of white ethnicities. People in the most deprived areas were less likely to receive AVR than the least deprived areas (OR 0.8; 95% CI 0.75 to 0.86). Timely AVR occurred in 65% of those of white ethnicities compared with 55% of both those of black and South Asian ethnicities. 77% of the least deprived had a timely procedure compared with 58% of the most deprived; there was no gender difference. CONCLUSIONS: In this large, national dataset, female gender, black or South Asian ethnicities and high deprivation were associated with significantly reduced odds of receiving AVR in England. A lower proportion of people of minority ethnicities or high deprivation had a timely procedure. Public health initiatives may be required to increase clinician and public awareness of unconscious biases towards minority and vulnerable populations to ensure timely AVR for everyone.

Gene-Transcript Expression in Urine Supernatant and Urine Cell-Sediment Are Different but Equally Useful for Detecting Prostate Cancer.

There is considerable interest in urine as a non-invasive liquid biopsy to detect prostate cancer (PCa). PCa-specific transcripts such as the TMPRSS2:ERG fusion gene can be found in both urine extracellular vesicles (EVs) and urine cell-sediment (Cell) but the relative usefulness of these and other genes in each fraction in PCa detection has not been fully elucidated. Urine samples from 76 men (PCa n = 40, non-cancer n = 36) were analysed by NanoString for 154 PCa-associated genes-probes, 11 tissue-specific, and six housekeeping. Comparison to qRT-PCR data for four genes (PCA3, OR51E2, FOLH1, and RPLP2) was strong (r = 0.51-0.95, Spearman p < 0.00001). Comparing EV to Cells, differential gene expression analysis found 57 gene-probes significantly more highly expressed in 100 ng of amplified cDNA products from the EV fraction, and 26 in Cells (p < 0.05; edgeR). Expression levels of prostate-specific genes (KLK2, KLK3) measured were ~20× higher in EVs, while PTPRC (white-blood Cells) was ~1000× higher in Cells. Boruta analysis identified 11 gene-probes as useful in detecting PCa: two were useful in both fractions (PCA3, HOXC6), five in EVs alone (GJB1, RPS10, TMPRSS2:ERG, ERG_Exons_4-5, HPN) and four from Cell (ERG_Exons_6-7, OR51E2, SPINK1, IMPDH2), suggesting that it is beneficial to fractionate whole urine prior to analysis. The five housekeeping genes were not significantly differentially expressed between PCa and non-cancer samples. Expression signatures from Cell, EV and combined data did not show evidence for one fraction providing superior information over the other.

B-type natriuretic peptide in the cardiology department.

Heart Failure is one of the fastest growing cardiovascular diseases of the 21st century. Echocardiogram is considered the gold standard for diagnosis, but is costly, time consuming and not readily accessible to all patients. Our aim was to assess the diagnostic utility of BNP to risk stratify patients for ECHO. Seventy-four GP referred, non-pregnant patients of > or = 18 years with a working diagnosis of HF were recruited. Patients were given two appointments to attend the Cardiology Department and at each, were examined by the same cardiologist, had their medications recorded and blood drawn for BNP analysis. ECHO was performed at the second visit. The diagnosis of HF was confirmed in 49 of 74 patients (66%). The clinical utility of BNP to rule-in HF was evaluated using ROC curve analysis. The AUC was satisfactory at 0.691 (C.I. 0.573-0.793). The positive likelihood ratio (+LR) was 5.87, negative likelihood ratio (-LR) was 0.58, the positive predictive value was 92% and a negative predictive value was 47%. One-third of patients (n = 25) had a BNP >178 pg/mL, 23 of whom had HF confirmed. At this decision threshold BNP correctly classified 23 of 25 patients who were confirmed not to have HF (Specificity for HF of 92%). A BNP of > or = 178 pg/mL can be used to prioritise GP patients for ECHO.

Trimester-specific reference intervals for IFCC standardised haemoglobin A(1c): new criterion to diagnose gestational diabetes mellitus (GDM)?

We established trimester-specific reference intervals for IFCC standardised HbA(1c) in 311 non-diabetic Caucasian pregnant women (n = 246) and non-pregnant women (n = 65). A selective screening strategy based on risk factors for gestational diabetes was employed. Pregnancy trimester was defined as trimester 1 (T1, n = 40) up to 12 weeks + 6 days, trimester 2 (T2, n = 106) 13 to 27 weeks + 6 days, trimester 3 (T3, n = 100) > 28 weeks to delivery. The normal HbA(1c) reference interval for Caucasian non-pregnant women was 29-37 mmol/mol (DCCT: 4.8-5.5%), T1: 24-36 mmol/mol (DCCT: 4.3-5.4%), T2: 25-35 mmol/mol (DCCT: 4.4-5.4%), and T3: 28-39 mmol/mol (DCCT: 4.7-5.7%). HbA(1c) was significantly decreased in trimesters 1 (P < 0.01) and 2 (P < 0.001) compared to non-pregnant women. Retrospective application of selective screening to Caucasian women of the Atlantic DIP cohort determined that 5,208 met the criteria. 945 of those women (18.1%) were diagnosed with Gestational Diabetes Mellitus (GDM) using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) glucose concentration thresholds. HbA(1c) measurement within 2 weeks of the diagnostic Oral Glucose Tolerance Test (OGTT) was available in 622 of 945 (66%). Applying the decision threshold for T2: HbA(1c) > 35 mmol/mol (DCCT > 5.4%) identified 287 of 622 (46%) of those with GDM. HbA(1c) measurement in T2 (13 to 27 weeks) should be included in the diagnostic armamentarium for GDM. This would reduce the need for diagnostic OGTT in a significant number of women.

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.