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1st June 2023
The health status in Germany has improved over the last two decades, and life expectancy remains above the EU average despite the temporary reduction registered in 2020 that was caused by the Covid-19 pandemic.
Infection and death rates from Covid-19 in 2020 were lower in Germany than in most other EU countries. When measured as a share of GDP, health spending in Germany is the highest in Europe. The health system offers a generous benefits package, high levels of service provision and universal access to relatively high-quality and effective care. The Covid-19 pandemic revealed the challenges faced by federal systems in coordinating and managing such outbreaks.
In 2020, Germany registered a life expectancy of 81.1 years – six months above the EU average but still somewhat lower than in EU countries with the highest levels. The Covid-19 pandemic had less of an impact on life expectancy in Germany than in the EU as a whole, having fallen by 2.5 months in 2020 compared to an average of just over eight months across the EU. The leading causes of death in Germany in 2019 were ischaemic heart disease, stroke and lung cancer.
Around one in five adults smokes on a daily basis in Germany. While smoking rates have been declining, the growing popularity of e-cigarettes, particularly among young people, is a cause for concern. Adult and adolescent obesity rates are growing, and alcohol consumption among adults and 15-year-olds is considerably higher than the EU average.
In 2019, Germany spent €4,505 per capita on health – the highest among EU countries, and 28% more than the average (€3,523). Germany also spends a greater proportion of its GDP on health (11.7%) than any other EU country. The majority of health spending comes from public sources; out-of-pocket payments amount to only 12.7%, which is well below most other EU countries.
Mortality from preventable causes is lower in Germany than in the EU as a whole, reflecting the country’s effective public health and primary care system. Germany also has lower rates of death from treatable causes, owing to good access to effective treatments.
Access to care is generally good in Germany. Historically low rates for unmet needs rose during the Covid-19 pandemic when many non-urgent services were cancelled or postponed. One in seven people reported that they had to forgo needed care in 2020. However, the use of teleconsultations increased during the pandemic.
Despite well prepared health infrastructure and resources, Germany scaled up testing and laboratory capacities, intensive care unit beds and the health workforce. By the end of August 2021, around 60% of the population had received two Covid-19 vaccine doses.
OECD/European Observatory on Health Systems and Policies (2021), Germany: Country Health Profile 2021, State of Health in the EU, OECD Publishing, Paris/European Observatory on Health Systems and Policies, Brussels.
25th May 2023
The use of short-stay wards located in an emergency department (ED) and managed by emergency care clinicians, benefits patients by reducing their length of stay (LOS) and 28-day mortality risk, according to the findings of a retrospective study by Korean researchers.
Published in BMC Emergency Medicine, the researchers hypothesised that ED clinician care within the ESSW was more likely to reduce patient’s LOS in the department and without affecting overall clinical care. They retrospectively analysed adult patients who visited the ED at a tertiary academic hospital in Seoul.
The patients were divided into three groups: those admitted to the ESSW and treated within the ED (ESSW-EM); those admitted but treated by other departments (ESSW-Other) and those who were admitted to general wards (GW). The researchers had a single, co-primary outcome which was ED length of stay and 28-day mortality.
A total of 29,596 patients were included in the analysis, with 31.3% categorised as ESSW-EM and 59.8% as GW.
When comparing ED LOS, the researchers found that the shortest time was for those in the ESSW-EM group (mean 7.1 hours). The mean ED LOS was 8.0 hours and 10.2 hours in the ESSW-Other and GW groups respectively (p < 0.001 for both comparisons). In addition, 28-day hospital mortality was 1.9% for the ESSW-EM group and 4.1% for the GW group (p < 0.001).
Using multivariable logistic regression analyses, being in the ESSW-EM group was independently associated with a lower hospital mortality compared with both the ESSW-Other group (adjusted p = 0.030) and the GW group (adjusted p < 0.001).
With patients’ LOS being a potential surrogate marker for overcrowding, the authors suggested that admission to an ESSW, under the care of emergency care clinicians, is a potentially effective strategy to alleviate emergency department overcrowding and improve patient outcomes.
