Evaluation of the diagnostic performance of the creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation in people with diabetes: A systematic review.

AIMS: GFR estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr ) equation is used to screen for diabetic kidney disease and assess its severity. We systematically reviewed the process and outcome of evaluating CKD-EPICr in estimating point GFR or GFR decline over time in adults with type 1 or type 2 diabetes. METHODS: In this systematic review, MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched up to August 2019. Observational studies comparing CKD-EPICr with measured GFR (mGFR) in adults with diabetes were included. Studies on people with kidney transplant, non-diabetes related kidney disease, pregnancy, potential kidney donors, and those with critical or other systematic illnesses were excluded. Two independent reviewers extracted data from published papers and disagreements were resolved by consensus. Risk-of-bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. (PROSPERO registration number: CRD42018108776). RESULTS: From the 2820 records identified, 29 studies (14 704 participants) were included. All studies were at risk of bias. Bias (eight different forms) ranged from -26 to 35 ml min-1  1.73 m-2 ; precision (five different forms) ranged between 9 and 63 ml min-1  1.73 m-2 ; accuracy (five different forms) ranged between 16% and 96%; the correlation coefficient between CKD-EPICr and mGFR (four different forms) ranged between 0.38 and 0.86; and the reduced major axis regression slope ranged between 0.8 and 1.8. CONCLUSIONS: Qualitative synthesis of data suggested CKD-EPICr was inaccurate in estimating point GFR or GFR decline over time. Furthermore, a lack of consistency in the methods and processes of evaluating the diagnostic performance of CKD-EPICr limits reliable quantitative assessment. The equation needs to be improved in adults with diabetes.

Systematic review and meta-analysis of prevalence of sarcopenia in post acute inpatient rehabilitation.

Sarcopenia is associated with poor function and increased risk of falls and disability. This work reports a systematic review and meta-analysis of prevalence of sarcopenia in post acute inpatient rehabilitation. Sarcopenia is found to be present in approximately 50% of rehabilitation patients and its prevalence may vary with admission diagnosis. PURPOSE: To conduct a systematic review and meta-analysis of reported prevalence of sarcopenia in post acute inpatient rehabilitation. METHODS: Systematic review conducted according to PRISMA guidelines (PROSPERO registration number CRD42016054135). Databases searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register, and CINAHL. Studies considered the following: published January 1988-February 2017. Key terms are as follows: "sarcopenia" AND "inpatient rehabilitation" OR "rehabilitation" AND/OR "prevalence". Abstracts and subsequently full studies reporting sarcopenia prevalence in adults admitted to rehabilitation reviewed irrespective of design, provided sarcopenia diagnosis included at least assessment of muscle mass. Random effect meta-analysis was conducted. Methodological quality assessment: Agency for Healthcare Research and Quality, US Department of Health and Human Services tool (MORE tool); Joanna Briggs Institute Prevalence Critical Appraisal Tool. RESULTS: Four hundred twenty-six studies identified during initial search, 399 excluded after reviewing titles and abstracts, 21 full text articles reviewed, and six studies met inclusion criteria. Patient populations: after hip fracture (five studies), general deconditioning (one study). Identified sarcopenia prevalence ranged from 0.28 to 0.69. Pooled sarcopenia prevalence obtained with random effect meta-analysis: 0.56 (95% CI 0.46-0.65), heterogeneity I2 = 92.9%. Main quality shortcomings: lack of reporting of inter- and intra-rater reliability, lack of generalizability to other rehabilitation populations. CONCLUSIONS: Original research examining sarcopenia prevalence in inpatient rehabilitation is scarce. Patient populations studied to date are not representative of general rehabilitation population with regard to both age and admission diagnoses. Sarcopenia may be present in approximately half of rehabilitation patients and its prevalence may vary with admission diagnosis.

A longitudinal study of thyroid autoantibodies in pregnancy: the importance of test timing.

