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Higher body fat levels in men linked to increased risk of prostate cancer death

12th May 2022

Higher body fat levels in men leads to an increased risk of prostate cancer death according to a meta-analysis of prospective studies

A higher body fat level in men is associated with an elevated risk of prostate cancer death according to a meta-analysis of prospective studies by researchers from the Nuffield Department of Population Health, Cancer Epidemiology Unit, University of Oxford, Oxford, UK.

Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide and in 2020 there were more than 1.4 million new cases of prostate cancer. Prior evidence indicates that there is a positive association between height and the risk of prostate cancer, with taller men being at a greater risk but also that those with greater adiposity, have an elevated risk of high-grade prostate cancer and prostate cancer death. Moreover, other work suggests that a higher body fat level, based on central adiposity is a more relevant factor and that a higher waist circumference was an important risk factor for prostate cancer.

For the present study, the Oxford team use data from the UK Biobank and focused on men who had originally undergone anthropometric measurements (e.g., height, weight, waist and hip circumference). A subgroup of these men also underwent abdominal MRI and a dual-energy X-ray absorptiometry (DXA) scan and for whom body mass index (BMI), waist and hip circumferences were re-assessed. The primary outcome of interest was prostate cancer as the underlying cause of death. In addition, the researchers combined their Biobank data with other published prospective studies to undertake a dose response meta-analysis.

Higher body fat levels and prostate cancer death

Among a cohort of 21,8237 men with a mean age at recruitment of 56.5 years, over a follow-up period of 11.6 years, 661 men (mean age = 63.1 years), died of prostate cancer.

In a multivariable-adjusted model, there was no statistically significant association of BMI, body fat percentage and waist circumference and prostate cancer mortality. However, for the waist to hip ratio (WHR), this association was significant per 0.05 unit increase (hazard ratio, HR = 1.07, 95% CI 1.01 – 1.14, P for trend = 0.028) when comparing the highest to lowest WHR quartiles.

In the meta-analysis, the hazard ratio was 1.10 (95% CI 1.07 – 1.12) for every 5kg/m2 increase in BMI, 1.03 for every 5% increase in body fat percentage, and 1.06 for every 0.05 increase in WHR.

Using the estimate for the effect of BMI from the meta-analysis, the authors estimated that as approximately 11,900 men died from prostate cancer each year (averaged between 2016 – 2018) and if their estimate was accurate, a reduction in mean BMI of 5kg/m2 would potentially lead to 1309 fewer prostate cancer deaths every year in the UK.

They concluded that men with higher body fat (both total and central) were at a higher risk of death from prostate cancer and that these findings provided a reason for men to maintain a healthy weight.

Citation
Perez‐Cornago A et al. Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies BMC Med 2022


Adding coronary artery calcium scores to CVD risk assessment provides no clinical benefit

6th May 2022

Addition of coronary artery calcium scores to a patient’s cardiovascular risk assessment does not appear to provide any clinical benefit

Adding coronary artery calcium scores (CACS) to further assess an individual’s cardiovascular risk assessment does not appear to be associated with any clinical benefit. This was the main finding of a systematic review and meta-analysis by a team from the School of Public Health, University of Sydney, Sydney, Australia.

Cardiovascular risk assessment is a critical step in the current approach to primary prevention of heart disease and is calculated using tools such as QRISK. Cardiac computed tomography (CT) imaging is an important tool for cardiovascular risk assessment in observational prospective studies and which provides a measure of subclinical disease such as coronary artery calcium. Moreover, the use of CACS has been shown to be an independent predictor of incident coronary heart disease among those deemed to be at intermediate-risk based on their Framingham risk score. The use of CACS screening has been found to improve medication adherence and provide superior coronary artery disease risk factor control without increasing downstream medical testing. By contrast, however, a study in post-menopausal women concluded that there was no independent benefit of coronary CT imaging in a low-to-moderate risk group.

With some uncertainty over whether addition of CACS derived from CT imaging provides an incremental benefit beyond that obtained from traditional risk assessment methods, in the current study, the Australian team undertook a systematic review and meta-analysis of available studies. They included studies in patients without existing cardiovascular disease, where at least one recognised risk calculator and a CACS had been used. The primary outcome as the change in C statistic for a model which contained the CACS compared to the base model without the CACS.