Emergency department boarding, or overcrowding, is known to increase both hospital LOS and mortality. Consequently, in an effort the alleviate overcrowding, many Westernised countries have introduced a waiting time target, to reduce the time spend by patients in the department. This target has often been set at four hours and there is some evidence that it does reduce mortality rates. Nevertheless, a systematic review in 2010 concluded that the introduction of such targets, has not resulted in a consistent improvement in care.
An alternative proposed solution to reduce ED overcrowding and the associated mortality risks, is to have short-stay units within the ED. These emergency department short-stay wards (ESSW) are specific areas within the department designed to provide short-term care for a selected group of patients and hopefully to alleviate overcrowding.
While a potentially promising approach, a systematic review in 2015 noted insufficient evidence to make any firm conclusions on either the effectiveness or safety of short-stay units compared with inpatient care. Nevertheless, other work has shown that use of an ESSW is associated with a low rate of subsequent ICU admission. In contrast, an ESSW designed to manage patients with cardiac problems, actually increased patient’s hospital LOS.
Despite the limitations of the evidence, no previous studies have explored the potential benefit of using emergency care clinical staff within the ESSW.
28th April 2023
Life expectancy in Belgium remains slightly above the EU average, but it temporarily fell sharply in 2020 because of deaths due to Covid-19.
While the Belgian health system provides good access to high-quality care, the Covid-19 pandemic highlighted important challenges with prevention and public health, the health workforce and quality of care in long-term care facilities for older people. The pandemic stimulated many innovative practices in Belgium that could be expanded to build a more resilient healthcare system.
Life expectancy in Belgium increased more than the EU average between 2010 and 2019, but fell by more than a year in 2020 because of deaths due to Covid-19. About 60% of the Covid-19 deaths in 2020 were among residents in long-term care facilities. As in many other countries, the mental health of many young people and adults in Belgium deteriorated greatly during the pandemic, with reports of anxiety and depression reaching much higher levels than in previous years.
Risk factors for health are major drivers of ill health and mortality in Belgium. While tobacco consumption has substantially decreased over the past two decades, 15% of adults were daily smokers in 2018. Nearly 30% of adults reported regular heavy alcohol consumption in 2018, a rate well above the EU average. About 16% of adults were obese in 2018, close to the EU average, but up from 12% in 2001. Overweight and obesity among 15-year-old adolescents have also increased to 17% in 2018, up from 11% in 2002.
Health spending per capita increased slowly between 2008 and 2019 and remains higher than the EU average. In 2019, health spending accounted for 10.7% of GDP, up from 9.6% in 2008, and also a higher share than the current EU average (9.9%). Public spending accounted for 77% of overall health spending – slightly less than the EU average of 80%.
Avoidable mortality was slightly lower than the EU average before the pandemic, but higher than in many other western EU countries. This suggests that more could be done to save the lives of people through health promotion and a reduction of risk factors and through better healthcare.
Although access to healthcare in Belgium is generally good, the Covid-19 pandemic significantly affected access to care in 2020: 22% reported forgone care during the first 12 months of the pandemic, which is close to the EU average of 21%. Growing use of teleconsultations helped maintain access to care during the pandemic.
Belgium was among the EU countries hardest hit by the Covid-19 pandemic in numbers of cases and deaths relative to its population size, particularly during the first wave. Belgium accelerated its vaccination campaign in the first half of 2021. By the end of August 2021, 70% of the population had received two doses (or equivalent) of a Covid-19 vaccine.
OECD/European Observatory on Health Systems and Policies (2021), Belgium: Country Health Profile 2021, State of Health in the EU, OECD Publishing, Paris/European Observatory on Health Systems and Policies, Brussels.
Life expectancy in Austria is higher than the EU average, but fell sharply in 2020 due to Covid-19 deaths.
While the Austrian health system generally provides good access to high-quality care, the Covid-19 pandemic underscored some structural issues, including the need to pursue reforms to overcome fragmentation and strengthen primary care.
A strong digital infrastructure offers Austria the potential to build a more integrated and resilient health system.
Although life expectancy in Austria in 2020 was more than half a year higher than the EU average, it fell by 0.7 year compared with 2019 because of the Covid-19 pandemic. Even before the pandemic, gains in life expectancy in Austria had slowed considerably between 2010 and 2019.