OBJECTIVE: Thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TGAb) are frequently measured to investigate thyroid dysfunction in pregnancy. Despite the recognized fall of these autoantibodies in pregnancy, there is limited guidance on the timing of such testing. We assessed optimal test timing of TPOAb/TGAb for the detection of Hashimoto's thyroiditis and post-partum thyroid dysfunction (PPTD). DESIGN: Prospective longitudinal study with recruitment in Trimester 1. PATIENTS: Healthy women ≤13 weeks' gestation from Mercy Hospital for Women, a tertiary obstetric hospital in Melbourne. MEASUREMENTS: Serum TPOAb, TGAb, TSH and fT4 were measured at Trimester 1 (T1), Trimester 2(T2), Trimester 3(T3) and postpartum (PP) in each participant. Post-partum thyroid dysfunction (PPTD) was defined if TSH deviated from the assay's nonpregnant reference interval. Longitudinal random-effect logistic regression was used to investigate the association between time and positive/negative thyroid autoantibody status. RESULTS: Samples from 140 women at T1 (12·0: 10·3-13·0) (median: IQR weeks' gestation); 95 at T2 (24·3: 23·0-25·9), 79 at T3 (35·9: 34·8-36·7) and 83 at PP (12·4: 10·8-14·6 weeks post-partum) were attained. At T1, 13 (9%) and 15 (11%) women had positive TPOAb and TGAb, respectively. The odds of having a positive TPOAb were 96% lower at T2 [OR = 0·04 (95% CI: 0·02-0·8; P = 0·03)] and 97% lower at T3 [OR = 0·03 (95% CI: 0·001-0·6; P = 0·02)] than at T1. Similarly, the odds of having a positive TGAb were 99·4% lower [OR = 0·006 (95% CI: 0-0·3; P = 0·01)] at T2, and 99·5% lower [OR = 0·005 (95% CI: 0-0·4; P = 0·02)] at T3 than at T1. The ROC analysis diagnostic ORs for a positive TPOAb and/or TGAb to predict PPTD were 7·8 (95% CI: 2·2-27·6), 1·2 (95% CI: 0-8·9), 2·0 (95% CI: 0-16·8), and 12·2 (95% CI: 3·3-44·9) at T1, T2, T3 and post-partum, respectively. CONCLUSIONS: A significant proportion of pregnant women lose their thyroid autoantibody positivity after T1. The gestation-dependent loss of TPOAb/TGAb positivity and reduction in diagnostic accuracy for predicting PPTD limits the value of testing at T2 and T3.

Performance of formulas for estimating glomerular filtration rate in Indigenous Australians with and without Type 2 diabetes: the eGFR Study.

AIMS: It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. METHODS: Indigenous Australians with (n = 224) or without (n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). RESULTS: The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min(-1)  1.73 m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min(-1)  1.73 m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min(-1)  1.73 m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). CONCLUSIONS: The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.

Liver transplantation for the treatment of homozygous familial hypercholesterolaemia in an era of emerging lipid-lowering therapies.

Homozygous familial hypercholesterolaemia (FH) causes severe premature coronary artery disease because of very high levels of low density lipoprotein (LDL)-cholesterol. Standard lipid-lowering drugs and LDL-apheresis may not be sufficiently effective. Liver transplantation replaces defective LDL receptors and vastly improves the lipid profile, and we present the first report of an Australian adult to receive this treatment. Emerging drug treatments for FH may be alternatives to LDL-apheresis and transplantation, but long-term safety and efficacy data are lacking for all of these options.

Salt supplementation blunts the blood pressure response to telmisartan with or without hydrochlorothiazide in hypertensive patients with type 2 diabetes.

