Bacteriophage ISP eliminates Staphylococcus aureus in planktonic phase, but not in the various stages of the biofilm cycle.

Metal-implant associated bacterial infections are a major clinical problem due to antibiotic treatment failure. As an alternative, we determined the effects of bacteriophage ISP on clinical isolates of Staphylococcus aureus in various stages of its life cycle in relation to biofilm formation and maturation. ISP effectively eliminated all planktonic phase bacteria, whereas its efficacy was reduced against bacteria attached to the metal implant and bacteria embedded within biofilms. The biofilm architecture hampered the bactericidal effects of ISP, as mechanical disruption of biofilms improved the efficacy of ISP against the bacteria. Phages penetrated the biofilm and interacted with the bacteria throughout the biofilm. However, most of the biofilm-embedded bacteria were phage-tolerant. In agreement, bacteria dispersed from mature biofilms of all clinical isolates, except for LUH15394, tolerated the lytic activity of ISP. Lastly, persisters within mature biofilms tolerated ISP and proliferated in its presence. Based on these findings, we conclude that ISP eliminates planktonic phase Staphylococcus aureus while its efficacy is limited against bacteria attached to the metal implant, embedded within (persister-enriched) biofilms, and dispersed from biofilms.

Technology assistance in primary total knee replacement: hype or hope?

INTRODUCTION: Total knee replacement (TKR) reduces pain, it increases quality of life and it generally lasts a long time with revision rates of less than 5% at 10 years. Some authors have suggested that outcomes may be further improved by technology assistance. AREAS COVERED: Technology assistance in primary TKR includes technologies such as navigated TKR, patient specific instrumentation TKR and robotic TKR. EXPERT OPINION: In general, technology assistance results in higher accuracy of component positioning and alignment, but this is likely not clinically relevant as no clinically important difference in clinical outcomes, quality of life and complications such as revisions has been demonstrated in meta-analyses of randomized controlled trials. As technology assistance in primary TKR is increasingly used to capture patient and surgeon data, surgeons have an increasingly important role in protecting their patients' data and their own data. Real world evidence of implant registries has shown that TKR without technologically assistance can achieve perfectly acceptable outcomes. Although there is a genuine hope that technology-assisted TKR may further improve these outcomes, this hope is based on promises rather than solid evidence. At the same time, technology assisted TKR is heavily promoted including direct patient marketing, which are aspects of a hype.

Machine Learning assisted systematic reviewing in orthopaedics.

Background: Machine learning assisted systematic reviewing may help to reduce the work burden in systematic reviews. The aim of this study is therefore to determine by a non-developer the performance of machine learning assisted systematic reviewing on previously published orthopaedic reviews in retrieving relevant papers. Methods: Active learning for Systematic Reviews (ASReview) was tested against the results from three previously published systematic reviews in the field of orthopaedics with 20 iterations for each review. The reviews covered easy, intermediate and advanced scenarios. The outcomes of interest were the percentage work saved at 95% recall (WSS@95), the percentage work saved at 100% recall (WSS@100) and the percentage of relevant references identified after having screened the first 10% of the records (RRF@10). Means and corresponding [95% confidence intervals] were calculated. Results: The WSS@95 was respectively 72 [71-74], 72 [72-73] and 50 [50-51] for the easy, intermediate and advanced scenarios. The WSS@100 was respectively 72 [71-73], 62 [61-63] and 37 [36-38] for the easy, intermediate and advanced scenarios. The RRF@10 was respectively 79 [78-81], 70 [69-71] and 58 [56-60] for the easy, intermediate and advanced scenarios. Conclusions: Machine learning assisted systematic reviewing was efficient in retrieving relevant papers for systematic review in orthopaedics. The majority of relevant papers were identified after screening only 10% of the papers. All relevant papers were identified after screening 30%-40% of the total papers meaning that 60%-70% of the work can potentially be saved.

Increased risk of aseptic loosening for posterior stabilized compared with posterior cruciate-retaining uncemented total knee replacements: a cohort study of 13,667 knees from the Dutch Arthroplasty Registry.

