Conventional laboratory housing increases morbidity and mortality in research rodents: results of a meta-analysis

Abstract Background Over 120 million mice and rats are used annually in research, conventionally housed in shoebox-sized cages that restrict natural behaviours (e.g. nesting and burrowing). This can reduce physical fitness, impair thermoregulation and reduce welfare (e.g. inducing abnormal stereotypic behaviours). In humans, chronic stress has biological costs, increasing disease risks and potentially shortening life. Using a pre-registered protocol (https://atrium.lib.uoguelph.ca/xmlui/handle/10214/17955), this meta-analysis therefore tested the hypothesis that, compared to rodents in ‘enriched’ housing that better meets their needs, conventional housing increases stress-related morbidity and all-cause mortality. Results Comprehensive searches (via Ovid, CABI, Web of Science, Proquest and SCOPUS on May 24 2020) yielded 10,094 publications. Screening for inclusion criteria (published in English, using mice or rats and providing ‘enrichments’ in long-term housing) yielded 214 studies (within 165 articles, using 6495 animals: 59.1% mice; 68.2% male; 31.8% isolation-housed), and data on all-cause mortality plus five experimentally induced stress-sensitive diseases: anxiety, cancer, cardiovascular disease, depression and stroke. The Systematic Review Center for Laboratory animal Experimentation (SYRCLE) tool assessed individual studies’ risks of bias. Random-effects meta-analyses supported the hypothesis: conventional housing significantly exacerbated disease severity with medium to large effect sizes: cancer (SMD = 0.71, 95% CI = 0.54–0.88); cardiovascular disease (SMD = 0.72, 95% CI = 0.35–1.09); stroke (SMD = 0.87, 95% CI = 0.59–1.15); signs of anxiety (SMD = 0.91, 95% CI = 0.56–1.25); signs of depression (SMD = 1.24, 95% CI = 0.98–1.49). It also increased mortality rates (hazard ratio = 1.48, 95% CI = 1.25–1.74; relative median survival = 0.91, 95% CI = 0.89–0.94). Meta-regressions indicated that such housing effects were ubiquitous across species and sexes, but could not identify the most impactful improvements to conventional housing. Data variability (assessed via coefficient of variation) was also not increased by ‘enriched’ housing. Conclusions Conventional housing appears sufficiently distressing to compromise rodent health, raising ethical concerns. Results also add to previous work to show that research rodents are typically CRAMPED (cold, rotund, abnormal, male-biased, poorly surviving, enclosed and distressed), raising questions about the validity and generalisability of the data they generate. This research was funded by NSERC, Canada.

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Long-Term and Short-Term Prognostic Value of Circulating Soluble Suppression of Tumorigenicity-2 Concentration in Chronic Heart Failure: A Systematic Review and Meta-Analysis

Cardiology ◽

10.1159/000509660 ◽

2021 ◽

pp. 1-8

Author(s):

Guoqi Dong ◽

Hao Chen ◽

Hongru Zhang ◽

Yihuang Gu

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Prognostic Value ◽

Web Of Science ◽

Meta Analysis ◽

Short Term ◽

Prisma Statement ◽

All Cause Mortality ◽

Increasing Risk

Introduction: Soluble suppression of tumorigenicity-2 (sST2) has been considered as a prognostic factor of cardiovascular disease. However, the prognostic value of sST2 concentration in chronic heart failure remains to be summarized. Methods: We searched PubMed, Embase, and Web of Science for eligible studies up to January 1, 2020. Data extracted from articles and provided by authors were used in agreement with the PRISMA statement. The endpoints were all-cause mortality (ACM), cardiovascular mortality (CVM)/heart failure-related hospitalization (HFH), and all-cause mortality (ACM)/heart failure-related readmission (HFR). Results: A total of 11 studies with 5,121 participants were included in this analysis. Higher concentration of sST2 predicted the incidence of long-term ACM (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.02–1.04), long-term ACM/HFR (HR: 1.42, CI: 1.27–1.59), and long-term CVM/HFH (HR: 2.25, CI: 1.82–2.79), regardless of short-term ACM/HFR (HR: 2.31, CI: 0.71–7.49). Conclusion: Higher sST2 concentration at baseline is associated with increasing risk of long-term ACM, ACM/HFR, and CVM/HFH and can be a tool for the prognosis of chronic heart failure.