AIMS/HYPOTHESIS: We assessed the effects of sodium chloride (NaCl) supplementation on the blood pressure response to treatment with telmisartan with or without hydrochlorothiazide in hypertensive patients with type 2 diabetes and habitually high (HDS, sodium excretion >200 mmol/24 h on two out of three consecutive occasions) or low (LDS, sodium excretion <100 mmol/24 h on two out of three consecutive occasions) salt intake. METHODS: Patients received 4 weeks of telmisartan followed by 4 weeks of telmisartan plus hydrochlorothiazide. In a double-blind randomised fashion, patients received sodium chloride (NaCl, 100 mmol/24 h) or placebo capsules in addition to their habitual salt intake during the last 2 weeks of telmisartan and telmisartan plus hydrochlorothiazide therapy. The protocol was repeated with NaCl and placebo capsules administered in reverse order to allow each participant to act as his or her own control. At 0, 4, 8, 14, 18 and 22 weeks, 24 h ambulatory blood pressure (ABP) and 24 h urine collections were performed. RESULTS: No statistically significant differences were seen in the ABP response in the LDS vs HDS groups to any of the interventions (p = 0.58). NaCl supplementation reduced the effect of telmisartan with or without hydrochlorothiazide on systolic BP by approximately 50% (-5.8 mmHg during NaCl supplementation vs -11.3 mmHg during placebo, mean difference 5.6 mmHg [95% CI 1.7-9.4 mmHg], p = 0.005), irrespective of habitual salt intake. By contrast, addition of hydrochlorothiazide increased the antihypertensive effect of telmisartan on systolic BP by approximately 35% (p = 0.048) in both groups of patients. CONCLUSIONS/INTERPRETATION: NaCl supplementation blunts the effectiveness of telmisartan with or without hydrochlorothiazide in hypertensive patients with type 2 diabetes, independently of habitual low or high salt intake.

High sodium and low potassium intake in patients with Type 2 diabetes.

AIMS: To document dietary sodium and potassium intake and adherence to the Australian National Heart Foundation (NHF) guidelines in patients with Type 2 diabetes mellitus attending an Australian tertiary referral and university teaching hospital. METHODS: In a longitudinal study, 24h urinary sodium (uNa), potassium (uK), creatinine (uCr), urea (uUrea) and glucose (uGlu) excretions, urine volume (uVol) and body mass index were recorded in 122 regular attenders over an 8 year period (2001-2008; mean of 1.9 samples/patient/year). In a cross-sectional study, the same measurements were recorded in patients providing urine samples in the month of June from 2001 to 2009 (782 patients, averaging 87/year). RESULTS: In the longitudinal study, uNa (mmol/24 h) was 170 ± 53 (mean ± SD) in males and 142 ± 51 in females, whereas uK (mmol/24 h) was 75 ± 22 in males and 62 ± 18 in females. Once adjusted for insensible losses, only 3% of males and 14% of females met the NHF dietary sodium intake guidelines, and 14% of males and 3% of female patients met the NHF dietary potassium guidelines. Body mass index, uUrea, uVol and uGlu were independent predictors of uNa (adjusted r(2) =0.57, P<0.0001). The mean intra-individual coefficient of variation of the corrected uNa was 21 ± 1%. The cross-sectional study confirmed these findings, and no temporal trends were observed. There was no correlation with glycated haemoglobin to suggest natriuresis with hyperglycaemia. CONCLUSIONS: Most patients with Type 2 diabetes mellitus do not meet NHF sodium or potassium intake guidelines. A diet high in sodium and low in potassium may contribute to the development of hypertension and to resistance to blood-pressure-lowering therapies.

Change in emotional eating after bariatric surgery: systematic review and meta-analysis.