BACKGROUND AND PURPOSE: While registry studies have suggested a higher risk of revision for posterior-stabilized (PS) compared with posterior cruciate-retaining (CR) total knee replacements (TKR) using cement, it is unknown whether this is also the case for uncemented TKR. We aimed to compare the revision rates of PS and CR designs in patients receiving primary uncemented TKR. PATIENTS AND METHODS: Data from the Dutch arthroplasty register (LROI) was analyzed, comprising 12,226 uncemented primary CR TKRs and 750 uncemented PS TKRs registered between 2007 and 2022. Competing risk and multivariable Cox regression analyses were used to compare revision rates, risks of revision, and reasons for revision between groups. Sensitivity analyses were performed to analyze the risk, concerning the 5 most commonly used implants and performing hospitals for each group. RESULTS: Uncemented PS TKRs had higher 10-year revision rates for any reason and aseptic loosening (6.5%, 95% confidence interval [CI] 4.6-9.2 and 3.9%, CI 2.6-6.7) compared with uncemented CR TKRs (4.2%, CI 3.8-4.7 and 1.4%, CI 1.2-1.7). PS TKRs were 1.4 and 2.5 times more likely to be revised for any reason and aseptic loosening, respectively. These results remained consistent after adjustment for age, sex, BMI, previous surgeries, bearing mobility, and surface modification, with sensitivity analyses. CONCLUSION: We found that uncemented PS implants have a higher rate of revision than uncemented CR implants, mainly due to a higher risk of aseptic loosening.

6-month migration sufficient for evaluation of total knee replacements: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This updated meta-analysis evaluates the migration pattern of the tibial component of primary total knee replacements measured with radiostereometric analysis (RSA). We aimed to evaluate whether 6-month maximum total point motion (MTPM) values could be used instead of 1-year MTPM for RSA threshold testing and to present the pooled migration patterns for different implant designs that can be used as a benchmark. PATIENTS AND METHODS: The search included all published RSA studies on migration patterns of tibial components until 2023. Study groups were classified according to their prosthesis brand, fixation, and insert (PFI). Sub-analyses were performed to compare the mean tibial component migration patterns of different implant variables, stratified according to fixation. RESULTS: 96 studies (43 new studies), including 197 study groups and 4,706 knees, were included. Most migration occurred within the first 6 postoperative months (126 study groups: mean 0.58 mm, 95% confidence interval [CI] 0.50-0.65), followed by minimal migration between 6 and 12 months (197 study groups: mean 0.04 mm, CI 0.03-0.06), irrespective of the fixation method used. Distinct migration patterns were observed among the different fixation methods. No differences were found in migration patterns among cemented components in any of the sub-group analyses conducted. For uncemented implants, trabecular metal surfaced components seemed to migrate less than porous-coated or uncoated components Conclusion: Based on the small difference between MTPM values at 6 months and 1 year, MTPM at 6 months could be used instead of MTPM at 1 year for RSA threshold testing. The pooled migration patterns can be used as benchmark for evaluation of new implants by defining fixation-specific RSA thresholds when combined with implant survival.

Migration patterns of acetabular cups: a systematic review and meta-analysis of RSA studies.

