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Journal of Translational Medicine Oct 2023Med-Index is a one-health front-of-pack (FOP) label, based on Mediterranean diet (MedDiet) principles, developed to summarize information about the nutritional... (Review)
Review
Scientific evidence supporting the newly developed one-health labeling tool "Med-Index": an umbrella systematic review on health benefits of mediterranean diet principles and adherence in a planeterranean perspective.
BACKGROUND
Med-Index is a one-health front-of-pack (FOP) label, based on Mediterranean diet (MedDiet) principles, developed to summarize information about the nutritional properties and related-health benefits of any food as well as its sustainable production processes, and the associated food company's social responsibility parameters in a new "Planeterranean" perspective. Thus, Med-Index can be adopted in and by any European region and authority as well as worldwide; this is achieved by consumption and cooking of locally available and sourced foods that respect MedDiet principles, both in terms of healthy nutrition and sustainable production. The huge body of scientific evidence about the health benefits of the MedDiet model and principles requires a comprehensive framework to encompass the scientific reliability and robustness of this tool. A systematic review was carried out to examine the association between human health and adherence to MedDiet patterns upon which the "Med-Index" tool was subsequently developed.
METHODS
MEDLINE and PubMed databases were searched for eligible publications from 1990 to April 2023. Systematic literature reviews, with or without meta-analysis, of clinical trials and observational studies were screened by two independent investigators for eligibility, data extraction, and quality assessment. English language and the time interval 1990-2023 were applied. A registry code CRD42023464807 was generated on PROSPERO and approved for this search protocol. The corrected covered area (CCA), calculated to quantify the degree of overlap between reviews, gave a slight overlap (CCA = 4%).
RESULTS
A total of 84 systematic reviews out of 6681 screened records were selected. Eligible reviews included studies with predominantly observational designs (61/84, 72.6%%), of which 26/61 referenced studies of mixed observational and RCT designs, while 23/84 (27.4%) were RCT-only systematic reviews. Seventy-nine different entries were identified for health outcomes, clustered into 10 macro-categories, each reporting a statistically significant association with exposure to the MedDiet. Adherence to MedDiet was found to strongly benefit age-related chronic diseases (21.5%), neurological disorders (19%), and obesity-related metabolic features (12.65), followed by CVDs (11.4%), cancer (10.1%), diabetes (7.5%), liver health (6.3%), inflammation (5%), mortality (5%), and renal health (1.2%). The quality of the studies was moderate to high.
CONCLUSION
In the context of a "Planeterranean" framework and perspective that can be adopted in any European region and worldwide, MedDiet represents a healthy and sustainable lifestyle model, able to prevent several diseases and reduce premature mortality. In addition, the availability of a FOP, such as Med-Index, might foster more conscious food choices among consumers, paying attention both to human and planetary health.
Topics: Humans; Diet, Mediterranean; Reproducibility of Results; One Health; Diabetes Mellitus; Cardiovascular Diseases
PubMed: 37885010
DOI: 10.1186/s12967-023-04618-1 -
Pharmacological Research May 2024Patients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO)... (Review)
Review
Patients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO) and its receptor have neuroprotective effects in cell and animal models of nervous system disorders. Recombinant human EPO (rHuEPO), commonly used to treat anemia in CKD patients, could be a neuroprotective agent. In this systematic review, we aimed to assess the published studies investigating the cognitive benefits of rHuEPO treatment in individuals with reduced kidney function. We comprehensively searched Pubmed, Cochrane Library, Scopus, and Web of Science databases from 1990 to 2023. After selection, 24 studies were analyzed, considering study design, sample size, participant characteristics, intervention, and main findings. The collective results of these studies in CKD patients indicated that rHuEPO enhances brain function, improves performance on neuropsychological tests, and positively affects electroencephalography measurements. These findings suggest that rHuEPO could be a promising neuroprotective agent for managing CKD-related cognitive impairment.
Topics: Humans; Erythropoietin; Neuroprotective Agents; Renal Insufficiency, Chronic; Cognitive Dysfunction; Animals; Recombinant Proteins; Brain; Cognition
PubMed: 38493928
DOI: 10.1016/j.phrs.2024.107146 -
Acta Bio-medica : Atenei Parmensis Dec 2023The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to...
BACKGROUND
The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors.
METHODS
We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk.
RESULTS
Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders.
CONCLUSION
Monitoring and early diagnosis of these conditions are of paramount importance for successful management.
