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Take a look at a selection of our recent media coverage:

Molnupiravir treatment fails to reduce adverse outcomes among high-risk vaccinated patients

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.

Citation
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.

Oxygen saturation target does not affect mortality in mechanical ventilation

11th November 2022

Different oxygen saturation targets used for critically ill patients receiving mechanical ventilation have no impact on 28-day mortality

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.

Citation
Semler MW et al. Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation. N Eng J Med 2022

Higher plant omega-3 levels reduce death and hospitalisation risk in heart failure

4th November 2022

Higher plant omega-3 levels in heart failure (HF) patients reduces mortality and first HR hospitalisation risk more than marine-based omega-3

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.

Citation
Lazaro I et al. Relationship of Circulating Vegetable Omega-3 to Prognosis in Patients With heart failure J Am Coll Cardiol 2022

Higher cystatin C levels associated with increased mortality in sepsis

17th October 2022

Higher cystatin C levels and kidney function derived measures upon ICU admission are associated with increased 90-day mortality in sepsis

Cystatin C (CC) is a serine protease inhibitor that can be used as a marker of glomerular filtration rate (GFR). In fact, there is a suggestion that measurement of cystatin C should be used for the initial prediction of GFR of a patient and among critically ill patients, serum CC levels significantly outperforms serum creatinine for the detection of an impaired GFR. Moreover, other work has shown that CC-based estimates of GFR in both the elderly and ethnically diverse populations in comparison to serum creatinine, was a better predictor of all-cause mortality. While GFR derived estimates from either CC or creatinine generally agree, a decrease in the CC estimate compared to that of creatinine has been suggested to be due to what has been described as shrunken pore syndrome (SPS). It has since been recognised that SPS has been associated with a substantial increase in mortality or morbidity in all investigated populations.

However, whether cystatin C-based estimates of GFR and SPS are linked to a higher mortality among intensive care unit (ICU) patients with sepsis is uncertain and was the subject of the present study by Swedish researchers. The team undertook a post hoc analysis of data from the FINNAKI study which was a prospective observational study of acute kidney injury patients. For the present analysis, included patients were those with severe sepsis either upon ICU admission or which developed during the period of study. Plasma samples were used to measure both cystatin C and creatinine levels and from which GFR estimates were calculated. The primary outcome was 90-day mortality, whereas secondary outcomes were the development of acute kidney injury (AKI) between 12 and 5 days after ICU admission and renal replacement therapy. CC plasma levels estimated GFR based on CC and creatine were divided into quartiles.

Cystatin C measurements and mortality

A total of 802 patients with a mean age of 65 years (35.9% female) were included. The presence of SPS was present in 9.9% of patients when using an estimated GFRCystatin to GFRcreatinine cut-off ratio of 0.6 and 20% when the cut-off was set at 0.70. A total of 176 patients developed AKI between 12 hours and 5 days after ICU admission.

For plasma CC levels in the highest quartile, there was a positive and significant association with increased 90-day mortality compared to the lowest quartile (hazard ratio, HR = 4.15, 95% CI 2.17 – 7.91, p < 0.001). Similarly, there was a significant association with 90-day mortality for the lowest quartile of CC estimated GFR compared to the highest (HR = 4.45, 95% CI 2.28 – 8.68, p < 0.001). The association with SPS was also significant whether the cut-off was 0.6 or 0.70. In contrast, there was no significant association between 90-mortality and creatinine-based GFR estimates. Even after corticosteroid use in the treatment of septic shock, the associations for serum CC and estimated GFR remained significant although the association for SPS with a cut off of 0.6 was no longer significant (p = 0.14). When the researchers if the association between CC levels and 90-mortality were also linked to the development of AKI within 5 days, the analysis revealed how this association was maintained for the highest quartile of serum CC levels (HR = 4.09, 95% CI 2.14 – 7.80, p < 0.001), as well as CC estimated GFR and SPS.