BACKGROUND AND PURPOSE: We conducted a systematic review and meta-analysis of RSA studies to investigate the early and long-term migration patterns of acetabular cups and the influence of implant factors on cup migration over time. METHODS: We performed a systematic search of PubMed, Embase, and Scopus databases to identify all RSA studies of cup migration following primary total hip replacement (THR). Proximal migration at 3 and 6 months, 1, 2, 5, and 10 years were considered for analysis. Implant factors investigated included fixation type, head size, bearing surface, uncemented coating design, and the decade of RSA introduction. RESULTS: 47 studies reported the proximal migration of 83 cohorts (2,328 cups). Besides 1 threaded cup design, no implant factor investigated was found to significantly influence proximal migration. The mean pooled 2-year proximal migration of cemented cups (0.14 mm, 95% confidence interval [CI] 0.08-0.20) was not significantly different from uncemented cups (0.12 mm, CI 0.04-0.19). The mean pooled proximal migration at 6 months was 0.11 mm (CI 0.06-0.16) and there was no significant increase between 6 months and 2 years (0.015 mm, CI 0.000-0.030). 27 of 75 cohorts (36%) reported mean proximal migration greater than 0.2 mm at 2 years, which has previously been identified as a predictor of implants at risk of long-term loosening. CONCLUSION: Our meta-analysis demonstrated that the majority of cup migration occurs within the first 6 months. With one exception, no implant factors influenced the 2-year proximal migration of acetabular cups. 36% of studies with 2-year migration were considered at risk of long-term loosening. Further investigation and comparison against long-term survivorship data would validate 6-month and/or 1-year proximal migration measurements as an earlier predictor of long-term loosening than the current 2-year threshold.

Antimicrobial activity of ion-substituted calcium phosphates: A systematic review.

In this systematic review, the antimicrobial effect of ion-substituted calcium phosphate biomaterials was quantitatively assessed. The literature was systematically searched up to the 6th of December 2021. Study selection and data extraction was performed in duplo by two independent reviewers with a modified version of the OHAT tool for risk of bias assessment. Any differences were resolved by consensus or by a referee. A mixed effects model was used to investigate the relation between the degree of ionic substitution and bacterial reduction. Of 1016 identified studies, 108 were included in the analysis. The methodological quality of included studies ranged from 6 to 16 out of 18 (average 11.4). Selenite, copper, zinc, rubidium, gadolinium, silver and samarium had a clear antimicrobial effect, with a log reduction in bacteria count of 0.23, 1.8, 2.1, 3.6, 5.8, 7.4 and 10 per atomic% of substitution, respectively. There was considerable between-study variation, which could partially be explained by differences in material formulation, study quality and microbial strain. Future research should focus on clinically relevant scenarios in vitro and the translation to in vivo prevention of PJI.

Influence of surface characteristics of implant materials on MRSA biofilm formation and effects of antimicrobial treatment.

Introduction: One of the main causes of treatment failure in bacterial prosthetic joint infections (PJI) is biofilm formation. The topography of the biofilm may be associated with susceptibility to antimicrobial treatment. The aims of this study were to assess differences in topography of biofilms on different implant materials and the correlation thereof with susceptibility to antimicrobial treatment. Methods: Methicillin-resistant Staphylococcus aureus (MRSA) 7-day mature biofilms were generated on disks made from titanium alloys (Ti-6Al-7Nb and Ti-6Al-4V), synthetic polymer and orthopedic bone cement, commonly used in implant surgery. The surface topography of these implant materials and the biofilms cultured on them was assessed using atomic force microscopy. This provided detailed images, as well as average roughness (Ra) and peak-to-valley roughness (Rt) values in nanometers, of the biofilm and the material surfaces. Bacterial counts within biofilms were assessed microbiologically. Antimicrobial treatment of biofilms was performed by 24-h exposure to the combination of rifampicin and ciprofloxacin in concentrations of 1-, 5- and 10-times the minimal bactericidal concentration (MBC). Finally, treatment-induced differences in bacterial loads and their correlation with biofilm surface parameters were assessed. Results: The biofilm surfaces on titanium alloys Ti-6Al-7Nb (Ra = 186 nm) and Ti-6Al-4V (Ra = 270 nm) were less rough than those of biofilms on silicone (Ra = 636 nm). The highest roughness was observed for biofilms on orthopedic bone cement with an Ra of 1,551 nm. Interestingly, the roughness parameters of the titanium alloys themselves were lower than the value for silicone, whereas the surface of the bone cement was the roughest. Treatment with 1- and 5-times the MBC of antibiotics resulted in inter-material differences in colony forming units (CFU) counts, ultimately showing comparable reductions of 2.4-3.0 log CFU/mL at the highest tested concentration. No significant differences in bacterial loads within MRSA biofilms were observed between the various implant materials, upon exposure to increasing concentrations of antibiotics. Discussion: The surface parameters of MRSA biofilms were determined by those of the implant materials on which they were formed. The antibiotic susceptibility of MRSA biofilms on the various tested implant materials did not differ, indicating that the efficacy of antibiotics was not affected by the roughness of the biofilm.

