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6th April 2023
US researchers have found that achieving 8,000 daily steps on only one to two days in a week appears to provide the same all-cause mortality benefit as undertaking the same number of steps for between 3 and 7 days per week.
It has become increasing recognised that a greater number of daily steps is significantly associated with a lower all-cause mortality. However, the mortality benefits appear to plateau for adults older than 60 years at approximately 6000–8000 steps/day and between 8000 – 10 000 steps/day for those under 60 years. Nevertheless, with a lack of time identified as a barrier to undertaking more physical activity by nearly two-thirds of respondents in a recent survey, whether the same mortality benefits could be achieved through undertaking 8,000 daily steps but on less days remains uncertain.
In the current study, researchers set out to evaluate the dose-response association between the number of days an individual takes 8,000 or more daily steps and mortality among US adults. The study included a representative sample of US participants aged 20 years or older, who wore an accelerometer for 1 week. These individuals were then categorised into three groups, based on the number of days that they undertook 8,000 or more daily steps: 0 days, 1 – 2 days and 3 – 7 days. The main outcome of interest was all-cause and cardiovascular mortality over a 10-year follow-up period and the results adjusted for potential confounders such as age, sex, race and ethnicity, insurance status, marital status, smoking, comorbidities and average daily step counts.
One to two days of 8,000 daily steps and all-cause mortality
A total of 3,101 participants with a mean age of 50.5 years (51% female) were included in the analysis. Overall, 20.4% did not take 8,000 steps or more any days of the week, 17.2% took 8000 steps or more 1 to 2 days per week and 62.5% undertook 8000 steps or more 3 to 7 days per week.
Over the 10-year period of follow-up, compared to those who did not walk 8,000 daily steps on any day per week, the all-cause mortality risk was lower among those who took 8000 or more daily steps on one to two days per week (adjusted risk difference, aRD = -14.9%, 95% CI -18.8% to -10.9%). However, among those walking 8,000 or more daily steps for between 3 and 7 days per week, the risk difference was similar (aRD = -16.5%, 95% CI, -20.4% to -12.5%). There were also similar reductions in cardiovascular mortality between the one to two day and three to seven day groups.
The authors concluded that individuals may receive substantial health benefits by walking just a couple days a week.
Citation
Inoue K et al. Association of Daily Step Patterns With Mortality in US Adults. JAMA Netw Open 2023
Nirmatrelvir treatment for patients with COVID-19 has been found to also reduce the risk of developing most post-COVID-19 condition symptoms.
A study by US researchers from St Louis, Missouri has revealed that nirmatrelvir treatment during the acute phase of a COVID-19 infection, reduces the subsequent risk of developing post-COVID-19 condition or long covid.
Post-COVID-19 condition or long COVID is an often debilitating illness that occurs in at least 10% of those infected with the virus and is estimated to affect 65 million people worldwide.
In a clinical trial, nirmatrelvir treatment for symptomatic, unvaccinated, non-hospitalised adults at high risk for progression to severe COVID-19, reduced the risk of disease progression by 89% compared to placebo.
Given that to date, there are no approved treatments for post-COVID-19 condition, it is important to examine whether the use of the available anti-viral therapies are able to reduce the risk of developing the condition.
Thus far, the evidence suggests that COVID-19 vaccines might have protective and therapeutic effects on long COVID, though more robust data are required to confirm this effect.
In the current study, the US researchers examined whether nirmatrelvir (Paxlovid) treatment for COVID-19 was associated with a reduced risk of developing post-COVID-19 condition.
They used a US database to identify patients who had a positive COVID-19 test, who were not hospitalised, had at least one risk factor for progression to severe COVID-19 illness and received oral nirmatrelvir.
This group was then compared to one in which no COVID-19 anti-viral or antibody treatment had been given during the acute phase of their illness.
A total of 281,793 patients with a mean age of 61.9 years (86% male) were treated with the drug.
In comparison to the control group, anti-viral treatment was associated with a 24% reduced risk of developing post-COVID-19 condition (relative risk, RR = 0.74, 95% CI 0.72 – 0.77).
