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BMC Surgery May 2020Despite being a preventable complication of surgical procedures, surgical site infections (SSIs) continue to threaten public health with significant impacts on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite being a preventable complication of surgical procedures, surgical site infections (SSIs) continue to threaten public health with significant impacts on the patients and the health-care human and financial resources. With millions affected globally, there is significant variation in the primary studies on the prevalence of SSIs in Ethiopia. Therefore, this study aimed to estimate the pooled prevalence of SSI and its associated factors among postoperative patients in Ethiopia.
METHODS
PubMed, Scopus, Psyinfo, African Journals Online, and Google Scholar were searched for studies that looked at SSI in postoperative patients. A funnel plot and Egger's regression test were used to determine publication bias. The I statistic was used to check heterogeneity between the studies. DerSimonian and Laird random-effects model was applied to estimate the pooled effect size, odds ratios (ORs), and 95% confidence interval (CIs) across studies. The subgroup analysis was conducted by region, sample size, and year of publication. Sensitivity analysis was deployed to determine the effect of a single study on the overall estimation. Analysis was done using STATA™ Version 14 software.
RESULT
A total of 24 studies with 13,136 study participants were included in this study. The estimated pooled prevalence of SSI in Ethiopia was 12.3% (95% CI: 10.19, 14.42). Duration of surgery > 1 h (AOR = 1.78; 95% CI: 1.08-2.94), diabetes mellitus (AOR = 3.25; 95% CI: 1.51-6.99), American Society of Anaesthesiologists score > 1 (AOR = 2.51; 95% CI: 1.07-5.91), previous surgery (AOR = 2.5; 95% CI: 1.77-3.53), clean-contaminated wound (AOR = 2.15; 95% CI: 1.52-3.04), and preoperative hospital stay > 7 day (AOR = 5.76; 95% CI: 1.15-28.86), were significantly associated with SSI.
CONCLUSION
The prevalence of SSI among postoperative patients in Ethiopia remains high with a pooled prevalence of 12.3% in 24 extracted studies. Therefore, situation based interventions and region context-specific preventive strategies should be developed to reduce the prevalence of SSI among postoperative patients.
Topics: Ethiopia; Humans; Odds Ratio; Prevalence; Risk Factors; Surgical Wound Infection
PubMed: 32423397
DOI: 10.1186/s12893-020-00764-1 -
International Journal of Nursing Studies Apr 2023There is some evidence to suggest that discharge education may reduce the risk of postoperative complications, however, a critical evaluation of the body of evidence is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is some evidence to suggest that discharge education may reduce the risk of postoperative complications, however, a critical evaluation of the body of evidence is needed.
OBJECTIVE
To assess the effect of discharge education interventions versus standard education given to general surgery patients prior to, or up to 30-days of hospital discharge on clinical and patient-reported outcomes.
DESIGN
Systematic review and meta-analysis. Clinical outcomes were 30-day surgical site infection incidence and re-admission up to 28 days. Patient-reported outcomes included patient knowledge, self-confidence, satisfaction, and quality of life.
SETTING
Participants were recruited from hospitals.
PARTICIPANTS
Adult general surgical patients.
METHODS
MEDLINE (Pubmed), CINAHL (EBSCO), EMBASE (Elsevier) and the Cochrane Library were searched in February 2022. Randomised controlled trials and non-randomised studies of interventions published between 2010 and 2022, with adults undergoing general surgical procedures receiving discharge education on surgical recovery, including wound management, were eligible for inclusion. Quality appraisal was undertaken using the Cochrane Risk of Bias 2 and the Risk of Bias Assessment Tool for Nonrandomised Studies. The Grading of Assessment, Development, Recommendations, and Evaluation was used to assess the certainty of the body of evidence based on the outcomes of interest.
RESULTS
Ten eligible studies (eight randomised control trials and two non-randomised studies of interventions) with 965 patients were included. Six randomised control trials assessed the effect of discharge education interventions on 28-day readmission (Odds ratio 0.88, 95 % confidence interval 0.56-1.38). Two randomised control trials assessed the effect of discharge education interventions on surgical site infection incidence (Odds ratio = 0.84, 95 % confidence interval 0.39-1.82). The results of the non-randomised studies of interventions were not pooled due to heterogeneity in outcome measures. The risk of bias was either moderate or high for all outcomes, and the body of evidence using GRADE was judged as very low for all outcomes studied.
CONCLUSIONS
The impact of discharge education on the clinical and patient-reported outcomes of patients undergoing general surgery cannot be determined due to the uncertainty of the evidence base. Despite the increased use of web-based interventions to deliver discharge education to general surgery patients, larger samples in more rigorous multicentre randomised control trials with parallel process evaluations are needed to better understand the effect of discharge education on clinical and patient-reported outcomes.
