PATIENT CONCERNS: A 61-year-old Asian female with underlying type 2 DM presented to our ED with body weakness, dyspnea, nausea, vomiting, and mild abdominal pain for the past 2 days. These symptoms were preceded by poor oral intake for 1 week due to severe toothache. Dapagliflozin was recently added to her antidiabetic drug regimen of metformin and glibenclamide 2 weeks ago.
DIAGNOSES: Arterial blood gases showed a picture of severe metabolic acidosis with an elevated anion gap, while ketones were elevated in blood and positive in urine. Blood glucose was mildly elevated at 180 mg/dL. Serum lactate levels were normal. Our patient was thus diagnosed with eDKA.
INTERVENTION: Our patient was promptly admitted to the intensive care unit and treated for eDKA through intravenous rehydration therapy with insulin infusion.
OUTCOMES: Serial blood gas analyses showed gradual resolution of the patient's ketoacidosis with normalized anion gap and clearance of serum ketones. She was discharged uneventfully on day 4, with permanent cessation of dapagliflozin administration.
LESSONS: Life-threatening eDKA as a complication of dapagliflozin is a challenging and easilymissed diagnosis in the ED. Such an ED presentation is very rare, nevertheless emergency physicians are reminded to consider the diagnosis of eDKA in a patient whose drug regimen includes any SGLT2 inhibitor, especially if the patient presents with nausea, vomiting, abdominal pain, dyspnea, lethargy, and is clinically dehydrated. These patients should then be investigated with ketone studies and blood gas analyses regardless of blood glucose levels for prompt diagnosis and treatment.
OBJECTIVES: To assess the efficacy and safety of combined aclidinium bromide and long-acting beta2-agonists in stable COPD.
SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, World Health Organization (WHO) trials portal, United States Food and Drug Administration (FDA) and manufacturers' websites as well as the reference list of published trials up to 12 October 2018.
SELECTION CRITERIA: Parallel-group randomised controlled trials (RCTs) assessing combined aclidinium bromide and LABAs in people with stable COPD.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane for data collection and analysis. The primary outcomes were exacerbations requiring a short course of an oral steroid or antibiotic, or both; quality of life measured by a validated scale and non-fatal serious adverse events (SAEs). Where the outcome or study details were not reported, we contacted the study investigators or pharmaceutical company trial co-ordinators (or both) for missing data.
MAIN RESULTS: We identified RCTs comparing aclidinium/formoterol FDC versus aclidinium, formoterol or placebo only. We included seven multicentre trials of four to 52 weeks' duration conducted in outpatient settings. There were 5921 participants, whose mean age ranged from 60.7 to 64.7 years, mostly men with a mean smoking pack-years of 46.4 to 61.3 of which 43.9% to 63.4% were current smokers. They had a moderate-to-severe degree of COPD with a mean postbronchodilator forced expiratory volume in one second (FEV1) between 50.5% and 61% of predicted normal and the baseline mean FEV1 of 1.23 L to 1.43 L. We assessed performance and detection biases as low for all studies whereas selection, attrition and reporting biases were either low or unclear.FDC versus aclidiniumThere was no evidence of a difference between FDC and aclidinium for exacerbations requiring steroids or antibiotics, or both (OR 0.95, 95% CI 0.71 to 1.27; 2 trials, 2156 participants; moderate-certainty evidence); quality of life measured by St George's Respiratory Questionnaire (SGRQ) total score (MD -0.92, 95% CI -2.15 to 0.30); participants with significant improvement in SGRQ score (OR 1.17, 95% CI 0.97 to 1.41; 2 trials, 2002 participants; moderate-certainty evidence); non-fatal SAE (OR 1.19, 95% CI 0.79 to 1.80; 3 trials, 2473 participants; moderate-certainty evidence); hospital admissions due to severe exacerbations (OR 0.62, 95% CI 0.29 to 1.29; 2 trials, 2156 participants; moderate-certainty evidence) or adverse events (OR 0.95, 95% CI 0.76 to 1.18; 3 trials, 2473 participants; moderate-certainty evidence). Compared with aclidinium, FDC improved symptoms (Transitional Dyspnoea Index (TDI) focal score: MD 0.37, 95% CI 0.07 to 0.68; 2 trials, 2013 participants) with a higher chance of achieving a minimal clinically important difference (MCID) of at least one unit improvement (OR 1.34, 95% CI 1.11 to 1.62; high-certainty evidence); the number needed to treat for an additional beneficial outcome (NNTB) being 14 (95% CI 9 to 39).FDC versus formoterolWhen compared to formoterol, combination therapy reduced exacerbations requiring steroids or antibiotics, or both (OR 0.78, 95% CI 0.62 to 0.99; 3 trials, 2694 participants; high-certainty evidence); may decrease SGRQ total score (MD -1.88, 95% CI -3.10 to -0.65; 2 trials, 2002 participants; low-certainty evidence; MCID for SGRQ is 4 units); increased TDI focal score (MD 0.42, 95% CI 0.11 to 0.72; 2 trials, 2010 participants) with more participants attaining an MCID (OR 1.30, 95% CI 1.07 to 1.56; high-certainty evidence) and an NNTB of 16 (95% CI 10 to 60). FDC lowered the risk of adverse events compared to formoterol (OR 0.78, 95% CI 0.65 to 0.93; 5 trials, 3140 participants; high-certainty evidence; NNTB 22). However, there was no difference between FDC and formoterol for hospital admissions, all-cause mortality and non-fatal SAEs.FDC versus placeboCompared with placebo, FDC demonstrated no evidence of a difference in exacerbations requiring steroids or antibiotics, or both (OR 0.82, 95% CI 0.60 to 1.12; 2 trials, 1960 participants; moderate-certainty evidence) or hospital admissions due to severe exacerbations (OR 0.55, 95% CI 0.25 to 1.18; 2 trials, 1960 participants; moderate-certainty evidence), although estimates were uncertain. Quality of life measure by SGRQ total score was significantly better with FDC compared to placebo (MD -2.91, 95% CI -4.33 to -1.50; 2 trials, 1823 participants) resulting in a corresponding increase in SGRQ responders who achieved at least four units decrease in SGRQ total score (OR 1.72, 95% CI 1.39 to 2.13; high-certainty evidence) with an NNTB of 7 (95% CI 5 to 12). FDC also improved symptoms measured by TDI focal score (MD 1.32, 95% CI 0.96 to 1.69; 2 studies, 1832 participants) with more participants attaining at least one unit improvement in TDI focal score (OR 2.51, 95% CI 2.02 to 3.11; high-certainty evidence; NNTB 4). There were no differences in non-fatal SAEs, adverse events and all-cause mortality between FDC and placebo.Combination therapy significantly improved trough FEV1 compared to aclidinium, formoterol or placebo.