Coronary artery calcium scores and improvement in CVD risk prediction

A total of 6 studies with 17,961 individuals and 1043 cardiovascular events were included in the analysis. The studies varied in sample size from 470 to 5185 and mean ages ranged from 50 to 75.1 years (38.4 to 59.4% female).

The C statistic for cardiovascular disease (CVD) risk models but without CACS ranged from 0.693 to 0.80. Inclusion of CACS improved the pooled C statistic by 0.036.

When CACS was added, among participants whose risk was reclassified from low to intermediate or high risk, 85.5% to 96.4% did not experience an event during follow-up (ranging from 5.1 to 10 years). Among those who were reclassified from high risk to low risk by CACS, a similarly high proportion, 91.4% to 99.2% did not have a CVD event during follow-up.

The authors suggested that while CACS did appear to provide modest further discriminatory power to traditional risk factor assessments, this additional gain needed to be balanced against the higher costs and radiation risks. They concluded that while there were gains from inclusion of CACS, which patients might benefit remains to be determined and that there is no evidence to suggest that use of CACS offers a clinical benefit.

Citation
Bell KJL et al. Evaluation of the Incremental Value of a Coronary Artery Calcium Score Beyond Traditional Cardiovascular Risk Assessment: A Systematic Review and Meta-analysis JAMA Intern Med 2022

First-pass success rate comparable for inclined vs supine positioning during endotracheal intubation

27th April 2022

A review suggests that the first-pass success rate is equivalent when patients are either inclined or supine during endotracheal intubation

The first-pass success rate is no better during endotracheal intubation whether patients are in the inclined or supine position. This was the conclusion of a systematic review by a team from the Department of Emergency Medicine, Indiana University School of Medicine, Indiana, USA.

Tracheal intubation is a procedure that is commonly performed outside of an operating theatre and has been found to be associated with higher risk than intubation in theatre. Performance of endotracheal intubation in the sitting or inclined position has been described as a useful technique for rapid airway control in the patient for whom maintenance of the upright posture is desirable. Although the use of the inclined position was described more than 30 years ago, research in 2016 demonstrated that placing patients in a back-up head-elevated position, compared with supine position, during emergency tracheal intubation was associated with a reduced odds of airway-related complications. However, not all studies have been positive with one 2017 randomised trial concluding that the ramped (inclined) position did not improve oxygenation during endotracheal intubation of critically ill adults compared with the sniffing (supine) position. A 2021 systematic review on the comparative merits of the inclined vs supine condition for tracheal intubation which set the primary outcomes as a successful first attempt at intubation, the number of tracheal intubation attempts and adverse events, found favourable aspects of the inclined compared to the supine position. However, the review did not include any emergency department studies and for the present review, the US team sought to examine the association between the inclined and supine positioning on first-pass success across a range of clinical settings.

The team searched for trials comparing both positions and used the first-pass success, which is a widely reported metric, as the primary outcome of interest. Several secondary outcomes including hypoxia, hypotension, mortality and time to intubation were also examined.

First-pass success and endotracheal intubation

A total of 10 studies with 18,371 intubations were included in the analysis and studies were randomised, prospective/observational and retrospective in nature though only two studies were undertaken in an emergency department.

The quality of the evidence with respect to the primary outcome of interest, first-pass success, was rated as low. Nevertheless, when comparing the two positions, there was no difference in the primary outcome (relative risk, RR = 1.02, 95% CI 0.98 – 1.05). In addition, there were also no significant differences for the secondary outcomes such as hypoxaemia (RR = 0.87, 95% CI 0.48 – 1.51), hypotension (RR = 1.33, 95% CI 0.77 – 2.29) and mortality (RR = 0.81, 95% CI 0.62 – 1.04).

The authors concluded that their review had demonstrated no evidence of either benefits or harm associated with the inclined versus supine positioning during an endotracheal intubation in any setting. However, they recognised that the overall quality of the evidence was rated as low or very low for most of the outcomes.