REGISTRATION
PROSPERO CRD42021285392.
TWEETABLE ABSTRACT
Discharge education may reduce the likelihood of surgical site infection and hospital readmission but the body of evidence is inconclusive.
Topics: Adult; Humans; Surgical Wound Infection; Patient Discharge; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36871540
DOI: 10.1016/j.ijnurstu.2023.104471 -
BJS Open Feb 2019The use of peritoneal lavage to prevent postoperative intra-abdominal abscess (IAA) after appendicectomy has been debated widely. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of peritoneal lavage to prevent postoperative intra-abdominal abscess (IAA) after appendicectomy has been debated widely.
METHODS
A systematic review and meta-analysis of suction alone lavage for appendicitis was performed to determine the relative benefit of lavage. Primary outcomes were postoperative IAA and wound infection (WI). Inclusion criteria were human studies reporting a comparison of appendicectomy with or without peritoneal lavage.
RESULTS
Eight studies met the inclusion criteria, the majority of which were retrospective. Only three were RCTs. Four studies included analysis only of the paediatric population. The rate of IAA was 1·0-19·5 per cent in patients receiving suction alone and 1·5-18·6 per cent in those having lavage. WI rates were 1·0-29·2 per cent for suction alone and 0·8-20·5 per cent for lavage. The pooled risk difference for IAA was 0·01 (95 per cent c.i. -0·03 to 0·06; = 0·50) and that for WI was 0·00 (-0·05 to 0·05; = 0·98). Analyses of both outcomes indicated a medium degree of heterogeneity between effect estimates with values of 71 per cent ( = 0·001) and 70 per cent ( = 0·010) for IAA and WI respectively.
CONCLUSION
There is no evidence of benefit of lavage over suction for postoperative infective complications, and no individual study demonstrated a significant benefit in patients receiving lavage.
Topics: Abdominal Abscess; Acute Disease; Appendectomy; Appendicitis; Humans; Intraoperative Care; Peritoneal Lavage; Postoperative Complications; Suction; Surgical Wound Infection
PubMed: 30734012
DOI: 10.1002/bjs5.50118 -
Journal of ISAKOS : Joint Disorders &... Feb 2024Early periprosthetic joint infection (PJI) represents one of the most fearsome complications of joint replacement. No international consensus has been reached regarding... (Review)
Review
PURPOSE
Early periprosthetic joint infection (PJI) represents one of the most fearsome complications of joint replacement. No international consensus has been reached regarding the best approach for early prosthetic knee and hip infections. The aim of this updated systematic review is to assess whether debridement, antibiotics, and implant retention (DAIR) is an effective choice of treatment in early postoperative and acute hematogenous PJI.
METHODS
This systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The diagnostic criteria defining a PJI, the most present pathogen, and the days between the index procedure and the onset of the PJI were extracted from the selected articles. Additionally, the mean follow-up, antibiotic regimen, and success rate of the treatment were also reported.
RESULTS
The articles included provided a cohort of 970 patients. Ten studies specified the joint of their cohort in PJIs regarding either hip prostheses or knee prostheses, resulting in 454 total knees and 460 total hips. The age of the patients ranged from 18 to 92 years old. Success rates for the DAIR treatments in the following cohort ranged from 55.5% up to a maximum of 90% (mean value of 71%).
CONCLUSION
Even though the DAIR procedure is quite limited, it is still considered an effective option for patients developing an early post-operative or acute hematogenous PJI. However, there is a lack of studies, in particular randomized control trials (RCTs), comparing DAIR with one-stage and two-stage revision protocols in the setting of early PJIs, reflecting the necessity to conduct further high-quality studies to face the burden of early PJI.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Debridement; Anti-Bacterial Agents; Retrospective Studies; Treatment Outcome; Prosthesis-Related Infections; Arthroplasty, Replacement, Hip; Arthritis, Infectious
PubMed: 37714518
DOI: 10.1016/j.jisako.2023.09.003 -
Journal of Dentistry Dec 2014To test the null hypothesis of no difference in the implant failure rates, postoperative infection, and marginal bone loss for the insertion of dental implants in... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
To test the null hypothesis of no difference in the implant failure rates, postoperative infection, and marginal bone loss for the insertion of dental implants in periodontally compromised patients (PCPs) compared to the insertion in periodontally healthy patients (PHPs), against the alternative hypothesis of a difference.
METHODS
An electronic search without time or language restrictions was undertaken in March 2014. Eligibility criteria included clinical human studies, either randomized or not.