The authors concluded that higher cystatin C levels together with a reduced CC-based estimate of GFR and the presence of SPS in patients with SPS in ICU was associated with a higher 90-day mortality and that a higher incidence of AKI does not explain this association.

Citation
Linne E et al. Cystatin C and derived measures of renal function as risk factors for mortality and acute kidney injury in sepsis – A post-hoc analysis of the FINNAKI cohort J Crit Care 2022

Severe vitamin D deficiency associated with higher sepsis mortality and longer hospital stay

22nd July 2022

Severe vitamin D deficiency at emergency department admission for severe sepsis is linked to a higher mortality and longer hospital stay

Patients with severe vitamin D deficiency upon admission to an emergency department (ED) with severe sepsis have a higher level of mortality and a longer hospital stay according to the findings of a single centre, prospective study by researchers from Belgium and Italy.

Alterations in the levels of vitamin D have been associated with a higher susceptibility to immune-mediated disorders and inflammatory diseases. However, whilst research suggests that vitamin D has a potential role in the optimal functioning of the immune system, whether correction of vitamin D depletion, particularly among critical care patients, serves an important adjunctive role in either the prevention or treatment of infection is uncertain. In fact, if anything, the available evidence would indicate that vitamin D administration does not improve clinical outcomes among critically ill patients. Nevertheless, an important consideration is how vitamin D levels were normally measured once a patient had been admitted to hospital or after the provision of various treatments and this could have affected measured levels of the vitamin. As a result, in the present study, the researchers sought to determine whether severe vitamin D upon admission to an ED in those with severe sepsis was associated with a higher risk of mortality and a longer hospital stay.

The research team recruited adult patients admitted to the ED with a suspicion of severe sepsis and measured vitamin D levels alongside routine blood samples. Using the patient’s medical records, the team also collected demographic and clinical factors such as the age-adjusted Charleson Comorbidity Index (ACCI), Acute Physiological and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Severe vitamin D deficiency was defined as a level < 12 ng/ml and moderate severity as between 12 and 20 ng/ml. The primary outcome was set at 90-day all-cause mortality and for the secondary outcomes, the team selected a number of measures including the length of hospital stay.

Severe vitamin D levels and mortality

A total of 164 patients with a median age of 66.7 years (35% female) were included in the final analysis. Among the cohort, 46.3% of patients had vitamin D levels below 12 ng/ml and 121 of the cohort were admitted to intensive care. The 90-day all-cause mortality occurred in 26.4% of the entire cohort and the median hospital length of stay was 14 days.

Among those with vitamin D levels below 12 ng/ml, 32.9% of patients died compared to 20.5% in the non-severe deficiency group (p = 0.07) and in multivariable analysis after adjustment for sepsis severity and co-morbidities, this was found to be independently associated with 90-day mortality (odds ratio, OR = 2.69, 95% CI 1.03 – 7, p = 0.043). Using Cox analysis again adjusted for confounders, severe vitamin D deficiency was also associated with a lower chance of hospital discharge (hazard ratio, HR = 0.66, 95% CI 0.44 – 0.98, p = 0.043).

As with the overall cohort, among patients admitted to ICU, those with severe vitamin D deficiency had a higher risk of 90-day mortality (HR = 3.06, 95% CI 1.05 – 8.94, p = 0.04) and a lower chance of discharge (HR = 0.51).

Citation
Malinverni S et al. Severe vitamin D deficiency in patients admitted to the emergency department with severe sepsis is associated with an increased 90-day mortality Emerg Med J 2022

Post-MI mortality risk reduced in overweight/obese but higher for underweight individuals

6th June 2022

Post-MI mortality is significantly lower among those with an above normal BMI yet much higher for individuals when their BMI is below normal

The post-myocardial infarction (post-MI) mortality risk has been found to be significantly lower among those who are classed as overweight or obese yet much higher for those with a body mass index (BMI) below the ideal range. This was the conclusion of a systematic review and meta-analysis by an international team led by researchers from Aberdeen University, Scotland, UK.