About 40% of all deaths in Austria in 2019 can be attributed to behavioural risk factors. Tobacco consumption among adults has fallen but remains slightly higher than the EU average. Alcohol consumption among adults in Austria is the second highest in the EU. Heavy alcohol consumption among adolescents is also higher than the EU average.
Spending on health per capita in Austria was the third highest in the EU in 2019. Austria spends substantially more than most countries on hospital inpatient care, while spending on prevention is lower than average. It also has relatively high numbers of physicians and hospital beds. While three quarters of all health expenditure is publicly funded, direct out-of-pocket spending by households is higher than the EU average.
Mortality from preventable and treatable causes in 2018 was lower in Austria than the EU average. Nevertheless, Austria lagged behind many other EU countries on preventable mortality, suggesting that more could be done to scale up prevention and reduce risk factors for cancer and other leading causes of death.
Access to healthcare is good in Austria, although Covid-19 created barriers to access. One in eight Austrians reported that they had forgone care during the first 12 months of the pandemic. Digital services helped to maintain access to care during the Covid-19 crisis: 35% of Austrians reported that they used teleconsultation services during the first year of the pandemic, which was slightly lower than the EU average.
Between March 2020 and August 2021, confirmed Covid-19 case numbers in Austria were similar to the EU average, although the death rate was lower. By the end August 2021, more than 60% of the population had received at least one dose of a Covid-19 vaccine, and 57% had received two doses or the equivalent. These proportions were close to the EU average.
OECD/European Observatory on Health Systems and Policies (2021), Austria: Country Health Profile 2021, State of Health in the EU, OECD Publishing, Paris/European Observatory on Health Systems and Policies, Brussels.
14th April 2023
Danish researchers have found that use of drugs affecting the renin-angiotensin-system (RAS) is associated with a lower risk of both acute exacerbations and death in patients with chronic obstructive pulmonary disease (COPD).
COPD remains a major public health problem with one analysis finding that globally in 2019, there were 212.3 million cases and which accounted for 3.3 million deaths. In addition, COPD is characterised not only by local pulmonary, but also by systemic inflammation which promotes the development of extra-pulmonary and cardiovascular co-morbidities. Although traditionally used in the management of hypertension, there is emerging evidence that RAS inhibitors such as angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) also have potential benefits in COPD patients. In fact, evidence from a retrospective analysis suggest that RAS inhibitors have dual cardiopulmonary protective properties, reducing the risk of myocardial infarction as well as COPD-related hospitalisation.
In the current study, the Danish researchers hypothesised that the use of RAS inhibitors could reduce the incidence of acute exacerbations of COPD as well as mortality in those with severe disease. Adopting a propensity-score matching approach, the team matched COPD patients prescribed a RAS drug with a similar cohort of COPD patients given bendroflumethiazide as an active comparator. The primary outcome was severe acute exacerbations of COPD within 12 months after study entry or death in the same period.
RAS inhibitor use and COPD outcomes
A total of 3029 patients with a median age of 72 years (69.1% female) and prescribed either an ACEi or ARB and propensity matched to a similar number prescribed bendroflumethiazide.
The use of either an ACEi or ARB was associated with a 14% lower risk of exacerbations or death compared to those using bendroflumethiazide (hazard ratio, HR = 0.86, 95% CI 0.78 – 0.95). This reduced risk was also evident in a sensitivity analysis of the propensity-score-matched population (HR = 0.89, 95% CI 0.83 – 0.94) and in an adjusted Cox proportional hazards model (HR = 0.93, 95% CI 0.89- 0.98).
The authors concluded that use of RAS inhibitor treatment lowered the risk of both acute exacerbations and death in those with COPD. However, they added the caveat that while there is a biologically plausible explanation for this finding, randomised controlled trials were needed to confirm this effect, given the observational nature of their study.
Vilstrup F et al. Renin-angiotensin-system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study. BMJ Open Respir Res 2023
21st March 2023
Levels of the inflammatory marker, high-sensitivity C-reactive protein (CRP) serve as a better predictor for the risk of future cardiovascular events and death in comparison to LDL cholesterol (LDLC), according to an analysis of data from three, large, cardiovascular trials by US researchers.
