To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people.
Systematic review and meta-analysis.
PubMed, Embase, Central Register of Controlled Trials, COVID-19 ...Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies.
Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants.
A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed.
82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I
=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I
=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I
=89%; 0.29, 0.11 to 0.58, I
=97%), and solid cancers (0.55, 0.46 to 0.65, I
=78%; 0.44, 0.36 to 0.53, I
=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I
=0%; 0.06, 0.04 to 0.08, I
=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I
=92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I
=88%; 0.62, 0.54 to 0.70, I
=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I
=92%; 0.77, 0.66 to 0.85, I
=93%), and solid cancers (0.90, 0.88 to 0.93, I
=51%; 0.89, 0.86 to 0.91, I
=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I
=0%; 0.97, 0.83 to 1.00, I
=89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines.
Seroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed.
PROSPERO CRD42021272088.
Non-alcoholic fatty liver disease is highly prevalent in patients with type 2 diabetes mellitus. Studies on glucagon-like peptide-1 receptor agonists for the treatment of non-alcoholic fatty liver ...disease have reported promising results. Despite this, there has been limited evidence of its efficacy in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus. This meta-analysis examined existing evidence on the efficacy of glucagon-like peptide-1 receptor agonists on the management of non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus.
Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles discussing the efficacy of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Values of standardized mean differences (SMD) and risk ratio (RR) were determined for continuous outcomes and dichotomous outcomes respectively.
8 studies involving 1,454 patients from 5 randomized controlled trials and 3 cohort studies were included in the analysis. Our analysis found significant improvements in hepatic fat content, liver biochemistry, body composition, glucose parameters, lipid parameters, insulin sensitivity and inflammatory markers following glucagon-like peptide-1 receptor agonist treatment. Glucagon-like peptide-1 receptor agonists significantly decreased hepatic fat content compared to metformin and insulin-based therapies. Glucagon-like peptide-1 receptor agonists also improved fibrosis markers, but this did not reach statistical significance.
With a high prevalence of obesity and non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonist treatment shows promise in improving both diabetes and non-alcoholic fatty liver disease phenotype.
Non-alcoholic fatty liver disease (NAFLD) is a very common disorder among patients with type 2 diabetes and may share causal relationship. Type 2 diabetes is a risk factor for progression and ...potential poor outcomes in NAFLD patients. This meta-analysis aimed to analyze the current evidence of sodium-glucose co-transporter-2 inhibitors (SGLT2i), a glucose-lowering drug to improve NAFLD in patients with Type 2 Diabetes.
Medline, Embase and Cochrane Central Register of Controlled Trials were searched for articles examining efficacy of SGLT2i on treatments of NAFLD in type 2 diabetes in July 2020, and articles were sieved. Continuous data were extracted in the form of mean and standard deviation and were pooled with standardized mean difference (SMD).
10 articles involving 555 patients from seven randomized controlled trials (RCTs) and three cohort studies, were included in this meta-analysis. Our analysis revealed significant improvements in hepatic fat content (after treatment: -0.789 (-1.404 to -0.175), p = 0.012; compared with control: -0.923 (-1.562 to -0.285), p = 0.005), AST (After Treatment: -0.539 (-0.720 to -0.357), p < 0.001; compared with control: -0.421 (-0.680 to -0.161), p = 0.001), ALT (after treatment: -0.633 (-0.892 to -0.373), p < 0.001; compared with Control: -0.468 (-0.685 to -0.251), p < 0.001), body composition (BMI: after treatment: -0.225 (-0.456 to 0.005), p = 0.055; compared with Control: -1.092 (-2.032 to -0.153), p = 0.023), glycemic control (HbA1c: After Treatment: -0.701 (-1.098 to -0.303), p = 0.001; compared with control: -0.210 (-0.603 to 0.183), p = 0.295), lipid parameters (Triglycerides: after treatment: -0.230 (-0.409 to -0.052), p = 0.011; compared with control: -0.336 (-0.597 to -0.076), p = 0.011), inflammatory markers (serum ferritin: after treatment: -0.409 (-0.694 to -0.124), p = 0.005; compared with control: -0.814 (-1.688 to 0.059), p = 0.068) after SGLT2i treatment, and when compared against controls. There was a trend in the improvement in fibrosis markers after SGLT2i treatment.