Drug therapy was also associated with reduced risk of post-acute death (Hazard ratio, HR = 0.53, 95% CI 0.46 – 0.61) and post-acute hospitalisation (HR = 0.76, 95% CI, 0.73 – 0.80). Nirmatrelvir treatment was associated with reduced risk of post-COVID-19 condition, in those who were unvaccinated, vaccinated and vaccine boosted, as well as individuals who had a re-infection.
The authors concluded that nirmatrelvir treatment was associated with reduced risk of post-COVID-19 condition regardless of vaccination status and history of prior infection.
Citation
Xie Y et al. Association of Treatment With Nirmatrelvir and the Risk of Post-COVID-19 Condition. JAMA Intern Med 2023.
In a study using deep learning-enabled image segmentation of cardiac magnetic resonance imaging data, US researchers identified how variation in the left ventricle (LV) sphericity index in otherwise normal hearts, predicts the risk for cardiomyopathy and related outcomes such as atrial fibrillation.
Dilation of cardiac chambers and or a decline in systolic function are key indicators of disease and which can be assessed using conventional imaging modalities to quantify such changes. Moreover, deep neural networks have shown a great potential in image pattern recognition and automated methods achieve a performance on par with human experts in analysing cardiovascular magnetic resonance images and deriving clinically relevant measures. Cardiomyopathies of different aetiologies can often result in a similar end-stage phenotype of a more round, spherical ventricle. In fact, in patients with cardiac diseases, a greater sphericity of the left ventricle, has, for example, been shown to be an independent predictor of 10-year survival following an acute myocardial infarction. In the current study, researchers thought that even among those with normal heart function, there was likely to be variation in cardiac sphericity, in particular, sphericity of the left ventricle and that this may serve as marker of cardiac risk, especially among those with an underlying genetic risk.
Using automated deep-learning segmentation of cardiac magnetic resonance imaging (MRI) data, the researchers estimated and analysed the sphericity index in patients who were part of the UK Biobank database but excluded those with either abnormal left ventricular size or systolic function.
Cardiac sphericity and risk of cardiomyopathy
In a total of 38,897 participants, the researchers calculated that for one standard deviation increase in the sphericity index, or roundness of the heart, there was an associated 47% increased incidence of cardiomyopathy (hazard ratio, HR = 1.47, 95% CI 1.10 – 1.98, p = 0.01). In addition, the same increase in the sphericity index, was associated with a 20% increased incidence of atrial fibrillation (HR = 1.20, 95% CI 1.11 – 1.28, p < 0.001) and which was independent of clinical factors and traditional magnetic resonance imaging (MRI) measurements. In contrast, similar increases in the sphericity index were non-significantly associated with the risk of both heart failure (p = 0.3) and cardiac arrest (p = 0.70).
The team also identified four loci associated with sphericity at genome-wide significance and concluded that the variation in left ventricular sphericity in otherwise normal hearts, predicts the risk for cardiomyopathy and related outcomes and is caused by non-ischaemic cardiomyopathy.
Citation
Vukadinovic M et al. Deep learning-enabled analysis of medical images identifies cardiac sphericity as an early marker of cardiomyopathy and related outcomes. Med 2023
5th April 2023
Neutrophil CD64 level measurement in emergency department (ED) patients with a suspected bacterial infection, has a both a high specificity and positive predictive value for diagnosing a bacterial infection. However, low levels cannot be used to rule out these infections, according to the findings of a study by the COVPACH study group.
Infections are a common ED presentation that require diagnostic biomarkers to enable the differentiation between those of a bacterial or viral origin. C-Reactive Protein (CRP) is one such marker that appears to act as a surveillance molecule for altered self and certain pathogens. Levels of CRP increase very rapidly in response to trauma, inflammation, and infection although CRP has been found to be neither sufficiently sensitive or specific to identify bacterial infections, particularly with lower respiratory tract infections. Although other markers such as the white blood cell (WBC) count and erythrocyte sedimentation rate can be used, the WBC count has a low sensitivity and specificity for a bacterial infection. An alternative marker is the neutrophil CD64 level with one meta-analysis concluding that it could be a promising and meaningful biomarker for diagnosing bacterial infection. In addition, while neutrophil CD64 demonstrates moderate performance in diagnosing sepsis in critically ill patients, whether it helps to diagnose bacterial infections within the ED where an answer is rapidly needed, is less clear and was the purpose of the current study.
