Ploutarchos Tzoulis

Multicentre study of investigation and management of inpatient hyponatraemia in the UK

Purpose Hyponatraemia is associated with significant morbidity and mortality. The objectives of this study were to evaluate the investigation and management of hyponatraemia and to assess the use of different therapeutic modalities and their effectiveness in routine practice. Study design This multicentre, retrospective, observational study was conducted at three acute NHS Trusts in March 2013. A retrospective chart review was performed on the first 100 inpatients with serum sodium (sNa) ≤128 mmol/L during hospitalisation. Results One hundred patients (47 male, 53 female) with a mean±SD age of 71.3±15.4 years and nadir sNa of 123.4±4.3 mmol/L were included. Only 23/100 (23%) had measurements of paired serum and urine osmolality and sodium, while 31% had an assessment of adrenal reserve. The aetiology of hyponatraemia was unrecorded in 58% of cases. The mean length of hospital stay was 17.5 days with an inpatient mortality rate of 16%. At hospital discharge, 53/84 (63.1%) patients had persistent hyponatraemia, including 20/84 (23.8%) with sNa <130 mmol/L. Overall 37/100 (37%) patients did not have any treatment for hyponatraemia. Among 76 therapeutic episodes, the most commonly used treatment modalities were isotonic saline in 38/76 cases (50%) and fluid restriction in 16/76 (21.1%). Fluid restriction failed to increase sNa by >1 mmol/L/day in 8/10 (80%) cases compared with 4/26 (15.4%) for isotonic saline. Conclusions Underinvestigation and undertreatment of hyponatraemia is a common occurrence in UK clinical practice. Therefore, development of UK guidelines and introduction of electronic alerts for hyponatraemia should be considered to improve clinical practice.

Real-life experience of tolvaptan use in the treatment of severe hyponatraemia due to syndrome of inappropriate antidiuretic hormone secretion.

European guidelines do not recommend tolvaptan for treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH), principally owing to concerns about risk of overly rapid correction of hyponatraemia. This study evaluated the real‐life effectiveness and safety of tolvaptan.

Prevalence of Low Bone Mass and Vitamin D Deficiency in β-Thalassemia Major

Abstract Low bone mass, a major cause of morbidity in patients with β-thalassemia major (β-TM), is multifactorial. There is lack of data about the current prevalence of low bone mass in patients with β-TM. The aims of this study are to examine the current prevalence of low bone mass in β-TM patients and the association between demographic characteristics, markers of iron overload, endocrinopathies, glycemic status and bone mineral density (BMD) as well as to study the 25-OH-vitamin D status of the patients and its relationship with BMD. Our institution serves the largest cohort of β-TM patients in the UK. From 99 patients (49 males, 50 females) with a mean ± standard deviation (SD) age of 36 ± 9 years, 55.5% had low BMD for their age as defined by Z-score BMD <−2.0 either at the lumbar spine (43.9%) or at the hip (25.5%). The only statistically significant association on the multivariate analysis was between hypogonadism and low BMD at the lumbar spine. In our study, 29.9% of patients had vitamin D deficiency, 65.7% had vitamin D insufficiency and 12.4% had optimal levels. No association between vitamin D status and low bone mass was found. Our study demonstrated a much lower prevalence of low bone mass in adults with β-TM compared to previous studies. Further studies are needed to examine whether this suggests a widespread improvement across patients with β-TM possibly due to advances in therapeutics. Most patients had suboptimal 25-OH-vitamin D levels, but no association between vitamin D status and bone mass was demonstrated.

History of myocardial iron loading is a strong risk factor for diabetes mellitus and hypogonadism in adults with β thalassemia major

Endocrinopathies are common complications of transfusional hemosiderosis among patients with β thalassemia major (TM). Previous studies had shown associations between some endocrinopathies and iron overload of the myocardium, liver and/or endocrine organs as assessed by MRI techniques. This retrospective analysis of 92 patients with TM (median age 36 yr) from a tertiary adult thalassemia unit in UK aimed to determine independent risk factors associated with endocrinopathies among these patients. Unlike previous studies, longitudinal data on routine measurements of iron load [worst myocardial and liver T2* values since 1999, worst LIC by MRI‐R2 since 2008 and average 10‐yr serum ferritin (SF)] up to April 2010 together with demographic features and age of initiating chelation were analyzed for associations with endocrinopathies. The most common endocrinopathies in this cohort were hypogonadism (67%) and diabetes mellitus (DM) (41%), and these were independently associated with myocardial T2* <20 ms (P < 0.001 and P = 0.008, respectively) and increased age (P = 0.002 and P = 0.016, respectively). DM and hypogonadism were independently associated with average SF >1250 μg/L (P = 0.003) and >2000 μg/L (P = 0.047), respectively. DM was also associated with initial detection of abnormal myocardial T2* at an older age (30 yr vs. 24 yr, P = 0.039). An abnormal myocardial T2* may therefore portend the development of DM and hypogonadism in patients with TM.

Joint diabetes thalassaemia clinic: an effective new model of care.

Abstract Diabetes is a significant complication of β-thalassemia major (β-TM) and most patients receive fragmented diabetes care. In 2005, we developed a unique Joint Diabetes Thalassaemia Clinic, based at the Department of Diabetes, Whittington Health, London, UK, where patients were reviewed jointly by a multidisciplinary team, including Consultant Diabetologist and Hematologist. Study of the Joint Diabetes Thalassaemia Clinic (2005–2009) showed improvement in glycemic control with fructosamine reduction from 344 umol/L to 319 umol/L over a 1-year period as well as improvement in lipid profiles. The proportion of patients attending the Joint Clinic who achieved metabolic targets compared to the National Diabetes Audit for England was higher for glycemic control (73.0 Joint Diabetes Thalassaemia Clinic vs. 63.0% nationally), blood pressure control (58.0 Joint Diabetes Thalassaemia Clinic vs. 30.0% nationally) and cholesterol control (81.0 Joint Diabetes Thalassaemia Clinic vs. 78.0% nationally). Five patients (22.7%) had microvascular complications. A significant proportion of our patients had endocrinopathies (86.0% hypogonadism, 18.0% hypothyroidism, 23.0% hypoparathyroidism). The unique partnership of our Joint Diabetes Thalassaemia Clinic, allowed these very complex patients to be managed effectively.

Investigation of inpatient hyponatraemia in a teaching hospital

Investigations Nadir sNa Nadir sNa RR P value ≤125 126-128 N=87 N=52 Volume status 73.6% 42.3% 1.74 <0.001 Serum osmo 52.9% 13.5% 4.53 <0.001 Urine osmo 50.6% 15.4% 3.28 <0.001 Urine Na 47.1% 15.4% 3.06 <0.001 Paired osmo-Na 40.2% 9.1% 4.18 <0.001 Serum TFTs 70.1% 46.2% 1.51 0.007 Serum cortisol 45.6% 7.7% 5.97 <0.001 Endocrine input 17.2% 9.1% 1.79 0.318 This retrospective, single-centre study included all inpatients with serum sodium (sNa) ≤128 mmol/l at any point during hospitalisation over a 3-month period.