Citation
Turner JS et al. Effect of inclined positioning on first-pass success during endotracheal intubation: a systematic review and meta-analysis Emerg Med J 2022

Depression risk greatly reduced even by low levels of physical activity

21st April 2022

The depression risk can be greatly reduced by undertaking low levels of physical activity according to a recent systematic review

The risk of depression can be greatly reduced even by undertaking lower amounts of the recommended levels of physical activity according to the results of a meta-analysis by researchers from the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

Depression is a common, global mental disorder that is believed to affect 5% of the population. Moreover, a 2015 meta-analysis estimated that every year, 14.3% of global deaths, approximately 8 million deaths, can be linked to mental disorders. With such a high prevalence and associated mortality, much needs to be done to try and prevent or reduce depression risk. One possible mitigating factor is physical activity and according to one systematic review, promoting physical activity may serve as a valuable mental health promotion strategy in reducing the risk of developing depression. In fact, a 2018 meta-analysis of prospective cohort studies suggested that the available evidence supports the idea that physical activity can confer protection against the emergence of depression regardless of age and geographical region. With a good deal of evidence indicating a protective effect from physical activity, what remains uncertain is the strength or shape of the association between physical activity and depression.

For the present analysis, the UK team looked for trials that included any dimension of physical activity at three or more exposure levels, with at least 3,000 participants and with a follow-up period of not less than 3 years. Levels of physical activity were measured as marginal metabolic equivalents task hours per week (mMet-h/wk), where 1 Met represented the resting metabolic rate and 8.8 mMet-h/week was equivalent to the recommended weekly amount of physical activity. The outcome of interest was depression, major depressive disorder and elevated depression symptoms.

Depression risk and physical activity levels

The literature review identified 15 eligible publications including 191,130 participants (64% women) contributing 28,806 incident depression events and 2,110,588 person-years.

The results suggested an inverse and curvilinear dose-response between physical activity and depression, such that relative to adults who did not report undertaking any physical activity, those doing at least half of the recommended activity (4.4 mMet-hrs/week), had an 18% lower risk of depression (relative risk, RR = 0.82, 95% CI 0.77 – 0.87). Among those achieving the recommended amounts of activity (8.8 mMet-hrs/week), there was a 25% reduced risk of depression (RR = 0.75, 95% CI 0.68 – 0.82) and this reduction was the same for major depression and slightly lower for elevated depressive symptoms (RR = 0.73). However, interestingly, there was little apparent benefit derived from increasing activity to 17.5 mMet-hrs/week (RR = 0.72, 95% CI 0.64 – 0.81), for each of the three outcome measures.

Using potential impact fraction (PIF) analysis, the authors calculated that around 11.5% of incident depression could have been prevented in adults who achieved at least 8.8 mMet-hrs/week of physical activity.

Translating their findings into practical advice, the authors stated that accumulating an activity equivalent to 2.5 hours/week of brisk walking was associated with a 25% lower risk of depression and that achieving half of this level, reduced the risk by 18% compared with those who undertook no physical activity.

They concluded that substantial mental health benefits accrue from the achievement of physical activity levels even below those currently recommended.

Citation
Pearce M et al. Association Between Physical Activity and Risk of Depression: A Systematic Review and Meta-analysis JAMA Psychiatry 2022

Meta-analysis finds sodium-glucose co-transporter-2 inhibitors reduce adverse CV outcomes in acute decompensated heart failure

20th April 2022

Sodium-glucose co-transporter-2 inhibitors reduce adverse cardiovascular outcomes in patients with acute decompensated heart failure

The use of sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) in patients with acute, decompensated heart failure is associated with a reduction in adverse cardiovascular outcomes compared with placebo. However, these improvements do not translate into a significant reduction in all-cause mortality, as concluded by a meta-analysis of trials by researchers from the University of Thessaloniki, General Hospital “Hippokration,” Thessaloniki, Greece.

Heart failure (HF) is a complex clinical syndrome characterised by the reduced ability of the heart to pump and/or fill with blood failure. Heart failure is a common problem and globally, the age-standardised prevalence of HF in 2017 was 831.0 per 100,000 people. Moreover, the prognosis of those with more severe HF is poor, with one study finding that among patients hospitalised with HF, the 1-year mortality rate was only 40%.

The sodium-glucose co-transporter 2 receptors are primarily located in the proximal convoluted tubule of the nephron and are responsible for almost 90% to 95% of tubular reabsorption of glucose in the nephron. The SGLT-2Is are a class of drugs originally designed for the management of type 2 diabetes (by preventing glucose re-uptake) although research over the last decade has found that the drugs also have beneficial effects in heart failure. As a result, some members of this class such as empagliflozin, are also licensed in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction.

