Acetazolamide for metabolic alkalosis complicating respiratory failure with chronic obstructive pulmonary disease or obesity hypoventilation syndrome: a systematic review.

BACKGROUND: Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic respiratory disease. Acetazolamide can reduce alkalaemia and may reduce respiratory depression. METHODS: We searched Medline, EMBASE and CENTRAL from inception to March 2022 for randomised controlled trials comparing acetazolamide to placebo in patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or obstructive sleep apnoea, hospitalised with acute respiratory deterioration complicated by metabolic alkalosis. The primary outcome was mortality and we pooled data using random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 (Risk of Bias 2) tool, heterogeneity was assessed using the I2 value and χ2 test for heterogeneity. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology. RESULTS: Four studies with 504 patients were included. 99% of included patients had chronic obstructive pulmonary disease. No trials recruited patients with obstructive sleep apnoea. 50% of trials recruited patients requiring mechanical ventilation. Risk of bias was overall low to some risk. There was no statistically significant difference with acetazolamide in mortality (relative risk 0.98 (95% CI 0.28 to 3.46); p=0.95; 490 participants; three studies; GRADE low certainty) or duration of ventilatory support (mean difference -0.8 days (95% CI -7.2 to 5.6); p=0.36; 427 participants; two studies; GRADE: low certainty). CONCLUSION: Acetazolamide may have little impact on respiratory failure with metabolic alkalosis in patients with chronic respiratory diseases. However, clinically significant benefits or harms are unable to be excluded, and larger trials are required. PROSPERO REGISTRATION NUMBER: CRD42021278757.

The extent of polypharmacy and use of 'fall risk increasing drugs' in the oldest old admitted to a regional New South Wales hospital.

OBJECTIVE(S): Polypharmacy is associated with significant morbidity including cognitive decline and falls. We sought to quantify the extent of polypharmacy and use of medications associated with fall risk in the very old admitted to a regional NSW hospital. METHODS: Cross-sectional study of patients aged over 80 years admitted to a regional NSW hospital from September to October 2019. Demographic data and medication usage on admission were collected. Polypharmacy was defined as regular use of five or more medications. RESULTS: A total of 401 patients were included: mean age was 87.2 (±4.6) years and 56.9% were female. Of the participations, 82.9% experienced polypharmacy, and the mean number of medications was 8.2 (±4.2). Of the patients, 91.6% utilised medications associated with risk of falls. There was no association between age and number of preadmission regular medications. CONCLUSION: Polypharmacy is extremely common prior to acute hospitalisation for regional older individuals. This highlights the importance of medication rationalisation to reduce medication-related harm.

Using Coronary Artery Calcium Scoring as Preventative Health Tool to Reduce the High Burden of Cardiovascular Disease in Indigenous Australians.

BACKGROUND: Indigenous Australians suffer higher rates of ischaemic heart disease resulting in premature mortality. Despite this, Indigenous Australians undergo less cardiovascular investigation and intervention than their non-Indigenous counterparts. Recent evidence suggests that computed tomography coronary angiography (CTCA) is not only able to accurately predict cardiovascular risk, but also results in reduced rates of myocardial infarction and cardiovascular death. METHODS: This is a prospective longitudinal study of patients in regional Australia referred for CTCA at a regional centre from 2012 to 2017. Patients were identified as Indigenous at registration. Results were recorded from formal radiology reports. Logistic regression was used to compare calcium score, as a measure of coronary artery disease burden in Indigenous and non-Indigenous patients. RESULTS: Indigenous patients are 2.8 times more likely to have a higher burden of coronary artery disease than non-Indigenous patients, even after accounting for the higher rate of cardiovascular risk factors in the Indigenous population (OR 2.77; p = 0.008). In the study population, Indigenous patients were well represented as compared to the background population. CONCLUSION: This is the first study of CTCA in an Indigenous Australian population, and one of the first using CTCA for an Indigenous population worldwide. It demonstrates a higher burden of cardiovascular disease for Indigenous Australians, independent of the higher rate of cardiovascular risk factors. Access to CTCA presents an opportunity to reduce the rate of myocardial infarction and early mortality in the Indigenous Australian population.

A-Band Titin Truncation in Zebrafish Causes Dilated Cardiomyopathy and Hemodynamic Stress Intolerance.

Background Truncating variants in the TTN gene ( TTNtv) are common in patients with dilated cardiomyopathy (DCM) but also occur in the general population. Whether TTNtv are sufficient to cause DCM or require a second hit for DCM manifestation is an important clinical issue. Methods We generated a zebrafish model of an A-band TTNtv identified in 2 human DCM families in which early-onset disease appeared to be precipitated by ventricular volume overload. Cardiac phenotypes were serially assessed from 0 to 12 months using video microscopy, high-frequency echocardiography, and histopathologic analysis. The effects of sustained hemodynamic stress resulting from an anemia-induced hyperdynamic state were also evaluated. Results Homozygous ttna mutants had severe cardiac dysmorphogenesis and premature death, whereas heterozygous mutants ( ttnatv/+) survived into adulthood and spontaneously developed DCM. Six-month-old ttnatv/+ fish had reduced baseline ventricular systolic function and failed to mount a hypercontractile response when challenged by hemodynamic stress. Pulsed wave and tissue Doppler analysis also revealed unsuspected ventricular diastolic dysfunction in ttnatv/+ fish with prolonged isovolumic relaxation and increased diastolic passive stiffness in the absence of myocardial fibrosis. These defects reduced diastolic reserve under stress conditions and resulted in disproportionately greater atrial dilation than observed in wild-type fish. Conclusions Heterozygosity for A-band titin truncation is sufficient to cause DCM in adult zebrafish. Abnormalities of systolic and diastolic reserve in titin-truncated fish reduce stress tolerance and may contribute to a substrate for atrial arrhythmogenesis. These data suggest that hemodynamic stress may be an important modifiable risk factor in human TTNtv-related DCM.