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Osteoarthritis, mobility-related comorbidities and mortality: an overview of meta-analyses

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x20981219 ◽

2020 ◽

Vol 12 ◽

pp. 1759720X2098121

Author(s):

Gustavo Constantino de Campos ◽

Raman Mundi ◽

Craig Whittington ◽

Marie-Josée Toutounji ◽

Wilson Ngai ◽

...

Keyword(s):

Diabetes Mellitus ◽

Odds Ratio ◽

Meta Analysis ◽

Inclusion Criteria ◽

Increased Risk ◽

All Cause Mortality ◽

Ischemic Attack ◽

Meta Analyses ◽

The Relationship ◽

Related Mortality

Aims: The objective of this review was to examine the relationship between osteoarthritis (OA) and mobility-related comorbidities, specifically diabetes mellitus (DM) and cardiovascular disease (CVD). It also investigated the relationship between OA and mortality. Methods: An overview of meta-analyses was conducted by performing two targeted searches from inception to June 2020. The association between OA and (i) DM or CVD ( via PubMed and Embase); and (ii) mortality ( via PubMed) was investigated. Meta-analyses were selected if they included studies that examined adults with OA at any site and reported associations between OA and DM, CVD, or mortality. Evidence was synthesized qualitatively. Results: Six meta-analyses met inclusion criteria. One meta-analysis of 20 studies demonstrated a statistically significant association between OA and DM, with pooled odds ratio of 1.41 (95% confidence interval: 1.21, 1.65; n = 1,040,175 patients). One meta-analysis of 15 studies demonstrated significantly increased risk of CVD among OA patients, with a pooled risk ratio of 1.24 (1.12, 1.37, n = 358,944 patients). Stratified by type of CVD, OA was shown to be associated with increased heart failure (HF) and ischemic heart disease (IHD) and reduced transient ischemic attack (TIA). There was no association reported for stroke or myocardial infarction (MI). Three meta-analyses did not find a significant association between OA (any site) and all-cause mortality. However, OA was found to be significantly associated with cardiovascular-related death across two meta-analyses. Conclusion: The identified meta-analyses reported significantly increased risk of both DM and CVD (particularly, HF and IHD) among OA patients. It was not possible to confirm consistent directional or causal relationships. OA was found to be associated with increased mortality, but mostly in relation to CVD-related mortality, suggesting that further study is warranted in this area.

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Surgical Management of Bilateral Vocal Fold Paralysis in Children: A Systematic Review and Meta-analysis

Otolaryngology ◽

10.1177/0194599820944892 ◽

2020 ◽

pp. 019459982094489

Author(s):

Ryan Kendall Thorpe ◽

Sohit Paul Kanotra

Keyword(s):

Vocal Fold ◽

Web Of Science ◽

Surgical Intervention ◽

Meta Analysis ◽

Vocal Fold Paralysis ◽

Cochrane Library ◽

Inclusion Criteria ◽

Initial Management ◽

Bilateral Vocal Fold Paralysis ◽

Meta Analyses

Objectives To examine and compare the outcomes of various types of glottic widening surgery (GWS) for initial management of bilateral vocal fold paralysis (BVFP) in children, the outcomes of different GWS procedures in children who underwent initial tracheostomy, and the rate of decannulation in children who underwent tracheostomy alone versus tracheostomy followed by GWS. Data Sources PubMed, Web of Science, Cochrane Library, and Embase were searched following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses) on September 9, 2019, with no date restriction. Review Methods Articles focusing on GWS or tracheostomy for initial management of BVFP were included. Articles describing patients who received no surgical intervention for BVFP were excluded. Results A total of 5989 articles were reviewed: 67 articles met inclusion criteria, and 240 patients were incorporated into the analysis. Patients who underwent primary GWS had an eventual tracheostomy rate of 6.0% (5/83). There were no statistically significant differences in the rate of tracheostomy, reoperation, or mortality among cricoid split, suture lateralization, and cordectomy/cordotomy. Patients who underwent primary tracheostomy failed to achieve decannulation in 36.9% (58/157) of cases. Decannulation was more likely in tracheostomized children who received GWS than those who did not (odds ratio, 6.336; P < .0001). Conclusions Most children who undergo primary GWS for BVFP avoid tracheostomy or reoperation. These data demonstrated no differences in surgical outcomes among the most common types of GWS for BVFP. For children who receive a tracheostomy as their first intervention for BVFP, GWS is associated with a significantly improved rate of decannulation.

