Hypocalcaemia following denosumab in prostate cancer: A clinical review.

OBJECTIVES: Denosumab is often used in men with advanced prostate cancer to prevent skeletal-related events, but can be associated with severe hypocalcaemia. Our objective was to review the pathophysiology, identify risk factors and provide recommendations for prevention and management of denosumab-associated hypocalcaemia. DESIGN: We reviewed the literature regarding denosumab-associated severe hypocalcaemia, defined as necessitating hospitalization for intravenous calcium treatment, in the context of prostate cancer. PATIENTS: Men with prostate cancer with severe denosumab-associated hypocalcemia. RESULTS: We identified 20 men with prostate cancer with severe denosumab-associated hypocalcemia, including the present case. Median age (range) was 70 years (45-86). All had skeletal metastases and presented with symptomatic hypocalcemia 16 days (4-35) after the initial (n = 18) or second (n = 2) denosumab treatment, with a serum total calcium of 1.36 mmol/L (1.13-1.91). The key risk factor was presence of active osteoblastic metastases, evidenced by elevated serum alkaline phosphatase, 838 U/L (58-2620) and supportive imaging. Other risk factors reported in some men included vitamin D deficiency (<50 nmol/L), 25-OH vitamin D 44 nmol/L (22-81), renal impairment, serum creatinine 103 µmol/L (62-1131) and hypomagnesaemia, 0.82 mmol/L (0.29-1.20). Men received intravenous calcium infusions for 16 days (1-90), and median total intravenous elemental calcium requirements were 3.17 g (0.47-26.65). CONCLUSIONS: Denosumab treatment in men with metastatic prostate cancer can be associated with life-threatening hypocalcaemia requiring prolonged hospitalization for intravenous calcium treatment. Modifiable risk factors should be corrected before denosumab administration. In men with active osteoblastic metastases, consideration should be given to delay denosumab treatment until underlying disease activity is controlled, and/or be administered with close monitoring and proactive treatment with calcium and calcitriol.

Feasibility trial of metformin XR in people with pre-diabetes and stroke (MIPPS)-randomised open blinded endpoint controlled trial.

AIMS: Pre-diabetes is a common condition that affects about 16.4% of Australian adults. Hyperglycaemia is a strong risk factor for the development of stroke. Metformin XR is an approved medication to treat type 2 diabetes in Australia but not pre-diabetes. Additionally, whether it is tolerated following a stroke is unclear. In this pilot study, we aimed to assess the feasibility of Metformin XR in people with stroke and pre-diabetes. METHODS: In this PROBE design trial, people who had recent stroke (within 3 months) with pre-diabetes were randomized to either the active arm (n = 13) receiving usual care plus Metformin XR (500 mg daily increased to a total daily dose of 1500 mg) or the control group receiving only usual care (n = 13). At baseline & after four months of intervention, clinical and biomedical characteristics, cardiovascular risk factors and medication data were recorded. At one month and 2.5 months into the study, compliance rateandside effects were determined. RESULTS: This trial showed that it is feasible to recruit, retain and monitor participants. However, the compliance rate was low. Adherence to metformin XR was 52% (IQR:42% to 61%) based on the remaining tablets in the container after 4 months of intervention. None of the reported side effects were deemed to be related to the study treatment and no significant differences were observed between the metformin XR and the control group. CONCLUSION: Treatment with Metformin XR in participants admitted with stroke and with pre-diabetes is feasible and safe. Strategies are needed to improve adherence in future trials.

Prevalence of diabetes and its effects on stroke outcomes: A meta-analysis and literature review.

AIMS/INTRODUCTION: Diabetes mellitus is an established risk factor for stroke and maybe associated with poorer outcomes after stroke. The aims of the present literature review were to determine: (i) the prevalence of diabetes in acute stroke patients through a meta-analysis; (ii) the association between diabetes and outcomes after ischemic and hemorrhagic stroke; and (iii) to review the value of glycated hemoglobin and admission glucose-based tests in predicting stroke outcomes. MATERIALS AND METHODS: Ovid MEDLINE and EMBASE searches were carried out to find studies relating to diabetes and inpatient stroke populations published between January 2004 and April 2017. A meta-analysis of the prevalence of diabetes from included studies was undertaken. A narrative review on the associations of diabetes and different diagnostic methods on stroke outcomes was carried out. RESULTS: A total of 66 eligible articles met inclusion criteria. A meta-analysis of 39 studies (n = 359,783) estimated the prevalence of diabetes to be 28% (95% confidence interval 26-31). The rate was higher in ischemic (33%, 95% confidence interval 28-38) compared with hemorrhagic stroke (26%, 95% confidence interval 19-33) inpatients. Most, but not all, studies found that acute hyperglycemia and diabetes were associated with poorer outcomes after ischemic or hemorrhagic strokes: including higher mortality, poorer neurological and functional outcomes, longer hospital stay, higher readmission rates, and stroke recurrence. Diagnostic methods for establishing diagnosis were heterogeneous between the reviewed studies. CONCLUSIONS: Approximately one-third of all stroke patients have diabetes. Uniform methods to screen for diabetes after stroke are required to identify individuals with diabetes to design interventions aimed at reducing poor outcomes in this high-risk population.

