Round Up Email September 2022

This month's Round Up includes updates with respect to the DELIVER study - the use of dapagliflozin in heart failure with mildly reduced ejection fraction (HFmrHEF) and heart failure with preserved ejection fraction (HFpEF); an update regarding nitrous oxide misuse; and evidence relating to the number of steps per day required to reduce risk of cancer and dementia.

Question 1
Nitrous oxide misuse – what are the complications associated with nitrous oxide misuse? How prevalent is nitrous oxide misuse in 16-24 year olds? What is the mechanism for pathology associated with nitrous oxide misuse?: Nitrous oxide misuse
1) With respect to nitrous oxide misuse, which statement is false?
- 2019-20 Crime Survey for England and Wales found that almost 9% of 16-24 year olds said that they had taken nitrous oxide in the previous year, up from 6.1% in 2012-13
- toxic effects are mediated by inactivation of folic acid, typically producing a myelopathy
- in most cases reported in the literature, the neurological presentation associated with nitrous oxide misuse is that of a myelopathy particularly affecting the dorsal columns-subacute combined degeneration of the spinal cord
Question 2
Step count and cancer risk – a population study has investigated the reduction in risk of developing cancer in relation to the number of steps per day an individual undertakes. The study used data from the UK Biobank for 2013 to 2015 (median follow-up, 7 years) and included adults 40 to 79 years old in England, Scotland, and Wales. Participants had a wrist accelerometer which measured daily step count and established cadence-based step intensity measures (steps/min). Is there an optimum number of steps per day to reduce cancer risk?: Steps per day and cancer risk
2) With respect to step count and cancer risk, which statement is false?
- findings indicate that accumulating more steps per day (up to about 10,000) may be associated with a lower risk of cancer, and CVD mortality
- peak-30 cadence (stepping intensity) showed consistent associations with improved morbidity and mortality rates
- findings indicate that accumulating more steps per day (up to about 5,000) may be associated with a lower risk of all-cause mortality
Question 3
Step count and dementia risk - This study involving the same study population as the Step count and cancer risk study , investigated the reduction in risk of developing dementia based on number of steps per day. Is there an optimum number of steps per day to reduce dementia risk?: Exercise and dementia risk
3) With respect to step count and dementia risk, which statement is false?
- a higher number of steps was linked to lower risk of all-cause dementia
- the optimal dose was estimated at 6800 steps per day to prevent dementia
- intensity of steps, more than the mere volume of steps, is a potent purveyor of the clinical benefits of stepping in reducing dementia risk
Question 4
Artificial sweeteners (sweetener) and glycaemia - non-nutritive sweeteners (NNS) (artificial sweeteners) do not contain calories and are thereby presumed to be inert and not elicit a postprandial glycaemic response…however, new evidence challenges these assumptions. See GPnotebook for an update with respect to use of NNS and glycaemia implications, and risk of cardiovascular disease: Non-nutritive sweeteners (NNS) and glycaemia
4) With respect to artificial sweeteners, which statement is false?
- study evidence with respect to artifical sweeteners showed that impacts on the gut microbiome are causally linked to elevated glycaemic response
- study evidence showed that consumption of artificial sweeteners (especially aspartame, acesulfame potassium, and sucralose) were associated with increased risk of cardiovascular, cerebrovascular, and coronary heart diseases
- human gastrointestinal tract harbors thousands of microorganisms that play critical roles in multiple aspects of human physiology and pathologies, including cardiometabolic health
Question 5
Polypill in reducing cardiovascular disease risk - the SECURE trial investigated the use of a polypill containing aspirin, a statin and an ACE inhibitor versus usual care in patients with known cardiovascular disease. In the three-year study there was a more than 25% reduction in the primary endpoint (cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization) for the polypill group. There was no significant difference in lipid levels or blood pressure levels in the polypill group versus the usual care group. The only significant difference seems to be with compliance - could this be the only reason why the polypill "worked"?: Polypill in prevention of cardiovascular disease (CVD)
5) With respect to the SECURE trial using a polypill to reduce risk of cardiovascular disease, which statement is false?
- treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care
- the use of the polypill was associated with a significant reduction in LDL in comparison to placebo
- medication adherence as reported by the patients was higher in the polypill group than in the usual-care group
Question 6
DELIVER study – this important trial is summarised on GPnotebook.: DELIVER study - dapagliflozin in heart failure with mildly reduced or preserved ejection fraction
5) With respect to the DELIVER study, which statement is false?
- The dose of dapagliflozin used in the DELIVER study was 5mg
- in the DELIVER study, dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction
- a pre-specified analysis of DELIVER showed that benefit of dapagliflozin was consistent across range of frailty studied & improvement in health-related quality of life with dapagliflozin occurred early and was greater in patients with greater frailty

Round Up Email September 2022

Question 1

Question 2

Question 3

Question 4

Question 5

Question 6