Body mass index (BMI) is a measure of nutritional status in adults and defined as a person’s weight in kilograms divided by the square of the person’s height in metres (kg/m2). Based on the BMI, individuals are deemed to be of normal weight when their BMI is being 18.5 and 24.9. According to the World Health Organization, individuals with a BMI > 25 are classed as overweight, and obese when their BMI is equal to or > 30). According to the American Heart Association, the presence of obesity leads to the development of cardiovascular disease and mortality, independently of other cardiovascular risk factors. However, there is increasing evidence that patients with an elevated BMI may have better outcomes if they develop cardiovascular or renal disease, which is referred to as the “obesity paradox”. Despite this, meta-analyses support a J-shaped relationship between mortality and BMI in patients with coronary artery disease, i.e., the risk is highest for underweight and overweight individuals and lowest for those with a normal BMI.

Nevertheless, whether this same J-shaped relationship holds for post-MI mortality is unknown and was subject of the present meta-analysis. The researchers looked for studies in adults with a previous myocardial infarction where the BMI had been measured and which reported on outcomes such as all-cause mortality, recurrence of an adverse cardiovascular event or hospital re-admission. Hazard ratios (HRs) were used to assess the risk of mortality and the normal BMI (18.5 – 24.9) was used as the reference range for comparative purposes.

Post-MI mortality and BMI

A total of 27 articles with 308,430 participants and with follow-up periods ranging from 6 months to 17 years were included in the analysis.

Among individuals who were classed as overweight (BMI 25 – 29.9) compared to those of normal BMI and based on 8 studies, there as a 15% lower risk of post-MI mortality (HR = 0.85, 95% CI 0.76 – 0.94, p = 0.002). In 14 studies that reported on odds ratios (ORs) rather than hazard ratios, there was also a reduced mortality risk (OR = 0.72, 95% CI 0.64 – 0.81, p < 0.0001).

Among obese patients (BMI > 30) the HR was 0.86 (95% CI 0.81 – 0.91, p < 0.0001) and for morbidly obese patients, although the HR was reduced, it was not statistically significant (HR = 0.89, 95% CI 0.78 – 1.01, p = 0.08).

In contrast, among those with a BMI < 18.5, there was a 42% higher risk of post-MI mortality (HR = 1.42, 95% CI 1.25 – 1.62, p < 0.0001) and again, where studies reported odds ratios, this was also significantly increased (OR = 2.48, 95% CI 1.77 – 3.47, p < 0.0001).

There were no significant effects when comparing the risk of hospital re-admission for those who were overweight, obese and underweight.

The authors concluded that individuals who have a BMI less than the normal range are at a significantly higher risk of post-MI mortality. They called for future studies to examine the prognostic utility of other markers of nutritional status in MI to better identify those at a higher risk of poor clinical outcomes.

Citation
De Paola L et al. Body Mass Index and Mortality, Recurrence and Readmission after Myocardial Infarction: Systematic Review and Meta-Analysis J Clin Med 2022

COVID-19 vaccinated cancer patients at increased risk of breakthrough infections

13th April 2022

COVID-19 vaccinated cancer patients have a greater risk of breakthrough infections leading to higher rates of hospitalisation and mortality

COVID-19 vaccinated cancer patients have been found to be at a higher risk of breakthrough infections and which are associated with a substantial risk of hospitalisation and mortality. This was the conclusion of a retrospective cohort study of electronic health records by a team from the Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Ohio, US.

Patients with cancer have been found to be at a significantly increased risk for COVID-19 infection and worse outcomes though fortunately, COVID-19 vaccination has been shown to be associated with lower infection rates in cancer patients. However, despite vaccination, the occurrence of breakthrough infections has also been reported and this appears to be correlated with neutralising antibody titers during the peri-infection period. While COVID-19 vaccinated cancer patients are also potentially likely to experience breakthrough infections, there is a lack of data on the extent to which such breakthrough infections occur among those with cancer and how, or if, this might be influenced by the different cancer sites.