However, whether these drugs are also effective in patients with acute decompensated HF remains to be determined and was the subject of the meta-analysis by the Greek researchers. The team searched for randomised, controlled trials that enrolled adult patients, irrespective or whether they had diabetes, and who were assigned to a SGLT-2I or placebo or an active comparator. They set the primary safety endpoint as the effect of SGLT-2I on recurrent worsening heart failure (WHF). Several secondary endpoints were used: all-cause mortality; a composite of cardiovascular death or recurrent hospitalisation for HF decompensation and finally, the observed diuretic response. This latter endpoint was defined as the weight change per standard loop diuretic dose. The effects of treatment were assessed using risk ratios (RR).

Sodium-glucose co-transporter-2 inhibitors and heart failure outcomes

The researchers only identified three relevant clinical trials including 1,831 patients.

Compared with placebo, the use of SGLT-2Is produced a signification reduction in the risk of WHF (RR = 0.66, 95% CI 0.58 – 0.76, p < 0.00001). Similarly, there was also a significant 30% reduced risk of the composite endpoint of cardiovascular death or re-hospitalisation for decompensated HF (RR = 0.70, 95% CI 0.62 – 0.78, p < 0.00001). Interestingly, despite these benefits, there was no significant effect on all-cause mortality (RR = 0.72, 95% CI 0.48 – 1.09, p = 0.12) and a non-significant effect on diuretic response, mean difference = – 1.15 (95% CI -3.18 to 0.17, p = 0.26).

Based on their findings, the authors concluded that their data indicated how the use of SGLT-2I drugs significantly reduced recurrent worsening of HF but called for further trials to clarify whether these drugs should become part of the treatment algorithm for HF patients.

Citation
Patoulias D et al. Meta-Analysis Evaluating the Efficacy of Sodium-Glucose Co-Transporter-2 Inhibitors in Patients With Acute or Recently Decompensated Heart Failure Am J Cardiol 2022

Study shows immune checkpoint inhibitors combined with radiotherapy offers no survival benefit in melanoma

8th April 2022

Immune checkpoint inhibitors and radiotherapy offer no survival benefit in melanoma, although 12-month progression-free survival is improved, according to a study

A meta-analysis by researchers from Beijing Tongren Hospital, Capital Medical University, Beijing, China, has concluded that adding radiotherapy to immune checkpoint inhibitors (ICIs)for the treatment of patients with melanoma offers no overall survival benefit despite a significant improvement in 12-month progression-free survival.

According to the World Cancer Research Fund, melanoma is the 19th most commonly occurring cancer in men and women, with nearly 300,000 new cases reported in 2018. Among patients whose melanoma has undergone metastases, ICIs, monoclonal antibodies which target the programmed death cell protein 1 (PD-1), the programmed death-ligand 1 (PD-L1), or the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), represent the standard of care. Nevertheless, while effective, when used as mono-therapy, ICIs produce an overall response rate ranging from 0% to 17%, though these figures increase to more than 33.3% when the agents are combined.

Radiotherapy is routinely used in treatment of solid cancers, such as hepatocellular carcinoma (HCC) and several preclinical and clinical studies have explored the efficacy of combining radiotherapy and ICIs in HCC and with promising outcomes. Moreover, a meta-analysis of 11 studies found that combining ICIs with radiotherapy showed better local efficacy than ICI mono-therapy for treating melanoma brain metastasis.

Despite this, few studies have systematically examined the combined effect of ICIs and radiotherapy in the treatment of patients with melanoma. For the present study, the Chinese team set out to summarise the efficacy of radiotherapy in combination with ICIs in the treatment of non-brain metastatic melanoma. They included all available trials such as single-arm and control studies in which the endpoints of overall response rate (ORR), overall survival (OS) or progression-free survival (PFS) were reported. The team used regression analysis and presented their results using odds ratios.

Immune checkpoint inhibitors and radiotherapy outcomes

After an extensive literature search, 9 articles (7 retrospective studies and 2 prospective cohort trials) involving 624 patients were identified and included in the analysis.

Combing radiotherapy with ICIs led to a higher ORR compared with ICIs alone (35% vs 20.4%, p = 0.004) However, in terms of OS, the 12-month odds ratio (OR) comparing the combination to ICI treatment alone was 1.83 (95% CI 0.32 – 5.52, p = 0.69) and hence not significantly different.