Change in CT-measured acetabular bone density following total hip arthroplasty: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Assessing peri-acetabular bone quality is valuable for optimizing the outcomes of primary total hip arthroplasty (THA) as preservation of good quality bone stock likely affects implant stability. The aim of this study was to perform a meta-analysis of peri-acetabular bone mineral density (BMD) changes over time measured using quantitative computer tomography (CT) and, second, to investigate the influence of age, sex, and fixation on the change in BMD over time. METHODS: A systematic search of Embase, Scopus, Web of Science, and PubMed databases identified 19 studies that measured BMD using CT following THA. The regions of interest (ROI), reporting of BMD results, and scan protocols were extracted. A meta-analysis of BMD was performed on 12 studies that reported measurements immediately postoperatively and at follow-up. RESULTS: The meta-analysis determined that periacetabular BMD around both cemented and uncemented components decreases over time. The amount of BMD loss increased relative to proximity of the acetabular component. There was a greater decrease in cortical BMD over time in females and cancellous BMD for young patients of any sex. CONCLUSION: Peri-acetabular BMD decreases at different rates relative to its proximity to the acetabular component. Cancellous BMD decreases more in young patients and cortical bone decreases more in females. Standardized reporting parameters and suggested ROI to measure peri-acetabular BMD are proposed, to enable comparison between implant and patient variables in the future.

Five-year migration and insert wear of uncemented tibial components with either conventional polyethylene or sequentially annealed highly crosslinked polyethylene inserts: a blinded randomized controlled trial using radiostereometric analysis.

The primary objective of this study was to compare the five-year tibial component migration and wear between highly crosslinked polyethylene (HXLPE) inserts and conventional polyethylene (PE) inserts of the uncemented Triathlon fixed insert cruciate-retaining total knee arthroplasty (TKA). Secondary objectives included clinical outcomes and patient-reported outcome measures (PROMs). A double-blinded, randomized study was conducted including 96 TKAs. Tibial component migration and insert wear were measured with radiostereometric analysis (RSA) at three, six, 12, 24, and 60 months postoperatively. PROMS were collected preoperatively and at all follow-up timepoints. There was no clinically relevant difference in terms of tibial component migration, insert wear, and PROMs between the HXLPE and PE groups. The mean difference in tibial component migration (maximal total point migration (MTPM)) was 0.02 mm (95% confidence interval (CI) -0.07 to 0.11), which is below the value of 0.2 mm considered to be clinically relevant. Wear after five years for HXLPE was 0.16 mm (95% CI 0.05 to 0.27), and for PE was 0.23 mm (95% CI 0.12 to 0.35). The mean difference in wear rate was 0.01 mm/year (95% CI -0.02 to 0.05) in favour of the HXLPE group. Wear is mainly present on the medial side of the insert. There is no clinically relevant difference in tibial component migration and insert wear for up to five years between the HXLPE conventional PE inserts. For the implant studied, the potential advantages of a HXLPE insert remain to be proven under clinical conditions at longer-term follow-up.

A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses : a proof of principle study.

AIMS: Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (99mTc-UBI29-41-Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods. METHODS: 99mTc-UBI29-41-Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria. RESULTS: Bacteria could be effectively stained in vitro and on prostheses, irrespective of the presence of biofilm. Infected prostheses revealed bacterial presence on the transition zone between the head and neck, and in the screw hole. Qualitative 2D fluorescence images could be complemented with quantitative 3D fhSPECT scans. Despite thorough chlorhexidine treatments, 28% to 44% of the signal remained present in the locations of the infection that were identified using imaging, which included 500 to 2,000 viable bacteria. CONCLUSION: The hybrid tracer 99mTc-UBI29-41-Cy5 allowed effective bacterial staining. Qualitative real-time fluorescence guidance could be effectively combined with nuclear imaging that enables quantitative monitoring of the effectiveness of cleaning strategies.Cite this article: Bone Joint Res 2023;12(1):72-79.