It has been recognised for many years that high-sensitivity CRP predicts the risk of future myocardial infarction and stroke in healthy men and this relationship also holds true for women. In addition, while hyperlipidaemia is a risk factor for cardiovascular disease, it is also known that addition of drugs with an anti-inflammatory effect, such as colchicine to statin therapy, also significantly reduces the risk of cardiovascular events in patients with chronic cardiac disease.
Given how both inflammation and elevated LDL cholesterol are important cardiovascular risk factors, because patients prescribed statins can still experience an adverse cardiovascular event, an important question is how to deal with this residual risk. In other words, should clinicians treat with additional lipid lowering therapy (to minimise the residual cholesterol risk) or use an anti-inflammatory agent (to lower the residual inflammatory risk)?
Using data from three large statin trials (PROMINENT, REDUCE-IT and STRENGTH) the US researchers compared the highest and lowest quartiles of high-sensitivity CRP and LDLC , to determine the best predictors of future major adverse cardiovascular events, cardiovascular death, and all-cause death.
High-sensitivity CRP and cardiovascular outcomes
A total of 31,245 patients were included and participants aged between 64 and 65 with the proportion of females ranging from 28 to 35%.
Combining data from the three trials showed that the presence of residual inflammatory risk was significantly associated with incident major adverse cardiovascular events (adjusted Hazard Ratio, aHR = 1.31, 95% CI 1.20 – 1.43, p < 0.0001) for the highest vs the lowest high-sensitivity CRP quartiles. This relationship was also true for cardiovascular mortality (aHR = 2.68, p < 0.0001) and all-cause mortality (aHR = 2.42, p < 0.0001).
However, when comparing the highest to lowest quartiles of LDL cholesterol, the relationship was non-significant for major adverse cardiovascular events (aHR = 1.07, p = 0.11) but was significant, albeit smaller, compared to high-sensitivity CRP, for cardiovascular death (aHR = 1.27, p = 0.0086) and all-cause mortality (aHR = 1.16, p = 0.025).
The authors concluded that in those already prescribed a statin, high-sensitivity CRP proved to be a stronger marker for the prediction of future cardiovascular events and death compared to LDL cholesterol levels. They added that their findings suggested that both aggressive lipid-lowering and inflammation-inhibiting therapies might be needed to further reduce atherosclerotic risk.
Ridker PM et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet 2023
15th March 2023
The presence of hypertension irrespective or whether or not it is controlled, in patients with obesity, increases the risk of all-cause mortality according to a large, population study by Singaporean and Australian researchers.
Hypertension is the leading cause of global cardiovascular disease and premature death with the World Health Organisation estimating that 1.28 billion adults aged between 30 and 79 have hypertension, two-thirds of whom, live in low and middle-income countries. It has also become clear that as body mass index increases, so too does the risk of hypertension. Although the prevalence of hypertension among those with obesity has been found to be above 70%, much less is known about the impact on mortality of having hypertension and whether the level of control exerts a mitigating effect.
In the current study, researchers collected data on obese patients, which was defined as adults with a body mass index (BMI) of ≥ 30.0 kg/m2. Furthermore, individuals were then stratified by their hypertensive status as either having controlled hypertension (CH) (< 140/90 mmHg) with antihypertensive use, uncontrolled hypertension (UCH) ( ≥ 140/90 mmHg) with and without antihypertensive use or normotensive. The main outcome measure was all-cause mortality.
Controlled and uncontrolled hypertension and all-cause mortality
A total of 16,386 individuals with obesity were included and of whom, just over half (53.1%) were normotensive, a quarter (24.7%) had CH with the remainder having uncontrolled disease. These individuals were then followed-up for a median of 7.3 years.
The presence of hypertension per se increased the risk of all-cause mortality (Hazard Ratio, HR = 1.28, 95% CI 1.14 – 1.44, p < 0.001). After adjustment for potential confounders, the researchers found that among obese patients with UCH, there was an increased all-cause mortality risk (HR = 1.34, 95% CI 1.13 – 1.59, p = 0.001), compared to normotensive individuals. However, there was also a significantly increased mortality risk for those with CH (HR = 1.21, 95% CI 1.10 – 1.34, p < 0.001). In fact, further adjustment of the regression model for chronic kidney disease, still gave rise to a significant risk of all-cause mortality in those with CH (HR = 1.17, p = 0.007).