Researchers examined the value of neutrophil CD64 (nCD64) in a study with COVID-19 suspected patients who visited the ED and for which a definitive diagnosis was made. Blood samples were analysed within 2 hours after presentation and patients categorised as having either a bacterial, viral, and non-infectious disease. The team then determined the diagnostic value of nCD64 and compared this to those of CRP and WBC counts.
Neutrophil CD64 as a biomarker for bacterial infections
A total of 182 patients with a median age of 63 years (52.7% male) were included and of whom, 43% had a confirmed bacterial infection and 35% a viral infection.
The median nCD64 level was higher in bacterial compared to viral infection (p = 0.004) and the non-infectious group (p < 0.0001). However when analysing the area under the receiver operating characteristics curve, there were no significant differences between the three biomarkers.
Using a cut-off of 9.4 units for nCD64, the corresponding positive predictive value was 1.00 and the specificity was 1.00 although the sensitivity was only 27%.
The authors concluded that nCD64 had a high specificity and positive predictive value for diagnosing a bacterial infection but noted how a low nCD64 could not be used to rule out a bacterial infection. They added that nCD64 should be combined with additional tests to form an algorithm that adequately diagnoses infectious diseases.
Citation
van de Ven NLM et al. Point-of-care neutrophil CD64 as a rule in diagnostic test for bacterial infections in the emergency department. BMC Emerg Med 2023
Among patients presenting at an emergency department (ED) with cannabis intoxication, almost half presented with cardiovascular (CV) symptoms according to the findings of a retrospective analysis by researchers from Amsterdam, the Netherlands.
In a study with 10,000 students, cannabis was rated as the most favourable most commonly used tobacco product the past 30 days and also perceived as the least harmful when compared to electronic cigarettes and cigarettes themselves. However, cannabis use is not without risks and one systematic review found that the data from 29 observational studies, suggested an association between cannabis-based product use and cardiovascular disease, with the strongest evidence for ischaemic heart disease. There is also data to suggest that cannabis use is associated with an increased risk of cardiac dysrhythmia, which is rare but may be life-threatening. As a result, there remains some uncertainty over whether patients who present at an ED with cannabis intoxication should undergo a full cardiovascular evaluation.
In the current study, the Dutch team retrospectively analysed data on a convenience sample of all self-reported cannabis-intoxicated adult patients who presented at an Amsterdam ED. Individuals who were intoxicated due to mixed recreational drug use were excluded and presenting symptoms were categorised as either CV-related (e.g., palpitations, chest pain and syncope) or non-cardiovascular (like nausea and vomiting).
Cardiovascular symptoms and cannabis intoxication
A total of 1689 individuals with a mean age of 31.9 years (62.4% male) were included in the study.
Overall, 47.2% presented with cardiovascular symptoms and which included palpitations (57.6%), chest pain (12.9%) and syncope (36.8%). Among those with CV-related symptoms, 8 had complications including ST elevation myocardial infarction, non-ST elevation myocardial infarction, atrial fibrillation and AV-nodal re-entrant tachycardia. Other ECG abnormalities observed were ischaemic ECG changes, first-degree atrioventricular block, premature atrial complexes, ventricular extrasystoles, prolonged corrected QT interval, and a Brugada type 1 pattern. Fortunately, all of these resolved spontaneously during the observational period.
The authors concluded that while the clinical relevance of cardiovascular symptoms is largely unknown, cannabis-intoxicated patients should have a cardiac evaluation, and symptoms should not just be considered benign.