RSA migration of unicondylar knee arthroplasties is comparable to migration of total knee arthroplasties: A meta-analysis.

IMPORTANCE: Aseptic loosening is a major cause of failure for unicondylar knee arthroplasty (UKA). In total knee arthroplasty (TKA), early migration as measured with radiostereometric analysis (RSA) is a strong predictor of late revision for aseptic loosening of the tibial component. Migration in the first two years provides information on the fixation of an implant. However, the migration pattern of UKAs has not been systematically determined, and it is unclear if the migration pattern of UKAs is similar to that of TKAs. Therefore, the present meta-analysis aims to evaluate the migration patterns of tibial components of UKAs. EVIDENCE REVIEW: All RSA studies reporting on migration at two or more postoperative time-points following UKA were included. Pubmed, Web of Science, Cochrane, and Embase were searched up to April 2021. The risk of bias was assessed using the methodological score of the Assessment of Quality in Lower Limb Arthroplasty tool. All phases of the review were performed by two reviewers independently. A random-effects model was applied to pool the migration data. FINDINGS: The literature search yielded 3,187 hits, of which ten studies were included, comprising 13 study groups and 381 UKAs. The majority of the early migration occurred in the first 6 months postoperatively followed by a period of very little migration, similar to what is reported for TKAs. The pooled mean migration expressed as the maximum total point motion of all UKAs at 3 months, 6 months, 1 year, and 2 years was 0.43 mm (95% CI 0.38-0.48), 0.54 mm (95% CI 0.40-0.67), 0.59 mm (95% CI 0.52-0.66), and 0.61 mm (95% CI 0.55-0.68), respectively. Migration at one year and two years was higher than migration of TKAs as reported in previous studies. All-polyethylene UKAs migrated more at one year (0.69 mm; 95% CI 0.58-0.80) than metal-backed UKAs (0.52 mm; 95% CI 0.46-0.58). CONCLUSIONS AND RELEVANCE: The migration pattern of UKAs is comparable with that of TKAs in the first two years as both types of implants show initial migration in the first few months and very little migration thereafter. However, UKAs had higher migration at 1-year and 2-year follow-up.

Temporal trends of sex differences for COVID-19 infection, hospitalisation, severe disease, intensive care unit (ICU) admission and death: a meta-analysis of 229 studies covering over 10M patients.

Background: This review aims to investigate the association of sex with the risk of multiple COVID-19 health outcomes, ranging from infection to death. Methods: Pubmed and Embase were searched through September 2020. We considered studies reporting sex and coronavirus disease 2019 (COVID-19) outcomes. Qualitative and quantitative data were extracted using standardised electronic data extraction forms with the assessment of Newcastle Ottawa Scale for risk of bias. Pooled trends in infection, hospitalization, severity, intensive care unit (ICU) admission and death rate were calculated separately for men and women and subsequently random-effects meta-analyses on relative risks (RR) for sex was performed. Results: Of 10,160 titles, 229 studies comprising 10,417,452 patients were included in the analyses. Methodological quality of the included studies was high (6.9 out of 9). Men had a higher risk for infection with COVID-19 than women (RR = 1.14, 95%CI: 1.07 to 1.21). When infected, they also had a higher risk for hospitalization (RR = 1.33, 95%CI: 1.27 to 1.41), higher risk for severe COVID-19 (RR = 1.22, 95%CI: 1.17 to 1.27), higher need for Intensive Care (RR = 1.41, 95%CI: 1.28 to 1.55), and higher risk of death (RR = 1.35, 95%CI: 1.28 to 1.43). Within the period studied, the RR for infection and severity increased for men compared to women, while the RR for mortality decreased for men compared to women. Conclusions: Meta-analyses on 229 studies comprising over 10 million patients showed that men have a higher risk for COVID-19 infection, hospitalization, disease severity, ICU admission and death. The relative risks of infection, disease severity and death for men versus women showed temporal trends with lower relative risks for infection and severity of disease and higher relative risk for death at the beginning of the pandemic compared to the end of our inclusion period. PROSPERO registration: CRD42020180085 (20/04/2020).