For the present study, the US team turned to the TriNetX database which contains de-identified information on 90 million patients in the US. The team looked for vaccinated patients with one of 12 different cancers including pancreatic, liver, lung, colorectal, skin and thyroid and compared the level of breakthrough infections with a group of vaccinated, patients without any of the specified cancers. Data on age, sex, race and co-morbidities were collected for all patients and adjusted for in the analysis. The researchers examined the monthly incidence of breakthrough infections between December 2020 and November 2021 as well as the risk of hospitalisation and death among those infected.

COVID-19 vaccinated cancer patients and breakthrough infections

A total of 45,253 vaccinated cancer patients with a mean age of 68.7 years (53.5% female) were included in the analysis and matched with 591,212 vaccinated, non-cancer patients.

The cumulative risk of a breakthrough infection during the period of study among vaccinated COVID-19 cancer patients, was 13.6% which was higher than vaccinated, non-cancer patients, (Hazard ratio, HR = 1.24, 95% CI 1.19 – 1.29). Among the different cancer sites, the highest risk was for patients with pancreatic cancer (24.7%), followed by liver (22.8%), lung (20.4%) and colorectal (17.5%). The only cancer not associated with a significant increased risk for a breakthrough infection was thyroid (HR = 1.07, 95% CI 0.88 – 1.30) although the increased risk among patients with skin cancer was of borderline significance (HR = 1.17, 95% CI 0.99 – 1.38).

The risk of hospitalisation among cancer patients with breakthrough infections was much higher than matched, non-cancer patients (31.6% vs 3.9%, HR = 13.48). In addition, mortality risks were also significantly elevated (HR = 6.76, 95% CI 4.97 – 9.20).

The authors concluded that their results emphasised the need for those with cancer to maintain mitigation practices, especially given the emergence of COVID-19 variants for which vaccination might not provide full protection.

Citation
Wang W et al. Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Mortality in Vaccinated Patients With Cancer in the US Between December 2020 and November 2021 JAMA Oncol 2022

Large study confirms less severe outcomes after infection with Omicron compared with Delta variant

29th March 2022

A large UK comparative analysis has found that infection with the Omicron COVID-19 variant leads to less severe outcomes than with delta

Individuals who become infected with the Omicron COVID-19 variant experience less severe outcomes such as hospitalisation and death compared to those with the Delta variant according to the results of a large study by a multi-disciplinary group of UK researchers.

The Omicron COVID-19 variant has produced a surge of infections and been found to be associated with high transmission among household contacts, particularly among those who lived with index patients who were not vaccinated or who did not take measures to reduce the risk of transmission to household contacts. Nevertheless, despite a higher level of transmissibility, studies have also suggested that the Omicron variant is associated with substantial severity of illness in comparison to the Delta variant.

With an increasing number of individuals now fully vaccinated against COVID-19, the purpose of the present study was to offer a more detailed understanding of the overall impact of both less severe outcomes and greater immunity on rates of hospitalisation and mortality during the Omicron wave. The UK team obtained individual-level data on confirmed cases of COVID-19 infection in England between November 2021 and 9 January 2022 and linked these to vaccination status, hospital attendance and admission as well as deaths. During the period of study genomic sequencing was performed for some of the infections which enabled the team to distinguish between the two variants. For the study, a hospital admission was defined as a stay of at least one or more days. The analysis was stratified by age, vaccination status and adjusted for sex, deprivation index and evidence of prior infection.

Omicron caused less severe outcomes

During the period of study there were 4,135,347 confirmed cases of COVID-19, of which 1,526,702 (37%) had information on the infecting variant and consisted of 448,843 Delta and 1,067,859 Omicron cases.