Citation
Gresnigt F et al. Incidence of cardiovascular symptoms and adverse events following self-reported acute cannabis intoxication at the emergency department: a retrospective study. Emerg Med J 2023
Administration of intra-vesical tranexamic acid to a Foley catheter in patients with gross haematuria, prior to continuous bladder irrigation, reduced both the length of stay in the emergency department (ED) and the duration of catheter placement, according to a before and after study by Korean researchers.
Macroscopic or gross haematuria is a commonly seen condition in the ED and for which there are a variety of causes. In gross haematuria, it is necessary to ensure that patients are not in urinary retention due to clot formation and in cases of clot retention, a three-way Foley catheter is used, to allow irrigation fluid to be passed through the bladder, clearing clots from the site of bleeding. Tranexamic acid has haemostatic effects and hinders fibrinolysis and clot degradation and while the drug has been used to control bleeding in conditions such as epistaxis, whether it can affect spontaneous bleeding from the lower urinary tract is less clear. However, to date, one small study in which bladder irrigation, local intra-vesical tranexamic acid and placebo were injected into the bladder via Foley catheter, found that the drug could significantly reduce the volume of required serum for bladder irrigation to clear urine.
Based on these encouraging preliminary findings, in the current study, the Korean team hypothesised that the use of tranexamic acid in those with gross haematuria, would reduce the duration of patient’s stay in the ED as well as the length of time for which Foley catheter placement was required. They conducted a ‘before’ and ‘after’ retrospective single-centre study, and examined the impact of using tranexamic acid in patients after a certain cut-off date (March 2022) and compared outcomes for patients before the specified date, i.e., those for whom tranexamic acid had not been used. The team set the primary outcomes as the length of stay in the ED and the duration of Foley catheter placement. The secondary outcomes were the admissions and the revisits for continuous bladder irrigation within 48 h after discharge.
Intra-vesical tranexamic acid and duration of ED stay
A total 159 patients with a mean age of 79.4 years (93.5% male) were included, with 86 in the ‘after’ group.
The results showed that the median length of stay in the ED was significantly shorter in the ‘after’ group (274 vs 411 minutes, p < 0.001). In addition, the median duration of the Foley catheter placement was also shorter (145 vs 308 minutes, p < 0.001).
There were also a lower proportion of ED visits among those given tranexamic acid (2.3% vs 12.3%, p = 0.031) as well as a trend towards less hospital admissions (29.1% vs 45.2%, p = 0.052).
The authors concluded that a reduction in length of stay of gross haematuria patients was observed after the implementation of intra-vesical tranexamic acid injection via a Foley catheter and called for further studies to confirm these findings.
Citation
Choi H et al. Impact of intravesical administration of tranexamic acid on gross hematuria in the emergency department: A before-and-after study. Am J Emerg Med 2023
An analysis by Korean researchers of patients admitted to an emergency department (ED) with a rib fracture diagnosed on chest radiography has identified important fracture characteristics indicative of significant intra-thoracic and intra-abdominal injuries that require assessment by chest computed tomography (CT).
The ribs are frequently affected by a blunt or penetrating injury to the thorax and within an ED, it is vital for the interpreting radiologist to not only identify the presence of rib injuries but also alert the clinician about organ-specific injury. A CT chest plays a major role for the in-vivo assessment of the body composition at the tissue/organ level and is the imaging modality of choice for accurate delineation of rib fractures and associated internal injuries. However, the main limitation associated with the use of CT scan is the ionising radiation patient burden. Consequently, identification of rib fracture features that could enable more appropriate use of a chest CT for such patients are warranted.
In the current study, the Korean team retrospectively analysed adult patients diagnosed with rib fracture due to blunt chest trauma that was diagnosed based on chest radiography and who underwent a chest CT examination. The researchers set the primary outcomes as intra-thoracic and intra-abdominal injuries that could be identified on a chest CT.
Rib fracture characteristics and need for a chest CT
A total of 401 patients with a mean age of 58 years (29.5% female) were included and of whom, 279 had any intra-thoracic or intra-abdominal injuries.
Overall, there was a higher number of rib fractures in those who sustained significant internal injuries (p < 0.001) and a higher level of bilateral fractures (p = 0.001).