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Impact of Non-Confinement Accommodation on Farrowing Performance: A Systematic Review and Meta-Analysis of Farrowing Crates Versus Pens

Animals ◽

10.3390/ani9110957 ◽

2019 ◽

Vol 9 (11) ◽

pp. 957 ◽

Cited By ~ 1

Author(s):

Dannielle Glencorse ◽

Kate Plush ◽

Susan Hazel ◽

Darryl D’Souza ◽

Michelle Hebart

Keyword(s):

Systematic Review ◽

Relative Risk ◽

Web Of Science ◽

Meta Analysis ◽

Inclusion Criteria ◽

Literature Searches ◽

Piglet Mortality ◽

Partial Confinement ◽

Meta Analyses ◽

Piglet Survival

There are conflicting reports regarding the effect of farrowing house accommodation on piglet performance. The aim of this investigation was to use a systematic review and meta-analyses to summarise the results of publications that focused on direct comparisons between full confinement conventional crates and various designs of loose-housed farrowing pens from loading until weaning. Literature searches in Scopus, BIOSIS Previews, Cab Abstracts, and Web of Science identified 6695 articles. Twenty-two publications were retained for the systematic review and individual meta-analyses after screening for inclusion criteria. The random effects meta-analyses were performed on crate versus pen for number of piglets born alive, number of stillborn piglets, pre-weaning mortality, and number of piglets weaned. Additionally, the modifiers of confinement length (no confinement from loading until weaning or partial confinement for shorter periods of time in the early stages post parturition), enrichment (no enrichment or enrichment provided), and pen size (small, medium, or large) were examined. There was a 14% increase in the relative risk of piglet mortality in farrowing pens when they were compared with crates (p = 0.0015). The number of stillborns per litter was not different between the pen and crate. However, when providing enrichment in the pens, there was an increase in stillborns within farrowing crates versus pens (p = 0.009). There was no overall effect on piglets that were born alive or number weaned. As there is no difference between piglets born alive and mortality is significantly higher in farrowing pens, a reduction in the number of piglets weaned was expected but not observed, which was possibly due to the lack of weaning details provided in the publications. This was the first systematic review and meta-analysis conducted on the performance of farrowing accommodation and identified that farrowing pens do compromise post-natal piglet survival. Future efforts should focus on improving sow comfort in the farrowing crate to maximize both piglet and sow welfare.

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Febuxostat use and risks of CVD events, death from cardiac-cause and all-cause mortality: metaanalysis of randomized controlled trials

The Journal of Rheumatology ◽

10.3899/jrheum.200307 ◽

2020 ◽

pp. jrheum.200307

Author(s):

Hao Deng ◽

Bao Long Zhang ◽

Jin Dong Tong ◽

Xiu Hong Yang ◽

Hui Min Jin

Keyword(s):

Web Of Science ◽

Meta Analysis ◽

Relevant Literature ◽

Controlled Trials ◽

Cochrane Central Register ◽

Inclusion Criteria ◽

Randomized Controlled ◽

Central Register ◽

Increased Risk ◽

All Cause Mortality

Objective To assess whether febuxostat use increases the risk of developing cardiovascular events, death from cardiac-cause and all-cause mortalities. Methods The relevant literature was searched in several databases including the MEDLINE (PubMed, 1 Jan. 1966–29 Feb. 2020), Web of science, EMBASE (1 Jan. 1974–29 Feb. 2020), ClinicalTrials.gov and Cochrane Central Register for Controlled Trials. Manual searches for references cited in the original studies and relevant review articles were also performed. All studies included in this metanalysis were published in English. Results In the end, 20 studies that met our inclusion criteria were included in this meta-analysis. Use of febuxostat was found not to be associated with an increased risk of all-cause mortality (RR = 0.87, 95% CI 0.57–1.32, P =0.507). Also, there was no association between febuxostat use and mortalities arising from cardiovascular diseases (CVD) (RR = 0.84, 95% CI 0.49–1.45, P=0.528). The RR also revealed that febuxostat use was not associated with CVD events (RR = 0.98, 95% CI 0.83–1.16, P =0.827). Furthermore, the likelihood of occurrence of CVD events was found not to be dependent on febuxostat dose (RR = 1.04, 95% CI 0.84–1.30, P =0.723). Conclusion Febuxostat use is not associated with increased risks of all-cause mortality, death from CVD or CVD events. Accordingly, it is a safe drug for the treatment of gout. Systematic review registration: PROSPERO CRD42019131872