The authors concluded that the excess mortality risk among obese patients, irrespective of whether their hypertension was controlled, should urge health care providers to optimise disease control and advocate weight loss to achieve better outcomes in obesity.
Kong G et al. A two-decade population-based study on the effect of hypertension in the general population with obesity in the United States. Obesity (Silver Spring) 2023
11th January 2023
Molnupiravir treatment in vaccinated, high-risk patients infected with COVID-19, failed to reduce both the rate of hospitalisation and death compared to usual care according to the results of a large, randomised trial by members of the PANORAMIC Trial collaborative group.
It is possible that the early treatment of COVID-19 infected patients with anti-viral agents, might prevent deterioration, speed up recovery and reduce the need for hospital admission. One such anti-viral is molnupiravir (EIDD-2801) and which was originally shown to be a potentially effective clinical candidate with high potential for monotherapy of seasonal and pandemic influenza virus infections. Nevertheless, early molnupiravir treatment in patients infected with COVID-19 and at least one risk factor for severe illness, was subsequently shown to reduce the risk of hospitalisation or death in unvaccinated adults. But with millions of individuals now vaccinated against COVID-19, it remains uncertain whether molnupiravir treatment is still an effective option in such patients. There is some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this is not conclusive. As a result, in the present study, researchers set out to establish the effectiveness of molnupiravir in vaccinated, high-risk, community patients at reducing hospital admission or death.
The study included community (i.e., non-hospitalised) patients aged 50 years and older, or 18 years and older with relevant comorbidities and who had COVID-19 symptoms within the previous 5 days, together with a positive PCR or rapid antigen test within the past 7 days. Eligible participants were randomly assigned (1:1) to receive molnupiravir 800 mg twice daily for 5 days plus usual care or usual care alone. The primary outcome was set as all-cause hospitalisation or death within 28 days of randomisation.
Molnupiravir treatment and adverse COVID-19 outcomes
A total of 25,783 individuals with a mean age of 56·6 years (58.5% female) were randomised to molnupiravir (12, 821) or usual care. Additionally, 69% of the whole cohort had comorbidities and 94% had received at least three doses of a COVID-19 vaccine.
Hospitalisations or deaths were recorded in 1% of both groups (adjusted odds ratio, aOR = 1·06, 95% CI 0·81 – 1·41, p = 0.33). Moreover, in subgroup analyses, there were no significant differences when assessed on several factors including the presence/absence of co-morbidities, age (< 65 vs > 65), or among those who were immunocompromised.
Despite no difference in the primary outcome, molnupiravir treatment was associated with a reduction in the median time from randomisation to first recovery (hazard ratio, HR = 1·36, 95% CI 1·32 – 1·40).
The authors concluded that in a highly vaccinated population at high risk of complications from COVID-19, the avoidance of hospitalisation and death was primarily achieved via extensive vaccination. They added that the benefits of molnupiravir in terms of a faster recovery time need to be considered in the context of several other relevant factors including the prevailing disease, burden on health-care services, drug-acquisition cost, social circumstances, cost-effectiveness, and opportunity costs.
Butler CC et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet 2022.
11th November 2022
Using either a lower, intermediate or higher oxygen saturation target does not affect 28-day mortality or the number of mechanical ventilation-free days among critically ill patients according to the findings of the PILOT randomised trial by US researchers.
Invasive mechanical ventilation is an intervention that is frequently used in patients with acute respiratory failure, and which can be hypoxic or hypercapnic. Nevertheless, such patients are at a high risk of death with one study finding that nearly half (44%) of patients receiving mechanical ventilation for longer than 14 days died. The fraction of inspired oxygen is adjusted in mechanically ventilated patients to maintain arterial oxygen saturation although the oxygenation target which provides the best clinical outcomes for patients remains unclear. For example, too much oxygen (hyperoxemia) can result in acute lung injury, whereas hypoxia is associated with tissue damage and increased in-hospital mortality. Moreover, trial data on the optimal oxygen target are conflicting. For instance, using either a low-normal or high-normal showed no difference in organ dysfunction, whereas another study found that a conservative protocol for oxygen therapy versus conventional therapy resulted in lower intensive care mortality. In contrast, use of a higher target, i.e., more liberal oxygen therapy improved 28-day mortality compared to a conservative-oxygenation strategy.