In regression analysis, the number of fractures (adjusted odds ratio, aOR = 1.44, 95% CI 1.16 – 1.78), lateral fractures (aOR = 2.80) and posterior rib fractures (aOR = 3.18) were all independently associated with intra-thoracic and intra-abdominal injuries. Other factors also independently associated with such internal injury were the requirement of O2 supplementation, mechanical ventilator use, requirement of transfusion, pelvic bone fracture and extremity fracture.
The authors concluded that among blunt trauma-induced rib fracture patients, posterior and lateral fractures, more than three fractures, the need for O2 supplementation were the most important factors indicating the need for chest CT to identify intra-thoracic and intra-abdominal injuries in the emergency department.
Citation
Kim W et al. Characteristics of rib fracture patients who require chest computed tomography in the emergency department. BMC Emerg Med 2023
3rd April 2023
In a prospective study, Chinese and UK researchers have found that long-term exposure to high levels of road traffic noise (RTN), especially when levels of air pollution are also increased, is associated with an increased risk for the development of hypertension.
Hypertension is the leading cause of cardiovascular disease and premature death worldwide with one estimate suggesting that 349 million in high-income countries are affected by the condition. While modification of lifestyle factors such as a reduced intake of sodium, stopping smoking and increased physical activity are an integral part of the overall management strategy for the disease, it has become recognised that road traffic noise exposure is associated with increased risk of premature arteriosclerosis, coronary artery disease, and stroke. Moreover, the World Health Organisation (WHO) has suggested that there is high quality evidence linking road traffic road and ischaemic heart disease. However, while the WHO has found evidence linking noise from air, road, or rail traffic with hypertension, they considered the quality of the supportive evidence to be ‘very low’. Although some data indicates that exposure to RTN increases both systolic and diastolic blood pressure, it remains uncertain if exposure might actually cause hypertension.
In the current study, researchers examined information held in the UK Biobank to evaluate the association between long-term RTN exposure with incident primary hypertension. The RTN level was estimated with common noise assessment methods and the development of hypertension through linkage with medical records.
Road traffic noise and incident hypertension
A total of 246,447 individuals with mean age of 55 years (54.6%) were included in the analysis. Over a median follow-up period of 8.1 years, there were 21,140 cases of incident primary hypertension recorded.
In fully adjusted models for continuous exposure to RTN, there was 7% increase in newly diagnosed hypertension per 10 dB [A] increment in the mean weighted average 24-hour road traffic noise level (hazard ratio, HR = 1.07, 95% CI 1.02 – 1.13). Interestingly, exposure to the highest level of RTN (> 65 db[A]), and the highest levels of air pollution, based on both fine particles and nitrogen dioxide, posed the greatest risk for incident hypertension (HR = 1.22 for fine particles, HR = 1.18 for nitrogen dioxide).
The authors concluded that long-term exposure to road traffic noise was associated with an increased incidence of primary hypertension and that this effect was stronger in presence of higher air pollution.
Citation
Huang J et al. Road Traffic Noise and Incidence of Primary Hypertension: A Prospective Analysis in UK Biobank. JACC Adv 2023
Data presented at the 31st European Congress of Psychiatry (EPA 2023) showed that in patients with treatment-resistant major depressive disorder, esketamine nasal spray achieved significantly higher rates of remission as early as 6 weeks after starting therapy compared to the use of extended-release (XR) quetiapine.
In the World Health Organization European Region, depression is estimated to affect roughly 33.4 million people. In addition, a US study of 36,309 adults reported that the 12-month and lifetime prevalence’s of major depressive disorder were 10.4% and 20.6%, respectively.
Treatment-resistant depression (i.e., failure to respond to ≥2 treatments) affects 10-30% of those with major depressive disorder, and is associated with considerable morbidity and mortality. Esketamine nasal spray has been found when used in conjunction with an antidepressant to induce a significantly higher reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) score compared to placebo and an antidepressant.
Furthermore, antipsychotics are a potentially useful adjunct in treatment-resistant depression with a 2019 Cochrane review concluding that addition of an antipsychotic such as quetiapine to current antidepressant therapy, improved depressive symptoms over the short-term. But how esketamine compares to agents such as quetiapine is unclear and the subject of the study presented at EPS 2023.