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Influence ofDPYDGenetic Polymorphisms on 5-Fluorouracil Toxicities in Patients with Colorectal Cancer: A Meta-Analysis

Gastroenterology Research and Practice ◽

10.1155/2014/827989 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Qiang Li ◽

Ying Liu ◽

Hong-Mei Zhang ◽

Yin-Peng Huang ◽

Tian-Yi Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Genetic Polymorphisms ◽

Web Of Science ◽

Meta Analysis ◽

Dihydropyrimidine Dehydrogenase ◽

Cochrane Library ◽

Inclusion Criteria ◽

Meta Analyses ◽

The Cochrane Library ◽

Stratified Analysis

Our meta-analysis aggregated existing results from relevant studies to comprehensively investigate the correlations between genetic polymorphisms in dihydropyrimidine dehydrogenase (DPYD) gene and 5-fluorouracil (5-FU) toxicities in patients with colorectal cancer (CRC). The MEDLINE (1966∼2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980∼2013), CINAHL (1982∼2013), Web of Science (1945∼2013), and the Chinese Biomedical Database (CBM) (1982∼2013) were searched without language restrictions. Meta-analyses were conducted with the use of STATA software (Version 12.0, Stata Corporation, College Station, TX, USA). Seven clinical cohort studies with a total of 946 CRC patients met our inclusion criteria, and NOS scores of each of the included studies were ≥5. Our findings showed thatDPYDgenetic polymorphisms were significantly correlated with high incidences of 5-FU-related toxicity in CRC patients. SNP-stratified analysis indicated that there were remarkable connections of IVS14+1G>A, 464T>A, and 2194G>A polymorphisms with the incidence of marrow suppression in CRC patients receiving 5-FU chemotherapy. Furthermore, we found that IVS14+1G>A, 496A>G, and 2194G>A polymorphisms were correlated with the incidence of gastrointestinal reaction. Ethnicity-stratified analysis also revealed thatDPYDgenetic polymorphisms might contribute to the development of marrow suppression and gastrointestinal reaction among Asians, but not among Caucasians. The present meta-analysis suggests thatDPYDgenetic polymorphisms may be correlated with the incidence of 5-FU-related toxicity in CRC patients.

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Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis

PLoS Medicine ◽

10.1371/journal.pmed.1003763 ◽

2021 ◽

Vol 18 (9) ◽

pp. e1003763

Author(s):

Kathy Trieu ◽

Saiuj Bhat ◽

Zhaoli Dai ◽

Karin Leander ◽

Bruna Gigante ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Meta Analysis ◽

Fat Intake ◽

Cvd Risk ◽

Dairy Fat ◽

All Cause Mortality ◽

Meta Analyses ◽

Incident Cardiovascular Disease ◽

Swedish Cohort

Background We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality. Methods and findings We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose–response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case–cohort, or nested case–control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. Conclusions In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.

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Prevalence of dementia in long-term care institutions: a meta-analysis

Jornal Brasileiro de Psiquiatria ◽

10.1590/0047-2085000000298 ◽

2021 ◽

Vol 70 (1) ◽

pp. 59-67

Author(s):

Daniel Ferreira Fagundes ◽

Marcos Túlio Costa ◽

Bárbara Bispo da Silva Alves ◽

Maria Madalena Soares Benício ◽

Lanna Pinheiro Vieira ◽

...

Keyword(s):

Quality Of Life ◽

Older Adults ◽

Long Term Care ◽

Web Of Science ◽

Meta Analysis ◽

Term Care ◽

Meta Analyses ◽

Prevalence Of Dementia

ABSTRACT Objective: This study comprises a systematic review and meta-analysis that aimed to estimate the prevalence of dementia in long-term care institutions (LTCIs). Methods: We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Original transversal and longitudinal articles published until July 2020 were eligible in this review. Databases PubMed/MedLine, Web of Science, Scopus and ScienceDirect were searched. Overall prevalence and confidence intervals were estimated. Heterogeneity was calculated according to the index of heterogeneity (I2). Results: One hundred seventy-five studies were found in all databases and 19 studies were meta-analyses, resulting in an overall prevalence of 53% (CI 46-59%; p < 0.01) of demented older adults living in LTCIs. Conclusion: Prevalence of dementia is higher in older adults living in LTCIs than those living in general communities. This data shows a worrying reality that needs to be changed. There is a need for a better understanding of the elements that cause this increase in dementia in LTCFs to direct actions to improve the quality of life and health of institutionalized elderly.