BACKGROUND: The effect of bariatric surgery on 'emotional eating' (EE) in people with obesity is unclear. This systematic review and meta-analysis aimed to examine changes in self-reported emotional eating behaviour after bariatric surgery. METHODS: Fifteen electronic databases were searched from inception to August 2019. Included studies encompassed patients undergoing primary bariatric surgery, quantitatively assessed EE, and reported EE scores before and after surgery in the same participants. Studies were excluded if they were not in English or available in full text. The systematic review and meta-analysis were conducted according to the PRISMA guidelines. Random-effects models were used for quantitative analysis. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tool for before-after (pre-post) studies with no control group. RESULTS: Some 23 studies containing 6749 participants were included in the qualitative synthesis, with follow-up of from 2 weeks to 48 months. EE scores decreased to 12 months after surgery. Results were mixed beyond 12 months. Quantitative synthesis of 17 studies (2811 participants) found that EE scores decreased by a standardized mean difference of 1·09 (95 per cent c.i. 0·76 to 1·42) 4-18 months after surgery, indicating a large effect size. CONCLUSION: Bariatric surgery may mitigate the tendency to eat in response to emotions in the short to medium term.

ANTECEDENTES: El efecto de la cirugía bariátrica sobre la "alimentación emocional" (emotional eating, EE) en personas con obesidad no esta claro. Esta revisión sistemática y metaanálisis tuvo como objetivo examinar los cambios en el comportamiento de la alimentación emocional referida por los mismos pacientes después de cirugía bariátrica. MÉTODOS: Se realizó una búsqueda en 15 bases de datos electrónicas desde el inicio de las mismas hasta agosto de 2019. Los estudios seleccionados incluían pacientes con cirugía bariátrica primaria, EE evaluada de forma cuantitativa, y descripción de las puntuaciones de EE antes y después de la cirugía en los mismos participantes. Se excluyeron estudios que no estuvieran publicados en inglés o si no se disponía del texto completo. Esta revisión sistemática y metaanálisis se llevó a cabo de acuerdo con las recomendaciones PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Se utilizó un modelo de efectos aleatorios para el análisis cuantitativo. La calidad de los estudios individuales se evaluó utilizando la herramienta de evaluación de la calidad NHLBI para estudios de antes-después (pre-post) sin grupo control. RESULTADOS: Se incluyeron un total de 23 estudios con 6.749 participantes en la síntesis cualitativa, y un seguimiento de 2 semanas a 48 meses. Las puntuaciones EE disminuyeron a los 12 meses postoperatorios. Los resultados fueron variados más allá de los 12 meses. La síntesis cuantitativa de 17 estudios (2.811 participantes) encontró que las puntuaciones EE disminuyeron con una diferencia de medias ponderada de 1,09 (i.c. del 95% 0,76, 1,42) a los 4-18 meses tras la operación, lo que indica una magnitud de efecto grande. CONCLUSIÓN: La cirugía bariátrica puede atenuar la tendencia a comer en respuesta a las emociones en el corto y medio plazo.

Diabetes and higher HbA1c levels are independently associated with adverse renal outcomes in inpatients following multiple hospital admissions.

OBJECTIVE: To assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions. DESIGN: A prospective observational cohort study. PARTICIPANTS: All inpatients aged ≥54 years admitted between 2013 and 16 to a tertiary hospital. MAIN OUTCOMES: We prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30 ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5 mL/min/1·73m2/year) and (c) final eGFR<30 ml/min/1·73m2. RESULTS: Of 4126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR = 1·42;95% CI:1·18-1·70;p < 0·001); (b) rapid decline in renal function (OR = 1·40;95%CI:1·20-1·63;p < 0·001), and (c) reaching eGFR<30 ml/min/1.73m2 (OR = 1·25;95%CI:1·03-1·53;p < 0·05). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR = 1·07;95% CI:1·01-1·4;p < 0·05) and (b) rapid decline in renal function (OR = 1·11;95% CI:1·05-1·18;p < 0·001). CONCLUSIONS: In patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

Routine use of HbA1c amongst inpatients hospitalised with decompensated heart failure and the association of dysglycaemia with outcomes.