Topics: Female; Humans; Male; Child; Diabetes Mellitus, Type 2; Gonadotropin-Releasing Hormone; Puberty, Precocious; Obesity; Puberty
PubMed: 38054666
DOI: 10.23750/abm.v94i6.15316 -
American Journal of Clinical and... 2023Tacrolimus is an immunosuppressant with a narrow therapeutic index and pharmacokinetic variability. This variability may be attributed to genetic variants in gene... (Review)
Review
Tacrolimus is an immunosuppressant with a narrow therapeutic index and pharmacokinetic variability. This variability may be attributed to genetic variants in gene associated with Tacrolimus metabolism. Studies focusing on genetic variants in the gene associated with Tacrolimus metabolism have been published, a meta-analysis of these published articles may provide a direction that can change the future research and clinical management of renal transplant patients. In this systematic review and meta-analysis, we have reviewed and analyzed the studies and clinical trials conducted to determine the association between genetic variants of and Tacrolimus metabolism from the PubMed database and clinical trials (www.clinicaltrials.gov). This meta-analysis also assessed the correlation of genotype (rs776746) with concentration/dose (C/D) of Tacrolimus in renal transplant patients. The 59 published articles on genetic association of the on Tacrolimus doses were reviewed for this systematic review. Meta-analysis showed that the Tacrolimus C/D ratio is significantly lower in the expressor group as compared with non-expressor in Asian, European as well as in mixed populations at any post-transplant period (P<0.0001). Our study further confirmed that the variant (rs776746) is clinically relevant for the dose determination of Tacrolimus. Variations in Tacrolimus C/D have been found to be significantly linked to the patient's genetic variant (rs776746). The addition of other genetic variants involved in the pharmacokinetic of Tacrolimus may determine efficient regimen for drug dose. Our meta-analysis confirmed that the genetic variant (rs776746) analysis is relevant in personalizing the Tacrolimus dose determination in renal transplant patients.
PubMed: 37645617
DOI: No ID Found -
Cardiovascular Diabetology Jan 2024Numerous clinical studies have explored sodium-glucose cotransporter 2 inhibitor (SGLT2i) in patients with chronic heart failure (CHF), with or without type 2 diabetes... (Meta-Analysis)
Meta-Analysis
PURPOSE
Numerous clinical studies have explored sodium-glucose cotransporter 2 inhibitor (SGLT2i) in patients with chronic heart failure (CHF), with or without type 2 diabetes mellitus (T2DM), and SGLT2i were proved to significantly reduce CHF hospitalization, cardiovascular death, cardiovascular mortality, all-cause mortality and myocardial infarction in patients with or without T2DM. However, only a limited few have investigated the effects of SGLT-2i on HF disease-specific health status and cardiac function. This meta-analysis aims to assess the effects of SGLT2i on disease-specific health status and cardiac function in CHF patients.
METHODS
A comprehensive search was conducted of trials by searching in PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, and two Chinese databases (CNKI and Wanfang), Clinical Trials ( http://www.
CLINICALTRIALS
gov ) were also searched.
RESULTS
A total of 18 randomized controlled trials (RCTs) involving 23,953 participants were included in the meta-analysis. The effects of SGLT2 inhibitors were compared with control or placebo groups in CHF with or without T2DM. The SGLT2 inhibitors group exhibited a significant reduction in pro b-type natriuretic peptide (NT-proBNP) levels by 136.03 pg/ml (95% confidence interval [CI]: -253.36, - 18.70; P = 0.02). Additionally, a greater proportion of patients in the SGLT2 inhibitors group showed a ≥ 20% decrease in NT-proBNP (RR = 1.45, 95% CI [0.92, 2.29], p = 0.072). However, no statistically significant difference was observed for the effects on B-type natriuretic peptide (BNP). The use of SGLT-2 inhibitors led to a noteworthy improvement in LVEF by 2.79% (95% CI [0.18, 5.39];P = 0.036). In terms of health status, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and 6-minute walk distance, SGLT2 inhibitors led to a significant improvement in KCCQ clinical summary (KCCQ-CS) score (WMD = 1.7, 95% CI [1.67, 1.73], P < 0.00001), KCCQ overall summary (KCCQ-OS) score (WMD = 1.73, 95% CI [0.94, 2.52], P < 0.00001), and KCCQ total symptom (KCCQ-TS) score (WMD = 2.88, 95% CI [1.7, 4.06], P < 0.00001). Furthermore, the occurrence of KCCQ-CS and KCCQ-OS score increases ≥ 5 points had relative risks (RR) of 1.25 (95% CI [1.11, 1.42], P < 0.00001) and 1.15 (95% CI [1.09, 1.22], P < 0.00001), respectively. Overall, SGLT2 inhibitors increased the 6-minute walk distance by 23.98 m (95% CI [8.34, 39.62]; P = 0.003) compared to control/placebo from baseline.