For the present PILOT study, patients within an emergency and critical care department were randomised to a lower target for oxygen saturation (90%), an intermediate target (94%) or a higher target (98%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilation-free days), defined from the day of ventilation through to day 28. The sole secondary outcome was death from any cause by day 28.
Oxygen saturation target and mortality
A total of 2541 patients with a median age of 53.3 years (45.4% female) were randomised to either the lower (808), intermediate (859) or higher oxygen target (874).
The median number of ventilation-free days ranged from 20 to 21 for the three groups and was not statistically different (p = 0.81). Similarly, there were no significant differences between the groups for in-hospital mortality at day 28. In addition, there were no differences in the incidence of adverse cardiac events e.g., arrhythmia or myocardial infarction.
The authors concluded that ventilation-free days did not differ depending on the oxygen saturation target.
Semler MW et al. Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation. N Eng J Med 2022
4th November 2022
A higher level of plant omega-3 levels in ambulatory heart failure patients significantly reduced all-cause mortality and first heart failure hospitalisation risk compared to levels of marine-based omega-3 according to the findings of a study by Spanish researchers.
The supplementation with marine-based omega-3 fatty acids can provide a small beneficial advantage in terms of mortality and cardiovascular-related hospital admission in patients with heart failure. Other work has suggested that omega-3 fatty acid supplements also offer benefits on recurrent heart failure hospitalisation although further work is required to confirm these findings. However, not everyone eats fish or wants to take supplements and for such individuals, omega-3 fatty acids can be obtained through the diet via other sources. For example, plant omega-3 sources include alpha-linolenic acid (ALA) which is present in flaxseed and walnut oil. But whether this plant-based source of fatty acids provides the same benefits to heart failure patients as marine-based acids is unclear.
In the present study, the Spanish team speculated that regular consumption of ALA foods would provide a beneficial effect in terms of morbidity and mortality for patients with heart failure. To provide a more accurate measure of intake, rather than relying on self-reporting, the Spanish team assessed ALA levels in serum phospholipids which provides a more objective measure of ALA intake. For comparative purposes, they also measured serum levels of marine-based omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The team recruited patients who attended a heart failure unit with a tertiary hospital in Barcelona. The primary outcome was a composite of all-cause mortality or first heart failure hospitalisation although the researchers also separately examined the components of the composite as secondary outcomes. The levels of ALA were split into quartiles and multivariable regression analysis was used and focused on a comparison of the lowest (Q1) versus the highest (Q2 – Q4) levels.
Plant omega 3 levels and heart failure outcomes
A total of 905 patients with a mean age of 67 years (31.7% female) were included and followed up for a median of 2.4 years.
The primary endpoint occurred in 184 patients during follow-up including141 heart failure hospitalisations. When comparing ALA levels between Q1 and Qs 2-Q4, there was a 39% lower risk of the primary endpoint (Hazard ratio, HR = 0.61, 95% CI 0.46 – 0.81, p = 0.001). There were similarly significant reductions for the components of the composite, i.e., all-cause mortality (HR = 0.58, 95% CI 0.41 – 0.82, p = 0.002) and first heart failure hospitalisation (HR = 0.58, 95% CI 0.40 – 0.84).
Interestingly, when looking at the combined levels of EPA and DHA there was no significant effect on the primary endpoint when comparing Q1 with Q2 – Q4 (HR = 1.11, 95% CI 0.82 – 1.51, p = 0.502). The effect on both all-cause mortality and heart failure hospitalisation were also non-significant.
The authors concluded that elevated levels of plant omega-3 fatty acids in serum were related to a lower risk of incident adverse clinical outcomes in patients with heart failure.
Lazaro I et al. Relationship of Circulating Vegetable Omega-3 to Prognosis in Patients With heart failure J Am Coll Cardiol 2022