The findings presented at EPA 2023 are from the ESCAPE-TRD trial which directly compared esketamine with quetiapine XR in addition to a selective serotonin re-uptake inhibitor/serotonin-norepinephrine re-uptake inhibitor (SSRI/SNRI), in patients with treatment-resistant major depressive disorder, over 32 weeks.
In the trial patients were randomised 1:1 to either esketamine or quetiapine plus an antidepressant and examined the effect of both on remission (defined as a MADRAS score < 10) and response (defined as a > 50% improvement in MADRAS score from baseline).
Esketamine nasal spray and treatment outcomes
A total of 676 patients were randomised to either quetiapine (340) or esketamine.
At Week 32, 55% of esketamine and 37% of quetiapine patients achieved remission. However, a significantly higher proportion of patients given esketamine achieved remission from week 6 (p = 0.008) onwards and a response from day 15 (p < 0.001).
The most common adverse effects from esketamine leading to treatment discontinuation were dizziness, dissociation and vomiting.
The authors concluded that an esketamine nasal spray use in patients with treatment-resistant depression led to a higher response and rate of remission over time compared to quetiapine XR.
Citation
Reif A. et al., Esketamine nasal spray shows higher remission and response rates over 32 weeks of treatment compared with quetiapine extended-release in patients with treatment resistant depression: Results from ESCAPE-TRD, a randomised, phase IIIb clinical trial. Presented at EPA 2023, March 25-28. Poster PO0067 (under oral communication 8).
31st March 2023
Researchers from the university of California found that drinking caffeinated coffee did not significantly increase the level of premature atrial contractions compared to avoidance of such drinks.
Both tea and coffee are the most widely consumed caffeinated beverages around the world. However, it is widely assumed that caffeinated drinks have pro-arrhythmic effects and which produce premature cardiac contractions, known as atrial and ventricular ectopy. In fact, it has become recognised that the presence of these premature atrial contractions, can help predict new-onset atrial fibrillation. Furthermore, an increased frequency of premature ventricular contractions has been linked to a higher incidence of congestive heart failure and mortality. Whether or not caffeinated products increase the risk of arrhythmias, is not well defined, although a 2013 systemic review concluded that caffeine exposure does not increase the risk of atrial fibrillation and that low-dose caffeine may even exert a protective effect. Caffeinated coffee has also been shown to have additional health benefits such as improved physical activity performance but may reduce sleep duration.
In the current study, the US researchers examined the acute effects of coffee consumption on several factors including cardiac ectopy, physical activity, sleep, and glucose levels by using continuously recording, wearable sensors. The study was conducted over a 14-day period and during this time, participants were randomly assigned to either consume or avoid, caffeinated coffee, with avoidance continued for two consecutive days. The team set the primary outcome as the mean number of daily premature atrial contractions and compared this figure with those recorded on days without coffee.
Caffeinated coffee and health outcomes
A total of 100 adults with a mean age of 39 years (51% women) were included in the study.
Consumption of caffeinated coffee gave rise a mean of 58 daily premature atrial contractions compared to 53 such events when the beverage was not taken (rate ratio, RR = 1.09, 95% CI 0.98 – 1.20, p = 0.10). In addition, use of caffeinated coffee led to 154 premature ventricular contractions compared to 102 on avoidance days (RR = 1.51, 95% CI 1.18 – 1.94).
On coffee drinking days, individuals also had a higher mean number of daily steps (10,646 vs 9,665), a lower mean number of nightly sleep minutes (397 vs 432 minutes) but similar levels of serum glucose.
The authors concluded that consumption of caffeinated coffee did not result in significantly more daily premature atrial contractions compared to days when the drink was avoided. They added that the secondary outcome data, e.g. higher premature ventricular contractions, more physical activity and less sleep, should be interpreted as hypothesis-generating.
Citation
Marcus GM et al. Acute Effects of Coffee Consumption on Health among Ambulatory Adults. N Eng J Med 2023