While there was no significant difference between the two treatment options in PFS at 6-months (OR = 0.53, 95% CI 0.26 – 1.08, p = 0.08), this difference became significant at 12-months (OR = 0.48, 95% CI 0.29 – 0.80, p = 0.005).

Commenting on these findings, the authors highlighted that with most studies being retrospective in nature and no randomised trials, there was a need for prospective trials to further explore the efficacy of combining radiotherapy with ICIs in melanoma.

They concluded that while, at present, there was no evidence of a survival benefit by combining the two therapies, an improvement in PFS was evident but further high quality trials were required to confirm these findings.

Citation
Yin G et al. Efficacy of radiotherapy combined with immune checkpoint inhibitors in patients with melanoma: a systemic review and meta-analysis Melanoma Res 2022

Music interventions associated with improvement in mental and physical health-related QOL

31st March 2022

The use of music interventions appear to be associated with clinically meaningful improvements in mental and a smaller improvement in physical health-related quality of life. However, the specific type of music intervention providing the greatest benefit remains unclear. This was the conclusion from a meta-analysis of studies by researchers from the Institute of Music Physiology and Musicians’ Medicine, Hannover University of Music, Hannover, Germany.

The use of music interventions (MIs) such as listening to music, playing an instrument or singing, has been shown to positively impact on the global and social functioning of patients with mental health conditions such as schizophrenia. Furthermore, there is also reliable evidence for the positive effects of music and singing on wellbeing (related to the positive aspects of a person’s life) in adults without underlying mental health problems. Other evidence from an umbrella review of performing arts as a health resource, concluded that positive health effects were associated with as little as 30 to 60 minutes of performing arts participation.

The CDC in the US defines health-related quality of life (HRQOL) as an individual’s or a group’s perceived physical and mental health over time. HRQOL can be assessed using dedicated questionnaires, including the 36-item Health Survey Short Form (SF-36) and related, reduced 12-item Health Survey Short Form (SF-12). Moreover, both the SF-36 and 12 have been used in studies of music interventions.

Although music interventions appear to give rise to improvements in both HRQOL and well-being, what remains unclear is the associations between different types of MIs and changes in HRQOL as measured using both the SF-36 and SF-12. This was the purpose of the current study and the German team included randomised and non-randomised trials that investigated music making (singing, listening, playing music) interventions and which reported changes in SF-36 or SF-12, before and after the intervention. The researchers focused on both the mental component summary (MCS) and the physical component summary (PCS) of the SF-36 or SF-12 since higher scores in each of these domains were indicative of better mental and physical HRQOL. The threshold mean difference in MCS scores was set as a mean difference of 3 or more.

Music interventions and MCS and PCS scores

The literature search identified 26 eligible studies with 779 participants (mean age = 60 years) and which comprised listening to music, music therapy, singing with one study exploring the effect of gospel music.

Overall, a music intervention was associated with a significant decrease in both MCS (total mean difference, TMD = 2.95, p < 0.01) and PCS scores (TMD = 1.09, p = 0.02) compared to pre-intervention values.

In subgroup analysis, in which MIs were added to usual treatment, there was a significant increase in MCS scores vs usual treatment alone (TMD = 3.72, 95% CI 0.40 – 7.05) but not for PCS. However, it was not possible to identify any important differences based on the type of musical intervention.

The authors concluded that while MIs led to a significant increase in mental HRQOL, the changes in PCS were equivocal. They added that given the variation in the effect of the different interventions such as singing, listening to music etc, it was not possible to provide any firm recommendations about the optimal intervention or dosage for use in specific clinical scenarios.

Citation
McCrary JM et al. Association of Music Interventions With Health-Related Quality of Life: A Systematic Review and Meta-analysis JAMA Netw Open 2022


Statin therapy associated with only modest absolute risk reductions for cardiovascular outcomes

24th March 2022

Statin therapy has been found to be associated with only a modest absolute risk reduction in adverse cardiovascular disease outcomes

Statin therapy is associated with only a modest absolute risk reduction in cardiovascular disease outcomes including all-cause mortality and myocardial infarction (MI). This was the important main finding from a meta-analysis of randomised trials by researchers from the HRB Centre for Primary Care Research, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

It widely thought that the key initiating event in atherogenesis is the retention of low-density lipoprotein (LDL) cholesterol and other cholesterol-rich lipoproteins within the arterial wall. As a result, a great deal of effect has been directed at reducing LDL cholesterol levels so that the treatment with a statin drug has become a well-recognised approach for lowering LDL cholesterol. While there are clearly benefits from the use of statins, in much of the published work, authors report relative rather than absolute risk reductions. This represents an important weakness for the interpretation of the data since readers tend to overestimate the effect of an intervention when the results are expressed in relative terms. In contrast, the absolute risk gives a better representation of the actual situation and also from the patient’s point of view, absolute risks often give more relevant information.