CONCLUSIONS
The SGLT2 inhibitors treatment offers an effective strategy for improving NT-proBNP levels, Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance in CHF with or without T2DM. These findings indicate that SGLT2i improve cardiac function and health status in CHF with or without T2DM, and provide valuable guidance for clinicians making treatment decisions for patients with CHF.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Natriuretic Peptide, Brain; Heart Failure; Health Status; Diabetes Mellitus, Type 2; Chronic Disease; Cardiomyopathies; Randomized Controlled Trials as Topic
PubMed: 38172861
DOI: 10.1186/s12933-023-02042-9 -
Systematic Reviews Jul 2023The purpose of this systematic review is to collect, appraise, and synthesize existing evidence from systematic reviews and meta-analyses (SRs/MAs) on the effectiveness...
OBJECTIVE
The purpose of this systematic review is to collect, appraise, and synthesize existing evidence from systematic reviews and meta-analyses (SRs/MAs) on the effectiveness of tolvaptan for water retention in heart failure.
METHODS
A comprehensive literature search was performed on PubMed, EMBASE, web of science, Cochrane reviews for SRs/Mas published between the databases' establishment to November 17, 2021. All the records were managed with Endnote 20. Standardized forms were used to extract data. Revman 5.3 was used to make forest plots to show the characteristics of outcomes. The methodological and evidence quality were respectively evaluated by AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews 2) and GRADE (Grading of Recommendation of Assessment, Development, and Evaluation) system.
RESULTS
A total of 9 SRs/Mas between 2015 to 2020 met inclusion criteria. Serum sodium concentration and urine output were considered as primary outcomes and body weight change and all-cause mortality as second outcomes. Through conducting forest plots, it appeared that tolvaptan brought more positive effect than conventional therapies. It was pessimistic when it comes to the quality of the 9 studies. all the 9 articles were rated as low-quality because AMSTAR 2 evaluation showed that they each had at least one critical item (items 2, 4, 7, 9, 11, 13 and 15) defect. Besides, every article had a few non-critical item defects too. The result of GRADE assessment was not optimistic, so the overall quality of the evidences was low as well.
CONCLUSION
Tolvaptan can be recommended for water retention in HF patients, but more evidence is needed.
Topics: Humans; Tolvaptan; Water-Electrolyte Balance; Heart Failure; Databases, Factual; Water
PubMed: 37516894
DOI: 10.1186/s13643-023-02293-3 -
Genes Aug 2023: Although common drugs for treating type 2 diabetes (T2D) are widely used, their therapeutic effects vary greatly. The interaction between the gut microbiome and... (Review)
Review
: Although common drugs for treating type 2 diabetes (T2D) are widely used, their therapeutic effects vary greatly. The interaction between the gut microbiome and glucose-lowering drugs is one of the main contributors to the variability in T2D progression and response to therapy. On the one hand, glucose-lowering drugs can alter gut microbiome components. On the other hand, specific gut microbiota can influence glycemic control as the therapeutic effects of these drugs. Therefore, this systematic review assesses the bi-directional relationships between common glucose-lowering drugs and gut microbiome profiles. A systematic search of Embase, Web of Science, PubMed, and Google Scholar databases was performed. Observational studies and randomised controlled trials (RCTs), published from inception to July 2023, comprising T2D patients and investigating bi-directional interactions between glucose-lowering drugs and gut microbiome, were included. Summarised findings indicated that glucose-lowering drugs could increase metabolic-healthy promoting taxa (e.g., and decrease harmful taxa (e.g., and ). Our findings also showed a significantly different abundance of gut microbiome taxa (e.g., (i.e., )) in T2D patients with poor compared to optimal glycemic control. This review provides evidence for glucose-lowering drug and gut microbiome interactions, highlighting the potential of gut microbiome modulators as co-adjuvants for T2D treatment.
Topics: Humans; Gastrointestinal Microbiome; Bacteroides; Bifidobacterium; Diabetes Mellitus, Type 2; Glucose
PubMed: 37628624
DOI: 10.3390/genes14081572 -
Scientific Reports Jan 2024Non-alcoholic fatty liver disease (NAFLD) is a substantial contributor to liver-related morbidity worldwide, and yet, there are no standard, universal pharmacologic... (Meta-Analysis)
Meta-Analysis
Efficacy of sodium glucose cotransporter 2 inhibitors on hepatic fibrosis and steatosis in non-alcoholic fatty liver disease: an updated systematic review and meta-analysis.