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Serum Urate and the Risk of Parkinson's Disease: Results From a Meta-Analysis

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100012981 ◽

2013 ◽

Vol 40 (1) ◽

pp. 73-79 ◽

Cited By ~ 45

Author(s):

Chunhong Shen ◽

Yi Guo ◽

Wei Luo ◽

Chen Lin ◽

Meiping Ding

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Web Of Science ◽

Meta Analysis ◽

Serum Urate ◽

High Serum ◽

Protective Effects ◽

Inclusion Criteria ◽

Serum Urate Level

Objective:Serum urate may exert protective effects against Parkinson's disease (PD) through its antioxidant capacities. In this article, we examine the hypothesis that high serum urate levels are associated with lower risk of PD.Methods:We searched NCBI (PubMed), ISI Web of Science and EMBASE for studies that reported the risk of PD associated with serum urate. Fixed or random effects meta-analysis was used to pool results across studies, and further analysis was used to assess the effects by gender.Results:Six studies met the inclusion criteria involving a total of 33 185 participants. Overall, we found a 33% reduction in PD incidence among persons with high serum urate level (relative risk [RR]=0.67; 95% confidence interval [CI], 0.50-0.91). Subgroup analysis was performed with 20 641 men and 12 544 women included, indicating statistically significant protective effects of serum urate in men (RR=0.60; 95% CI, 0.40-0.90) but not in women. A dose-response trend of serum urate to reduce PD risk was also observed involving 11 795 participants (RR=0.77; 95% CI, 0.68-0.88). Additionally, high serum urate levels seemed to slow the clinical decline of PD patients (RR=0.56; 95% CI, 0.43-0.72).Conclusions:In light of these findings, our study confirms previous findings of a robust association between high serum urate level and PD risk, especially in men. It also suggests that long-term exposure to high serum urate may be linked to the delay of PD progression, however more well-designed investigations are needed.

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Role of the IL-33/ST2 axis in cardiovascular disease: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0259026 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0259026

Author(s):

Yuan Sun ◽

Holly Pavey ◽

Ian Wilkinson ◽

Marie Fisk

Keyword(s):

Systematic Review ◽

Cardiovascular Disease ◽

Random Effects ◽

Meta Analysis ◽

Coronary Syndrome ◽

Hazard Ratios ◽

All Cause Mortality ◽

Artery Disease ◽

Meta Analyses

Interleukin (IL)-33 and its unique receptor, ST2, play a pivotal role in the immune response to infection and stress. However, there have been conflicting reports of the role of IL-33 in cardiovascular disease (CVD) and the potential of this axis in differentiating CVD patients and controls and with CVD disease severity, remains unclear. Aims 1) To quantify differences in circulating IL-33 and/or sST2 levels between CVD patients versus controls. 2) Determine association of these biomarkers with mortality in CVD and community cohorts. Methods and results Using Pubmed/MEDLINE, Web of Science, Prospero and Cochrane databases, systematic review of studies published on IL-33 and/or sST2 levels in patients with CVD (heart failure, acute coronary syndrome, atrial fibrillation, stroke, coronary artery disease and hypertension) vs controls, and in cohorts of each CVD subtype was performed. Pooled standardised mean difference (SMD) of biomarker levels between CVD-cases versus controls and hazard ratios (HRs) for risk of mortality during follow-up in CVD patients, were assessed by random effects meta-analyses. Heterogeneity was evaluated with random-effects meta-regressions. From 1071 studies screened, 77 were meta-analysed. IL-33 levels were lower in HF and CAD patients vs controls, however levels were higher in stroke patients compared controls [Meta-SMD 1.455, 95% CI 0.372–2.537; p = 0.008, I2 = 97.645]. Soluble ST2 had a stronger association with risk of all-cause mortality in ACS (Meta-multivariate HR 2.207, 95% CI 1.160–4.198; p = 0.016, I2 = 95.661) than risk of all-cause mortality in HF (Meta-multivariate HR 1.425, 95% CI 1.268–1.601; p<0.0001, I2 = 92.276). There were insufficient data to examine the association of IL-33 with clinical outcomes in CVD. Conclusions IL-33 and sST2 levels differ between CVD patients and controls. Higher levels of sST2 are associated with increased mortality in individuals with CVD. Further study of IL-33/ST2 in cardiovascular studies is essential to progress diagnostic and therapeutic advances related to IL-33/ST2 signalling.

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