For the present meta-analysis, the Irish team analysed both the relative and absolute risks associated with the use of statin therapy for outcomes such as all-cause mortality, MI and stroke. They included trials which examined the efficacy of a statin on cardiovascular outcomes with a duration of at least 2 years, which enrolled more than 1,000 participants and where the comparator was either placebo or usual care.

Statin use and cardiovascular disease outcomes

A total of 21 trials with 1,255 to 20,536 participants, of which 33% were for primary prevention, were included in the analysis. The average trial follow-up period was 4.4 years and ranged from 1.9 to 6.1 years.

From the meta-analysis, the overall absolute risk reduction (ARR) for all-cause mortality was 0.8%, 1.3% for MI and 0.4% for stroke for individuals randomised to receive a statin compared to either placebo or usual care. The corresponding relative risk reductions (RRRs) were 9% (all-cause mortality), 29% (MI) and 14% (stroke). As an example, the authors calculated that with an ARR of 1.3% for MI, 77 patients (i.e., 1/0.013) would need to be treated for an average of 4.4 years to prevent one myocardial infarction.

In subgroup analysis (primary vs secondary prevention), the ARR was 0.6%, 0.7% and 0.3% for all-cause mortality, MI and stroke respectively, in primary prevention trials. The corresponding RRRs were 13%, 38% and 24%.

For secondary prevention, the ARRs were 0.9% (all-cause mortality), 2.2% (MI) and 0.7% (stroke) with the corresponding RRRs of 14%, 27% and 13%.

The researchers also examined the the potential mediating effect of LDL cholesterol reduction with the absolute and relative treatment effects but these findings were inconclusive. In other words, it was not possible to either prove or disprove an association between the magnitude of LDL cholesterol reduction and the size of a treatment effect.

An important finding from the analysis was the high level of statistically heterogeneity in the studies, ranging from 27% to 82%, which suggested that pooling of results could make the findings unreliable.

The authors concluded that the absolute risk reductions associated with the use of a statin drug are modest in comparison to the often quoted relative risk reductions. However, they added that given the high level of heterogeneity, these results should be interpreted with caution. Despite this limitation, they suggested that clinicians should communicate both ARRs and RRRs to patients to enable informed decision-making about the benefits of statin treatment.

Citation
Byrne P et al. Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis Ann Intern Med 2022

Seroconversion rates low after COVID-19 vaccination among immunocompromised

18th March 2022

Seroconversion rates among immunocompromised patients are low after the first COVID-19 vaccine dose but increase upon receipt of the second

Seroconversion rates after a single COVID-19 vaccination among immunocompromised patients is low but improves after a second dose according to the findings of a systematic review and meta-analysis by researchers from the Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Immunocompromised patients are at an increased risk severe COVID-19 illness and death. Moreover, it is recognised that among immunocompromised, solid organ transplant patients, a wide range of respiratory viruses cause significant morbidity and mortality among transplant recipients. In a 2020 review of COVID-19 in cancer patients, it was noted how those with cancer are susceptible to severe clinically adverse events and a higher mortality from COVID-19 infection as well as morbidity and mortality from their underlying malignancy. Although one 2018 systematic review found that  seroconversion and sero-protection rates for influenza antigens were low in solid organ transplant recipients, no such reviews on the immunogenicity of COVID-19 vaccines and the overall seroconversion rates among cohorts of immunocompromised patients and been undertaken.

For the present study, the Singaporean team compared the seroconversion rates among groups of immunocompromised patients compared to immunocompetent controls. The team searched for studies that included patients with active cancer of solid organs, haematological cancers, organ transplant recipients, those with active immune mediated inflammatory disorders and for which a comparator group was included. The primary outcomes of interest were seroconversion after the first and second COVID-19 vaccine doses.

Seroconversion rates after vaccination

A total of 82 studies were included in the meta-analysis.