Routine HbA1c among hematology and oncology inpatients: Diabetes-status and hospital-outcomes.

AIMS: Using routine HbA1c measurement to determine the prevalence of diabetes mellitus (known and previously unrecognized) and their hospital outcomes among hematology and oncology inpatients. METHODS: This was a prospective, observational study. Routine automated HbA1c testing was performed in all hematology and oncology inpatients aged ≥54 years at a tertiary hospital, July 2013-January 2015. The outcome measures were: (i) prevalence of known and previously unrecognized diabetes, and (ii) hospital outcomes: length-of-stay (LOS), intensive-care-unit (ICU) admission, 30-day/18-month readmission, and 18-month mortality. RESULTS: Over the 18-month study period, 1076 inpatients aged ≥54 years were admitted to hematology (n = 298) and oncology (n = 778) units: 21% had known diabetes and 7% had previously unrecognized diabetes. Patients with known diabetes had a longer LOS (IRR: 1.18, 95%CI: 1.02-1.37, p = 0.03), compared to those without diabetes, adjusting for age, hemoglobin level, estimated-glomerular-filtration-rate, admission specialty unit, Charlson's comorbidity index score, and glucocorticoid exposure. No significant differences were observed in ICU admission, 30-day/18-month readmission, and 18-month mortality among patients with known, previously unrecognized and no diabetes (p ≥ 0.05). CONCLUSIONS: Approximately one in five hematology or oncology inpatients aged ≥54 years had known diabetes, and one in fourteen had previously unrecognized diabetes. Those with known diabetes had a longer hospital stay. Routine HbA1c measurement is can be useful for identifying previously unrecognized diabetes, particularly among patients with high glucocorticoid exposure. Further study is required to determine cost-effectiveness in screening for unrecognized diabetes and optimal management of these patients.

Using routine HbA1c measurements in stroke and the associations of dysglycaemia with stroke outcomes.

AIMS: Diabetes is a major risk factor for stroke. We aimed to investigate the prevalence of diabetes and pre-diabetes within a stroke cohort and examine the association of glycaemia status with mortality and morbidity. METHODS: Inpatients aged ≥54 who presented with a diagnosis of stroke had a routine HbA1c measurement as part of the Austin Health Diabetes Discovery Initiative. Additional data were attained from hospital databases and Australian Stroke Clinical Registry. Outcomes included diabetes and pre-diabetes prevalence, length of stay, 6-month and in-hospital mortality, 28-day readmission rates, and 3-month modified Rankin scale score. RESULTS: Between July 2013 and December 2015, 610 patients were studied. Of these, 31% had diabetes while 40% had pre-diabetes. Using multivariable regression analyses, the presence of diabetes was associated with higher odds of 6-month mortality (OR = 1.90, p = 0.022) and higher expected length of stay (IRR = 1.29, p = 0.004). Similarly, a higher HbA1c was associated with higher odds of 6-month mortality (OR = 1.27, p = 0.005) and higher expected length of stay (IRR = 1.08, p = 0.010). CONCLUSIONS: 71% of this cohort had diabetes or pre-diabetes. Presence of diabetes and higher HbA1c were associated with higher 6-month mortality and length of stay. Further research is necessary to determine if improved glycaemic control may improve stroke outcomes.

Nurse practitioners treating ankle and foot injuries using the Ottawa Ankle Rules: a comparative study in the emergency department.

BACKGROUND: Nurse practitioners (NPs) in the Emergency Department (ED) have been trained to assess a range of clinical problems and minor complaints such as acute ankle injury. This study compared assessment of suspected ankle and foot injuries using the Ottawa Ankle Rules (OAR) by NPs and ED medical doctors (ED-Drs). METHODS: A prospective, comparative, observational study was undertaken in an Australian acute adult and paediatric urban district ED. NPs and ED-Drs recorded information for patients with acute ankle and/or mid-foot injuries on demographic characteristics, OAR features, use of X-ray and patient management. Outcome measures included X-ray rates and identification of fracture. RESULTS: 174 patients were included in this study: 51 received NP and 123 received ED-Dr care. Assessed as requiring X-ray assessment (NP: 78.4%, ED-Dr: 88.6%; p=0.081), and detection of significant fracture (NP: 17.6%, ED-Dr: 22.8%; p=0.453) were similar. ED-based medical registrars were more likely to miss a fracture compared with NP (NP: 0%, ED-based Registrar: 28.6%, p=0.013). There were no significant differences in rates of OAR features for patients seen by NPs or ED-Drs. CONCLUSION: This study suggests that NPs are less likely to miss significant fractures of the ankle and/or foot compared with ED-based medical registrars. Future research should focus on actual use of the OAR and accuracy of X-ray assessment by NPs.