The adjusted hazard ratio (HR) for attendance at hospital, but not necessarily admission, was lower for Omicron than Delta (HR = 0.56, 95% CI 0.54 – 0.58). In addition, compared to Delta, the risk of hospital admission among those infected with Omicron was 59% lower (HR = 0.41, 95% CI 0.39 – 0.43) and the risk of death within 28 days was 69% lower (HR = 0.31, 95% CI 0.26 – 0.37).

When stratified by age, there was no difference between the two variants among those 10 years of age and younger (HR = 1.10, 95% CI 0.85 – 1.42). However, there was a significant difference and reduction among those at least 80 years of age (HR = 0.47, 95% CI 0.40 – 0.56).

For both of the variants, prior infection offered protected against death in those who were vaccinated (HR = 0.47) and unvaccinated (HR = 0.18). Interestingly, among those who were vaccinated, prior infection appeared to offer no additional protection against infection (HR = 0.96, 95% CI 0.88 – 1.04), which was in contrast to those who were unvaccinated but had a previous infection (HR = 0.55, 95% CI 0.48 – 0.63).

The authors concluded that the less severe outcomes observed for Omicron were largely driven by a less severe variant and increased immunity due to vaccination.

Citation
Nyberg T et al. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study Lancet 2022

Sodium content in soluble paracetamol linked to higher CVD and mortality risk

10th March 2022

Greater sodium intake from soluble paracetamol is associated with a higher CVD and mortality risk in patients with and without hypertension

A higher sodium intake from the use of soluble paracetamol tablets has been found to increase the risk of both cardiovascular disease (CVD) and mortality in patients, irrespective of their hypertensive status. This was the conclusion of a study by researchers from the Department of Orthopaedics, Xiangya Hospital, Changsha, China.

It has been known for some time that a higher sodium intake increases blood pressure and is therefore a risk factor for cardiovascular disease. Furthermore, an increased intake of the mineral has also been linked to an additional 1.65 million deaths from cardiovascular causes above a reference level intake of 2.0 g per day. In addition, studies suggest that in comparison to a moderate intake of sodium, higher intakes are associated with an increased risk of cardiovascular events and death among those with hypertensive but not form normotensive patients.

While lowering intake of sodium is known to be associated with a reduced risk of stroke and fatal coronary heart disease in adults, it would be unethical to examine the impact of a greater intake on CVD and mortality risk, given the benefits of reducing intake. While dietary sodium is a major source of intake, sodium is also contained within several medicines, in particular, soluble paracetamol. For the present study, the Chinese team compared the risks of incident CVD and all-cause mortality associated with the intake of sodium-containing soluble paracetamol (acetaminophen) compared to intake of non-sodium containing formulations according to patient’s hypertension status.

The team turned to the Health Improvement Network which is an electronic medical record database in the UK containing anonymised data for approximately 17 million patients as their source of information. They extracted data for two separate cohorts. The first included patients aged 60 – 90 years of age and with a diagnosis of hypertension and prescribed either a sodium and non-containing paracetamol formulation. The second cohort was similar although this time included patients without a diagnosis of hypertension. Socio-demographic data including gender, age, body mass index and various lifestyle factors were recorded and used as covariates in their analysis. The primary outcomes of interest were incident CVD which included myocardial infarction, stroke and heart failure, and all-cause mortality.

Sodium intake and CVD/mortality outcomes

For the first cohort, a total of 151,398 individuals with a mean age of 78.3 years (65.8% female) and a history of hypertension were included and of whom, 4532 were given a sodium-containing paracetamol. These were matched with a total of 147,299 without hypertension and a mean age of 71.4 (63.3% female), of whom 5,351 were given a sodium-containing paracetamol formulation.