AUTHORS' CONCLUSIONS: FDC improved dyspnoea and lung function compared to aclidinium, formoterol or placebo, and this translated into an increase in the number of responders on combination treatment. Quality of life was better with combination compared to formoterol or placebo. There was no evidence of a difference between FDC and monotherapy or placebo for exacerbations, hospital admissions, mortality, non-fatal SAEs or adverse events. Studies reported a lower risk of moderate exacerbations and adverse events with FDC compared to formoterol; however, larger studies would yield a more precise estimate for these outcomes.
DESIGN: Planned substudy of the prospective, descriptive cohort study: Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM).
SETTING: 46 EDs in Australia, New Zealand, Singapore, Hong Kong and Malaysia collected data over 3 72-hour periods in May, August and October 2014.
PARTICIPANTS: Patients with an ED diagnosis of heart failure.
OUTCOME MEASURES: Outcomes included patient epidemiology, investigations ordered, treatment modalities used and patient outcomes (hospital length of stay (LOS) and mortality).
RESULTS: 455 (14.9%) of the 3044 patients had an ED diagnosis of heart failure. Median age was 79 years, half were male and 62% arrived via ambulance. 392 (86%) patients were admitted to hospital. ED diagnosis was concordant with hospital discharge diagnosis in 81% of cases. Median hospital LOS was 6 days (IQR 4-9) and in-hospital mortality was 5.1%. Natriuretic peptide levels were ordered in 19%, with lung ultrasound (<1%) and echocardiography (2%) uncommonly performed. Treatment modalities included non-invasive ventilation (12%), diuretics (73%), nitrates (25%), antibiotics (16%), inhaled β-agonists (13%) and corticosteroids (6%).
CONCLUSIONS: In the Asia Pacific region, heart failure is a common diagnosis among patients presenting to the ED with a principal symptom of dyspnoea. Admission rates were high and ED diagnostic accuracy was good. Despite the seemingly suboptimal adherence to investigation and treatment guidelines, patient outcomes were favourable compared with other registries.
Learning points: Thyrotoxicosis is associated with right ventricular dysfunction and pulmonary hypertension apart from left ventricular dysfunction described in typical thyrotoxic cardiomyopathy.Symptoms and signs of right ventricular dysfunction and pulmonary hypertension should be sought in all patients with newly diagnosed thyrotoxicosis.Thyrotoxicosis should be considered in all cases of right ventricular dysfunction or pulmonary hypertension not readily explained by other causes.Prompt restoration of euthyroidism is warranted in patients with thyrotoxicosis complicated by right ventricular dysfunction with or without pulmonary hypertension to allow timely resolution of the abnormal cardiac parameters before development of overt right heart failure.
Learning points: Cushing's syndrome can present in many ways, a high index of suspicion is required for its diagnosis, as often patients present with only few of the pathognomonic symptoms and signs of the syndrome.Proximal lower-limb girdle myopathy is common in Cushing's syndrome. Less often long-term exposure of excess glucocorticoid production can also affect other muscles including respiratory muscle and the diaphragm leading to progressive shortness of breath and even acute respiratory failure.Treatment of Cushing's myopathy involves treating the underlying cause that is hypercortisolism. Various medications have been suggested to hinder the development of GC-induced myopathy, but their effects are poorly analysed.
CASE PRESENTATION: However, here we report a case of DNPE with a slightly different presentation where there is no preceding trauma and has symptoms that mimic severe pneumonia. He presented with high fever, dyspnoea and pleuritic chest pain. Despite on 10 L of oxygen supplementation via high flow mask and already given bolus intravenous antibiotic, the patient still tachypnoeic and was persistently in type I respiratory failure. His chest X-ray showed consolidative changes. Upon further investigation revealed no evidence of DVT on Doppler ultrasound and normal D-dimer level. Due to the high index of suspicion by the attending physician, PE was suspected and later confirmed with computed tomography pulmonary angiography scan. He was successfully treated with anticoagulation therapy. The objective of this case report is to share the difficult experience of diagnosing PE when the presentation highly atypical and mimics severe pneumonia.
CONCLUSION: And with such a masquerading presentation, one can easily miss the diagnosis. To the best of our knowledge, there are very few similar cases reported.