SGLT2i is an effective treatment to improve NAFLD among patients with type 2 diabetes. Further studies are needed to understand the direct and indirect effects of SGLT2i on NAFLD and if SGLT2i could prevent the progression of NAFLD or NASH. SGLT2i could potentially be considered for patients with type 2 diabetes and NAFLD, if there are no contraindications.
There is a growing number of trials examining the effectiveness of pharmacotherapies for obesity, however, little is known about placebo and nocebo effect in these trials. Hence, we sought to examine ...the effect of placebo in obesity trials, to better understand the potential factors affecting clinical endpoints in them.
Medline, Embase, and Cochrane CENTRAL were searched for articles examining weight-loss RCTs examining patients with overweight or obesity in placebo-controlled arms from inception till 25 June 2022. This paper was registered online with PROSPERO (CRD42022302482). A single arm meta-analysis of proportions was used to estimate the primary outcomes, ≥5%, ≥10%, and ≥15% total weight loss – and the adverse effects that patients experienced during the trial. A meta-analysis of means was used to estimate the pooled mean differences of the secondary outcomes including, body weight measurements, lipid levels, glycemic indices, and blood pressure over time.
A total of 63 papers involving 20,454 patients and 69 trials were included. The proportion of patients that had ≥5%, ≥10%, and ≥15% weight loss was 20·4% (CI:16·1% to 25·0%), 8·3% (CI:6·1% to 10·9%), and 6·2% (CI:3·8% to 9·7%), respectively. Analysis by duration of trials showed stepwise increase in proportion of patients with ≥5% and ≥10% weight loss with increasing duration of study. Analysis of secondary outcomes found modest improvement in all analyses. The pooled average rate of overall AEs, serious AEs, and discontinuation was 73·7% (CI:68·0% to 79·0%), 3·4% (CI:2·4% to 4·5%), and 5·2% (CI:4·0% to 6·5%), respectively. In psychiatric complications, the pooled rates of anxiety and depression were 2·7% (CI:1·8% to 3·7%) and 2·5 (CI:1·7% to 3·3%).
Our meta-analysis of placebo-treated participants in weight-loss RCTs indicate a significant placebo and nocebo effect. These findings are important to quantify their effect and may inform the design of future RCTs.
This research did not receive additional support from organizations beyond the authors’ academic institutions.
NODAT (new-onset diabetes after transplantation) is an important complication after liver transplant, however, there is variation in the reported incidence of NODAT. Therefore, a meta-analysis was ...performed to estimate the incidence of NODAT in liver transplant. Electronic databases were searched for articles regarding NODAT incidence after liver transplantation. Incidence of NODAT were analyzed at six different timepoints. Summary statistics were calculated using a generalized linear mixed model in random effects. 28 articles were included and out of a pooled population of 71,257 patients, overall incidence of NODAT was found to be 15.51%, 16.09%, 18.30%, 20.86%, 18.08%, 25.05% for three-months, six-months, one-year, three-year, five-year, and ten-year timepoints respectively. After a sensitivity analysis which only included articles with clear definitions of NODAT, the incidence of NODAT was found to be higher at three-year (21.79%), five-year (25.82%), and ten-year (44.95%) timepoints. Subgroup analysis according to ethnicity found no significant differences for all timepoints. However, studies with predominantly Asian participants generally had a higher incidence of NODAT. In conclusion, this meta-analysis provides a pooled estimate of the incidence of NODAT following liver transplantation. Further studies are required to provide a more comprehensive understanding on how ethnicity can affect the incidence of NODAT.
(1) Background: Treatment of dyslipidemia via statin therapy in the non-liver transplant (LT) population is associated with a mortality benefit; however, the impact of statin therapy in post-LT ...population is not well-defined. This meta-analysis seeks to investigate the safety and efficacy of statin therapy in post-LT patients. (2) Methods: A systematic literature search on Medline and EMBASE database was conducted. A single-arm proportional meta-analysis and conventional pair-wise meta-analysis were performed to compare different outcomes with a random effects model. (3) Results: A total of 11 studies were included in this study, with 697 LT recipients identified to be on statin therapy. Statins were underutilized with only 32% (95% CI: 0.15–0.52) of 1094 post-LT patients on therapy. The incidence of adverse events of 14% (95% CI: 0.05–0.25) related to statin therapy was low. A significant mortality benefit was noted in patients on statin therapy with HR = 0.282 (95% CI: 0.154–0.517, p < 0.001), and improved lipid profiles post LT. The use of statins also significantly decreased odds of graft rejection (OR = 0.33; 95% CI: 0.15–0.73) and hepatocellular carcinoma (HCC) recurrence (HR = 0.32, 95% CI: 0.11–0.89). (4) Conclusions: Statin therapy is safe and efficacious in post-LT patients. Future studies to evaluate the effects of interactions between statins and immunosuppressant therapy are warranted.