RESULTS
2768 studies were identified in the search strategy and 22 studies were included. The estimates of relative effect were expressed in risk ratio (RR) and mean difference (MD) in millimetres. All studies were judged to be at high risk of bias, none were randomized. A total of 10,927 dental implants were inserted in PCPs (587 failures; 5.37%), and 5881 implants in PHPs (226 failures; 3.84%). The difference between the patients significantly affected the implant failure rates (RR 1.78, 95% CI 1.50-2.11; P<0.00001), also observed when only the controlled clinical trials were pooled (RR 1.97, 95% CI 1.38-2.80; P=0.0002). There were significant effects of dental implants inserted in PCPs on the occurrence of postoperative infections (RR 3.24, 95% CI 1.69-6.21; P=0.0004) and in marginal bone loss (MD 0.60, 95% CI 0.33-0.87; P<0.0001) when compared to PHPs.
CONCLUSIONS
The present study suggests that an increased susceptibility for periodontitis may also translate to an increased susceptibility for implant loss, loss of supporting bone, and postoperative infection. The results should be interpreted with caution due to the presence of uncontrolled confounding factors in the included studies, none of them randomized.
CLINICAL SIGNIFICANCE
There is some evidence that patients treated for periodontitis may experience more implant loss and complications around implants including higher bone loss and peri-implantitis than non-periodontitis patients. As the philosophies of treatment may alter over time, a periodic review of the different concepts is necessary to refine techniques and eliminate unnecessary procedures. This would form a basis for optimum treatment.
Topics: Alveolar Bone Loss; Dental Implants; Dental Restoration Failure; Humans; Odds Ratio; Periodontal Diseases; Periodontitis; Periodontium; Surgical Wound Infection
PubMed: 25283479
DOI: 10.1016/j.jdent.2014.09.013 -
Annals of Vascular Surgery Feb 2022The aim of our systematic review and meta-analysis was to demonstrate the clinical outcomes of open surgical repair (OSR) and endovascular aneurysm repair (EVAR) for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of our systematic review and meta-analysis was to demonstrate the clinical outcomes of open surgical repair (OSR) and endovascular aneurysm repair (EVAR) for infective native aortic aneurysms (INAAs).
METHODS
MEDLINE, Embase, and Cochrane Databases were searched for articles reporting OSR and/or EVAR repair of INAA. The methodological quality of included studies was assessed by the Newcastle-Ottawa scale and Moga-Score. Random-effects models were used to calculate the pooled measures.
RESULTS
A total of 34 studies were included, with 22 studies reporting OSR alone, 6 studies reporting EVAR alone and 6 comparative studies for INAAs. The pooled estimates of infection-related complications (IRCs) were 8.2% (95% CI 4.9%-12.2%) in OSR cohort and 23.2% (95% CI 16.1%-31.0%) in EVAR cohort. EVAR was associated with a significantly increased risk of IRCs compared with OSR during follow-up (OR 1.9, 95% CI 1.0-3.7). As for survival outcomes, the summary estimate rate of all cause 30-day, 3-month and 1-year mortality in OSR cohort were 11.7% (95% CI 7.7%-16.1%), 21.6% (95%CI 16.3%-27.4%) and 28.3% (95% CI 20.5%-36.7%; I=50.47%), respectively. For EVAR cohort, the summary estimate rate of all cause 30-day, 3-month and 1-year mortality were 4.9% (95% CI 1.1%-10.4%), 9.4% (95% CI 2.7%-18.7%) and 22.2% (95% CI 12.4%-33.7%), respectively. EVAR was associated with a significantly decreased of 30-day mortality (OR 0.2, 95% CI 0.1-0.6). However, no difference was found between EVAR and OSR in 3-month (OR 0.2, 95% CI 0-1.1), 1-year all-cause mortality (OR 0.4, 95% CI 0.1-1.1) or aneurysm-related mortality (OR 1.4, 95% CI 0.5-3.9). Moreover, no difference of incidence of reintervention was observed (OR 2.6, 95% CI 0.9-7.7; I=53.7%) between two groups.
CONCLUSIONS
EVAR could provide better short-term survival than OSR in patients with INAAs. However, patients undergoing EVAR suffered from higher risks of IRCs. EVAR could be considered as an alternative for low-risk patients with well-controlled infections or patients considered high-risk for open reconstruction.
Topics: Aged; Aneurysm, Infected; Aortic Aneurysm; Blood Vessel Prosthesis Implantation; Endovascular Procedures; Female; Humans; Male; Middle Aged; Postoperative Complications; Retreatment; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 34644648
DOI: 10.1016/j.avsg.2021.07.025 -
Aerospace Medicine and Human Performance Dec 2022There is debate whether astronauts traveling to space should undergo a prophylactic splenectomy prior to long duration spaceflight. Risks to the spleen during flight...