Non-alcoholic fatty liver disease (NAFLD) is a substantial contributor to liver-related morbidity worldwide, and yet, there are no standard, universal pharmacologic therapies approved for this indication. The aim of this systematic review and meta-analysis is to evaluate the effectiveness of SGLT-2 inhibitors in improving hepatic steatosis and hepatic fibrosis in patients with NAFLD. An extensive electronic database search was done to identify studies published from inception until December 2023, without any language restrictions. All randomized controlled trials (RCT) that evaluated the use of SGLT-2 inhibitors for patients with NAFLD, regardless of diabetes mellitus status, were included. The Cochrane Risk of Bias 2.0 tool was used to assess the risk of bias of each study included. Evidence from all studies were synthesized as mean differences for continuous data, and as risk ratio for dichotomous outcomes. An inverse variance or Mantel-Haenszel test was used in conjunction with a random-effects meta-analysis model, where necessary. 18 eligible RCTs involving 1330 participants were analyzed, all of which had risk of bias ranging from low to some concerns. Significant difference in means was observed for controlled attenuation parameter (6 trials, n = 372; MD: - 10.59 dB/m, 95% CI [- 18.25, - 2.92], p = 0.007, I = 0%); L/S ratio (3 trials, n = 163; MD: 0.11, 95% CI [0.01, 0.21], p = 0.04, I = 78%); LSM (7 trials, n = 447; MD: - 0.67 kPa, 95% CI [- 1.19, - 0.16], p = 0.010, I = 69%); MRI-PDFF (5 trials, n = 330; MD: - 2.61%, 95% CI [- 5.05, - 0.17], p = 0.04, I = 78%), and FIB-4 index (10 trials, n = 648; MD: - 0.12, 95% CI [- 0.21, - 0.04], p = 0.005, I = 16%) after SGLT-2 inhibitor treatment as compared to controls. In conclusion, the use of SGLT-2 inhibitors may lead to slight improvement of hepatic steatosis and/or fibrosis as compared to controls in patients with NAFLD and Type 2 diabetes mellitus based on imaging and histopathology biomarkers with low to moderate certainty of evidence.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Sodium-Glucose Transporter 2 Inhibitors; Liver Cirrhosis; Databases, Factual
PubMed: 38267513
DOI: 10.1038/s41598-024-52603-5 -
ESC Heart Failure Feb 2024Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors,... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.
Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P = 0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).
Topics: Humans; Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Heart Failure; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Potassium; Renin-Angiotensin System
PubMed: 38012095
DOI: 10.1002/ehf2.14588 -
The Cochrane Database of Systematic... Nov 2023Oral nirmatrelvir/ritonavir (Paxlovid) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. It... (Review)
Review
BACKGROUND
Oral nirmatrelvir/ritonavir (Paxlovid) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. It remains to be evaluated for which indications and patient populations the drug is suitable.
OBJECTIVES
To assess the efficacy and safety of nirmatrelvir/ritonavir plus standard of care (SoC) compared to SoC with or without placebo, or any other intervention for treating COVID-19 or preventing SARS-CoV-2 infection. To explore equity aspects in subgroup analyses. To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in-between publication of review updates.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, Scopus, and World Health Organization COVID-19 Research Database, identifying completed and ongoing studies without language restrictions and incorporating studies up to 15 May 2023. This is a LSR. We conduct update searches every two months and make them publicly available on the open science framework (OSF) platform.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing nirmatrelvir/ritonavir plus SoC to SoC with or without placebo, or any other intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS-CoV-2 infection. We screened all studies for research integrity. Studies were ineligible if they had been retracted, or if they were not prospectively registered including appropriate ethics approval.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology and used the Cochrane RoB 2 tool. We rated the certainty of evidence using the GRADE approach for the following outcomes: 1. to treat outpatients with mild COVID-19; 2. to treat inpatients with moderate to severe COVID-19: mortality, clinical worsening or improvement, quality of life, (serious) adverse events, and viral clearance; 3. to prevent SARS-CoV-2 infection in postexposure prophylaxis (PEP); and 4. pre-exposure prophylaxis (PrEP) scenarios: SARS-CoV-2 infection, development of COVID-19 symptoms, mortality, admission to hospital, quality of life, and (serious) adverse events. We explored inequity by subgroup analysis for elderly people, socially-disadvantaged people with comorbidities, populations from low-income countries and low- to middle-income countries, and people from different ethnic and racial backgrounds.