In light of a global organ shortage, living donor transplantation has become increasingly relevant as an alternative to deceased donor transplantation. While current research has revolved around the ...medical aspects of transplantation, there remains a paucity of literature regarding the quality of life (QOL) of living donors. Hence, this review aims to provide a comprehensive outline of the current landscape of living liver and kidney transplantation, with a focus on the mental health and wellbeing of donors. As highlighted in previous studies, organ donation has a significant impact on both physical and mental aspects of donor wellbeing, with marked deteriorations occurring in the short term. Furthermore, other qualitative aspects such as financial burden contribute greatly to donor distress, reflecting a need for improved donor care. To address these pertinent issues, recommendations for a successful transplant program are detailed in this review, which encompasses psychological and social aspects of donor care throughout the donation process. Further research can be done on the impact of recipient deaths on donor QOL and appropriate interventions. Overall, given the selfless sacrifices of living donors, the care of their mental wellbeing is essential. Therefore, greater emphasis should be placed on the provision of adequate psychosocial support for them.
With existing literature focusing on general quality of life, the magnitude and impact of depression among recipients after liver transplantation (LT) is unclear. Hence, we aim to evaluate the ...prevalence, risk factors, and outcomes for recipient-related depression after LT.
Medline and Embase were searched. Single-arm analysis was pooled using the generalized linear mixed model, and logistic regression was performed to analyze risk factors. Pairwise comparative meta-analysis in odds ratio was conducted for binary outcomes.
Of 1069 abstracts, 189 articles underwent full-text review before the inclusion of 48 articles. Pooled depression rate among 5170 recipients was 24.52% (confidence interval CI: 19.46%–30.41%). Depression was most prevalent in Asia compared with other geographical regions. Younger age at transplantation (P = .019) and university education (P = .051) were protective against depression. However, those transplanted for alcoholic liver disease (odds ratio: 1.14, CI: 1.10–1.18, P ≤ 0.001) were more likely to be depressed. Depression resulted in increased odds of mortality (odds ratio: 1.82, CI: 1.08–3.07, P = .04), graft loss (P = .03), and graft rejection (P = .01).
Depression is highly prevalent after LT and may be associated with increased mortality and poorer graft outcomes. More emphasis is needed on the screening of depression among higher risk recipients.
Global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were examined for metabolic diseases (type ...2 diabetes mellitus T2DM, hypertension, and non-alcoholic fatty liver disease NAFLD). For metabolic risk factors (hyperlipidemia and obesity), estimates were limited to mortality and DALYs. From 2000 to 2019, prevalence rates increased for all metabolic diseases, with the greatest increase in high socio-demographic index (SDI) countries. Mortality rates decreased over time in hyperlipidemia, hypertension, and NAFLD, but not in T2DM and obesity. The highest mortality was found in the World Health Organization Eastern Mediterranean region, and low to low-middle SDI countries. The global prevalence of metabolic diseases has risen over the past two decades regardless of SDI. Urgent attention is needed to address the unchanging mortality rates attributed to metabolic disease and the entrenched sex-regional-socioeconomic disparities in mortality.
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•Global estimates from the GBD Study 2019 were examined for metabolic diseases•Mortality rates decreased over time for hyperlipidemia, hypertension, and NAFLD•Mortality rates remained unchanged over time for diabetes and obesity•The highest mortality was in the Eastern Mediterranean and low-income countries
Global estimates from the GBD Study 2019 reveal decreasing mortality rates between 2000 and 2019 for hyperlipidemia, hypertension, and NAFLD, but not for T2DM and obesity. The highest mortality rate due to metabolic disease was found in the Eastern Mediterranean, and in low- to low-middle-income countries. Urgent attention is needed to address high and unchanging mortality rates as well as entrenched sex-regional-socioeconomic disparities in death related to metabolic disease.
LINKED CONTENT
This article is linked to Wijarnpreecha et al papers. To view these articles, visit https://doi.org/10.1111/apt.17424 and https://doi.org/10.1111/apt.17453
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