Diabetes is an independent risk factor for development of heart failure and has been associated with poor outcomes in these patients. The prevalence of diabetes continues to rise. Using routine HbA1c measurements on inpatients at a tertiary hospital, we aimed to investigate the prevalence of diabetes amongst patients hospitalised with decompensated heart failure and the association of dysglycaemia with hospital outcomes and mortality. 1191 heart failure admissions were identified and of these, 49% had diabetes (HbA1c ≥ 6.5%) and 34% had pre-diabetes (HbA1c 5.7-6.4%). Using a multivariable analysis adjusting for age, Charlson comorbidity score (excluding diabetes and age) and estimated glomerular filtration rate, diabetes was not associated with length of stay (LOS), Intensive Care Unit (ICU) admission or 28-day readmission. However, diabetes was associated with a lower risk of 6-month mortality. This finding was also supported using HbA1c as a continuous variable. The diabetes group were more likely to have diastolic dysfunction and to be on evidence-based cardiac medications. These observational data are hypothesis generating and possible explanations include that more diabetic patients were on medications that have proven mortality benefit or prevent cardiac remodelling, such as renin-angiotensin system antagonists, which may modulate the severity of heart failure and its consequences.

The impact of hyperfiltration on the diabetic kidney.

More than two decades ago, hyperfiltration (HF) in diabetes was postulated to be a maladaptive response observed early in the course of diabetic kidney disease (DKD), which may eventually predispose to irreversible damage to nephrons and development of progressive renal disease. Despite this, the potential mechanisms leading to renal HF in diabetes are not fully understood, although several hypotheses have been proposed, including alterations in glomerular haemodynamic function and tubulo-glomerular feedback. Furthermore, the role of HF as a causative factor in renal disease progression is still unclear and warrants further prospective longer-term studies. Although HF has been entrenched as the first stage in the classic albuminuric pathway to end-stage renal disease in DKD, and HF has been shown to predict the progression of albuminuria in many, but not all studies, the concept that HF predisposes to the development of chronic kidney disease (CKD) stage 3, that is, glomerular filtration rate (GFR) decline to<60mL/min/1.73m(2), remains to be proved. Further long-term studies of GFR gradients therefore are required to establish whether HF ultimately leads to decreased kidney function, after adjustment for glycaemic control and other confounders. Whether reversal of HF with therapeutic agents is protective against reducing the risk of development of albuminuria and renal impairment is also worth investigating in prospective randomized trials.

Neurological manifestations of cardiac myxoma: a review of the literature and report of cases.

BACKGROUND AND AIMS: Cardiac myxoma is a rare but important cause of stroke, which affects young people. More recently the diagnosis has been enhanced by the use of echocardiograms. We aimed to review the neurological presentations, including stroke, of cardiac myxoma in this modern era of diagnosis and management. METHODS: Records of patients with neurological presentations at the Austin and Repatriation Medical Centre and The Northern Hospital were retrieved from 1985 to late 2001, using International Classification of Diseases codes for atrial myxoma. Published literature reports were obtained by using Medline search database. An iterative process of bibliography review was utilised to identify reports not found by primary search. Case demographics, neurological presentations, investigations, treatment and outcome were recorded. RESULTS: From the Austin and Repatriation Medical Centre and The Northern Hospital, 6 cases were reported in detail and 107 cases from the published literature were analysed. The mean age of all cases was 43 (range 6-82). There was a female to male predominance (3:2). While there were overlapping neurological presentations, the most common presentation was ischaemic stroke (83% of all patients) most often in multiple sites (41%). The other presentations included syncope (28%), psychiatric presentations (23%), headache (15%) and seizures (12%). Commonest means of reaching the diagnosis was by echocardiography. The myxoma was surgically resected in 69% of cases. Of all cases, 24% were autopsy reports, almost all prior to availability of echocardiograms (in mid-1970s). CONCLUSIONS: Patients who presented with neurological complications of cardiac myxoma were young and stroke was by far the most common single presentation. Importantly, when all clinical manifestations were considered, almost half were potentially reversible. In recent years, echocardiography has made significant contribution to establishing the diagnosis less invasively. There is uncertainty about the role of anticoagulants. The treatment of choice remains surgical excision, although the timing post stroke is debatable. There is a need for large scale collaborative studies to help refine management strategies.