Among those with hypertension, there were 122 cases of CVD among those given the mineral and 3051 cases among the non-sodium group over a median follow-up period of 0.89 and 0,93 years respectively. This gave a 59% higher risk of incident CVD among those taking a sodium-containing paracetamol formulation (Hazard ratio, HR = 1.59, 95% CI 1.32 – 1.92). Furthermore, the risk of all-cause mortality was more than double (HR = 2.05, 95% CI 1.92 – 2.19).

Among those given a sodium-containing paracetamol formulation but without hypertension, there was a 45% increased risk of CVD (HR = 1.45, 95% CI 1.18 – 1.79) and a 87% increased mortality risk (HR = 1.87, 95% CI 1.74 – 2.00).

Commenting on these results, the authors noted that sodium-containing drugs are an important but often overlooked source of the mineral. They concluded that individuals should avoid unnecessary excessive sodium intake through sodium-containing paracetamol use.

Citation
Zeng C et al. Sodium-containing acetaminophen and cardiovascular outcomes in individuals with and without hypertension Eur Heart J 2022

Re-hospitalisation and mortality risk higher for COVID-19 patients than the general population

14th February 2022

Re-hospitalisation and mortality risks are higher than the general population for patients initially hospitalised with COVID-19

Rates of re-hospitalisation and mortality among people who were originally admitted to hospital with an acute COVID-19 infection, appear to be much higher than those hospitalised with other conditions. This was the key finding from an analysis of information in the OPENSAFELY database by researchers at the Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

During the early stages of the COVID-19 pandemic, although many patients were initially managed in an outpatient settings, one study found that 15% of cases required hospitalisation and 4% died within a month of first symptoms. The introduction of COVID-19 vaccines have been effective at preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations. Nevertheless, there is little currently known about the subsequent outcomes for those patients who were initially hospitalised because of COVID-19, although where such data does exist, it appears that patients are still at risk of future adverse outcomes. For example, in one US study it was found that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Similarly, a UK-based study concluded that individuals discharged from hospital after COVID-19 had increased rates of multi-organ dysfunction compared with the expected risk in the general population.

For the present study, the UK team decided to examine the incidence of subsequent re-hospitalisation and death in those initially admitted to hospital with COVID-19 in comparison to both the general population and those who were hospitalised prior to the pandemic, with influenza. They used the OPENSAFELY platform which provides information from primary care practices and linked patient information with other databases providing data on hospitalisations and mortality. Their main outcomes of interest were re-hospitalisation or death and all-cause mortality. The team used used regression models which were adjusted for a number of covariates such as age, sex, ethnicity, obesity and other co-morbidities.

Re-hospitalisation and mortality after acute COVID-19

The analysis included 24,673 individuals discharged from hospital after a COVID-19 hospitalisation and who were matched with 123,362 controls and 16,058 patients who had been hospitalised and discharged due to influenza. COVID-19 patients had a median age of 66 years (55.7% male) which was slightly younger than the median age of those hospitalised due to influenza (69 years).

The overall risk of re-hospitalisation was higher in the discharged COVID-19 group compared to the general population (adjusted hazard ratio, aHR = 2.22, 95% CI 2.14 – 2.30, p < 0.001). However, the risk of re-hospitalisation was lower than the influenza group (aHR = 0.95, 95% CI 0.91 – 0.98, p = 0.004).

All-cause mortality was higher in the COVID-19 discharged group than in the general population (aHR = 4.82, 95% CI 4.48 – 5.19, p < 0.001) and for the influenza group (aHR = 1.74, 95% 1.61 – 1.88, p < 0.001).

When examining the reported cause of death, 24.7% of deaths had COVID-19 listed as the cause although in comparison, less than 5 deaths were reportedly due to influenza.

The authors concluded that among patients who survived hospitalisation after an acute infection with COVID-19, there was a substantially higher risk of subsequent re-hospitalisation and death over the next 10 months. They suggested that these findings highlighted a need for services to support and closely monitor people following discharge from hospital.

Citation
Bhaskaran K et al. Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care, secondary care, and death registration data in the OpenSAFELY platform. PLos Med 2022