Inhaled Corticosteroids, Vitamin K Antagonists and Amlodipine Were Associated with an Increased Risk of Acute Periprosthetic Joint Infection in Patients with Total Hip Arthroplasty: A Retrospective Case-Cohort Study.

The perioperative use of certain medication may influence the risk of developing a periprosthetic joint infection (PJI). Inhaled corticosteroids (ICSs) and cardiovascular drugs are widely used against pulmonary and cardiovascular diseases. While oral corticosteroids and anticoagulants have been shown to increase the risk of developing PJI, this is not clear for ICSs. In contrast, some cardiovascular drugs, such as amlodipine, nifedipine and statins, have been documented to show an antimicrobial effect, suggesting a synergistic effect with antibiotics in the treatment of (multi-resistant) microorganisms. We performed a case-cohort study to assess the association between the occurrence of PJI after THA and the use of inhaled corticosteroids, anticoagulants, or previously mentioned cardiovascular agents. In a cohort of 5512 primary THAs, we identified 75 patients with a PJI (1.4%), and randomly selected 302 controls. A weighted Cox proportional hazard regression model was used for the study design and to adjust for potential confounders (age, sex, smoking, and cardiovascular/pulmonary disease). We found ICS use (HR 2.6 [95% CI 1.1-5.9]), vitamin K antagonist use (HR 5.3 [95% CI 2.5-11]), and amlodipine use (HR 3.1 [95% CI 1.4-6.9]) to be associated with an increased risk of developing PJI after THA. The effect remained after correction for the mentioned possible confounders. The underlying diseases for which the medications are prescribed could also play a role in the mentioned association; we believe, however, that the usages of ICSs, vitamin K antagonists and amlodipine appear to be potential modifiable risk factors for PJI, and therefore have to be questioned during preoperative screening and consultation.

Decreased mortality and increased side effects in COVID-19 patients treated with IL-6 receptor antagonists: systematic review and meta-analysis.

There is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.

Proton-pump inhibitors are associated with increased risk of prosthetic joint infection in patients with total hip arthroplasty: a case-cohort study.

Background and purpose - Proton-pump inhibitors (PPI) have previously been associated with an increased risk of infections such as community-acquired pneumonia, gastrointestinal infections and central nervous system infection. Therefore, we evaluated a possible association between proton-pump inhibitor use and prosthetic joint infection (PJI) in patients with total hip arthroplasty (THA), because they can be stopped perioperatively or switched to a less harmful alternative.Patients and methods - A cohort of 5,512 primary THAs provided the base for a case-cohort design; cases were identified as patients with early-onset PJI. A weighted Cox proportional hazard regression model was used for the study design and to adjust for potential confounders.Results - There were 75 patients diagnosed with PJI of whom 32 (43%) used PPIs perioperatively compared with 75 PPI users (25%) in the control group of 302 patients. The risk of PJI was 2.4 times higher (95% CI 1.4-4.0) for patients using PPI. This effect remained after correction for possible confounders.Interpretation - The use of PPIs was associated with an increased risk of developing PJI after THA. Hence, the use of a PPI appears to be a modifiable risk factor for PJI.

Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies.

OBJECTIVE: We aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed and Embase through 4 May 2020. STUDY SELECTION: We considered cohort and case-control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death. DATA EXTRACTION AND SYNTHESIS: We screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale. RESULTS: We screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years. CONCLUSIONS: Meta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death. PROSPERO REGISTRATION NUMBER: CRD42020180085.