Among those with haematological cancers, compared to immunocompetent individuals, the seroconversion rate after the first vaccination was less than half (risk ratio, RR = 0.40, 95% CI 0.32 – 0.50) and similar for those with solid cancers (RR = 0.55, 95% CI 0.46 – 0.65) and immune mediated inflammatory disorders (RR = 0.53, 95% CI 0.39 – 0.71). However, it was significantly lower for organ transplant patients (RR = 0.06, 95% CI 0.04 – 0.09).

After the second vaccination, the rates of seroconversion increased. For example, for haematological cancers (RR = 0.63) and among those with solid cancer (RR = 0.90) and whilst higher, remained very low, among organ transplant patients (RR = 0.39).

The authors did not include studies where a third COVID-19 dose had been administered in the meta-analysis because most studies did not include a comparator for control purposes. Nevertheless, based solely on a systematic review, they found that conversion rates for organ transplant patients improved by 36 and 66.7%.

The authors concluded that administration of a third vaccine dose (which has now become standard practice for everyone) is warranted for immunocompromised patients.

Citation
Lee ARYB et al. Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis BMJ 2022

Mortality benefit from higher daily steps plateaus

15th March 2022

The mortality benefit achieved through doing more daily steps increases but only up to a certain point and then plateaus

A mortality benefit accrues from taking more daily steps but this benefit plateaus and depends upon an individual’s age. This was the main finding of a meta-analysis by a team from the Department of Kinesiology and Institute for Applied Life Sciences, University of Massachusetts Amherst, Massachusetts, US.

Measuring the number of steps taken each day has become much easier over the last few years largely because of an increase in the availability of fitness trackers. Moreover, though the idea that the target for beneficial health is at least 10,000 steps/day, there is a lack of evidence to justify this figure. Indeed, it is possible that the actual number of steps/day required could be actually much lower, with one study in older women finding that the mortality rates progressively decreased before levelling at approximately 7500 steps/day. In addition, the optimal number of steps needed to achieve a mortality benefit is likely to be influenced by other factors such as age and gender, as well as the pace of walking, although observational studies have found that there is no significant association between step intensity and mortality after adjusting for total steps per day.

For the present study, the US team set out to assess the mortality benefit derived from the number of steps taken per day and considered how this might be affected by both age and gender. They also sought to clarify if there was an association between the stepping rate (i.e., how fast someone walked) and all-cause mortality. They searched for studies which examined the relationship between daily steps and mortality in adults (> 18 years of age). After identifying relevant articles, the US team asked the study investigators to provide additional data and to calculate the peak 30 and 60 minute stepping rates, as well as the time spent walking at 40 steps/min or faster and 100 steps/min. The primary outcome was set as all-cause mortality. The total number of median daily steps was categorised into quartiles; up to 3553 (quartile 1); 5801 (quartile 2); 7842 (quartile 3) and 10,901 (quartile 4). Hazard ratios were calculated for the mortality benefits and adjusted for several factors including age, sex, education level, body mass index and other health-related variables.

Mortality benefit and daily step count

The authors identified a total of 15 eligible studies which included 47,471 individuals with a mean age of 65 years (68% female) and who were followed-up for a median of 7.1 years. The overall median number of steps was 6495 and individuals under 60 years of age had a higher median number of daily steps compared to those over 60. (7803 vs 5649, under 60 years vs over 60 years of age). In the cohort as a whole, there were 3013 deaths recorded.

Compared to the lowest quartile, the overall adjusted hazard ratio for all-cause mortality in the highest quartile was 0.47 (95% CI 0.39 – 0.57). When comparing those under versus over 60 years of age, there was a greater mortality benefit for older individuals (HR = 0.60 vs HR = 0.43, under 60 vs over 60). In addition, there was a higher benefit for women compared to men (HR = 0.43 vs HR = 0.52, female vs male).

The hazard ratios for mortality plateaued for adults 60 years and older at 6000 – 8000 steps/day and between 8,000 – 10,000 for those under 60 years of age.

The mortality benefit was also significant for a higher step rate for both 30 and 60 minutes but not significant for the time spent walking at 40 or faster, at 100 steps/minute. In other words, didn’t seem to matter if someone walked faster.

The authors concluded that while mortality benefits can be achieved at below the popular reference value of 10,000 steps/day, these benefits plateau and are not increased by taking further steps.

Citation
Paluch AE et al. Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts Lancet Public Health 2022