MAIN RESULTS
As of 15 May 2023, we included two RCTs with 2510 participants with mild and mild to moderate symptomatic COVID-19 in outpatient and inpatient settings comparing nirmatrelvir/ritonavir plus SoC to SoC with or without placebo. All trial participants were without previous confirmed SARS-CoV-2 infection and at high risk for progression to severe disease. Randomization coincided with the Delta wave for outpatients and Omicron wave for inpatients. Outpatient trial participants and 73% of inpatients were unvaccinated. Symptom onset in outpatients was no more than five days before randomisation and prior or concomitant therapies including medications highly dependent on CYP3A4 were not allowed. We excluded two studies due to concerns with research integrity. We identified 13 ongoing studies. Three studies are currently awaiting classification. Nirmatrelvir/ritonavir for treating people with asymptomatic or mild COVID-19 in outpatient settings Nirmatrelvir/ritonavir plus SoC compared to SoC plus placebo may reduce all-cause mortality at 28 days (risk ratio (RR) 0.04, 95% confidence interval (CI) 0.00 to 0.68; 1 study, 2224 participants; low-certainty evidence) and admission to hospital or death within 28 days (RR 0.13, 95% CI 0.07 to 0.27; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus SoC may reduce serious adverse events during the study period compared to SoC plus placebo (RR 0.24, 95% CI 0.15 to 0.41; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus SoC probably has little or no effect on treatment-emergent adverse events (RR 0.95, 95% CI 0.82 to 1.10; 1 study, 2224 participants; moderate-certainty evidence), and probably increases treatment-related adverse events such as dysgeusia and diarrhoea during the study period compared to SoC plus placebo (RR 2.06, 95% CI 1.44 to 2.95; 1 study, 2224 participants; moderate-certainty evidence). Nirmatrelvir/ritonavir plus SoC probably decreases discontinuation of study drug due to adverse events compared to SoC plus placebo (RR 0.49, 95% CI 0.30 to 0.80; 1 study, 2224 participants; moderate-certainty evidence). No studies reported improvement of clinical status, quality of life, or viral clearance. Nirmatrelvir/ritonavir for treating people with moderate to severe COVID-19 in inpatient settings We are uncertain whether nirmatrelvir/ritonavir plus SoC compared to SoC reduces all-cause mortality at 28 days (RR 0.63, 95% CI 0.21 to 1.86; 1 study, 264 participants; very low-certainty evidence), or increases viral clearance at seven days (RR 1.06, 95% CI 0.71 to 1.58; 1 study, 264 participants; very low-certainty evidence) and 14 days (RR 1.05, 95% CI 0.92 to 1.20; 1 study, 264 participants; very low-certainty evidence). No studies reported improvement or worsening of clinical status and quality of life. We did not include data for safety outcomes due to insufficient and inconsistent information. Subgroup analyses for equity For outpatients, the outcome 'admission to hospital or death' was investigated for equity regarding age (less than 65 years versus 65 years or greater) and ethnicity. There were no subgroup differences for age or ethnicity. For inpatients, the outcome 'all-cause mortality' was investigated for equity regarding age (65 years or less versus greater than 65 years). There was no difference between subgroups of age. No further equity-related subgroups were reported, and no subgroups were reported for other outcomes. Nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection (PrEP and PEP) No studies available.
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests nirmatrelvir/ritonavir reduces the risk of all-cause mortality and hospital admission or death in high-risk, unvaccinated COVID-19 outpatients infected with the Delta variant of SARS-CoV-2. There is low- to moderate-certainty evidence of the safety of nirmatrelvir/ritonavir. Very low-certainty evidence exists regarding the effects of nirmatrelvir/ritonavir on all-cause mortality and viral clearance in mildly to moderately affected, mostly unvaccinated COVID-19 inpatients infected with the Omicron variant of SARS-CoV-2. Insufficient and inconsistent information prevents the assessment of safety outcomes. No reliable differences in effect size and direction were found regarding equity aspects. There is no available evidence supporting the use of nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection. We are continually updating our search and making search results available on the OSF platform.
Topics: Humans; Aged; COVID-19; SARS-CoV-2; Ritonavir; COVID-19 Drug Treatment
PubMed: 38032024
DOI: 10.1002/14651858.CD015395.pub3