There is debate whether astronauts traveling to space should undergo a prophylactic splenectomy prior to long duration spaceflight. Risks to the spleen during flight include radiation and trauma. However, splenectomy also carries significant risks. Systematic review of data published over the past 5 decades regarding risks associated with splenectomies and risks associated with irradiation to the spleen from long duration spaceflight were analyzed. A total of 41 articles were reviewed. Acute risks of splenectomy include intraoperative mortality rate (from hemorrhage) of 3-5%, mortality rate from postoperative complications of 6%, thromboembolic event rate of 10%, and portal vein thrombosis rate of 5-37%. Delayed risks of splenectomy include overwhelming postsplenectomy infection (OPSI) at 0.5% at 5 yr post splenectomy, mortality rate as high as 60% for pneumococcal infections, and development of malignancy with relative risk of 1.53. The risk of hematologic malignancy increases significantly when individuals reach 40 Gy of exposure, much higher than the 0.6 Gy of radiation experienced from a 12-mo round trip to Mars. Lower doses of radiation increase the risk of hyposplenism more so than hematologic malignancy.For protection against hematologic malignancy, the benefits of prophylactic splenectomy do not outweigh the risks. However, there is a possible risk of hyposplenism from long duration spaceflight. It would be beneficial to prophylactically provide vaccines against encapsulated organisms for long duration spaceflight to mitigate the risk of hyposplenism.
Topics: Humans; Splenectomy; Spleen; Pneumococcal Infections; Postoperative Complications; Space Flight
PubMed: 36757247
DOI: 10.3357/AMHP.6079.2022 -
Europace : European Pacing,... May 2015Infectious complications after cardiac implantable electronic device (CIED) implantation are increasing over time and are associated with substantial mortality and... (Meta-Analysis)
Meta-Analysis Review
Infectious complications after cardiac implantable electronic device (CIED) implantation are increasing over time and are associated with substantial mortality and healthcare costs. The aim of this study was to systematically summarize the literature on risk factors for infection after pacemaker, implantable cardioverter-defibrillator, and cardiac resynchronization therapy device implantation. Electronic searches (up to January 2014) were performed in PubMed, Scopus, and Web of Science databases. Sixty studies (21 prospective, 9 case-control, and 30 retrospective cohort studies) met the inclusion criteria. The average device infection rate was 1-1.3%. In the meta-analysis, significant host-related risk factors for infection included diabetes mellitus (odds ratio (OR) [95% confidence interval] = 2.08 [1.62-2.67]), end-stage renal disease (OR = 8.73 [3.42-22.31]), chronic obstructive pulmonary disease (OR = 2.95 [1.78-4.90]), corticosteroid use (OR = 3.44 [1.62-7.32]), history of the previous device infection (OR = 7.84 [1.94-31.60]), renal insufficiency (OR = 3.02 [1.38-6.64]), malignancy (OR = 2.23 [1.26-3.95]), heart failure (OR = 1.65 [1.14-2.39]), pre-procedural fever (OR = 4.27 [1.13-16.12]), anticoagulant drug use (OR = 1.59 [1.01-2.48]), and skin disorders (OR = 2.46 [1.04-5.80]). Regarding procedure-related factors, post-operative haematoma (OR = 8.46 [4.01-17.86]), reintervention for lead dislodgement (OR = 6.37 [2.93-13.82]), device replacement/revision (OR = 1.98 [1.46-2.70]), lack of antibiotic prophylaxis (OR = 0.32 [0.18-0.55]), temporary pacing (OR = 2.31 [1.36-3.92]), inexperienced operator (OR = 2.85 [1.23-6.58]), and procedure duration (weighted mean difference = 9.89 [0.52-19.25]) were all predictors of CIED infection. Among device-related characteristics, abdominal pocket (OR = 4.01 [2.48-6.49]), epicardial leads (OR = 8.09 [3.46-18.92]), positioning of two or more leads (OR = 2.02 [1.11-3.69]), and dual-chamber systems (OR = 1.45 [1.02-2.05]) predisposed to device infection. This systematic review on risk factors for CIED infection may contribute to developing better infection control strategies for high-risk patients and can also help risk assessment in the management of device revisions.
Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Comorbidity; Defibrillators, Implantable; Electric Countershock; Female; Humans; Male; Middle Aged; Odds Ratio; Prosthesis-Related Infections; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 25926473
DOI: 10.1093/europace/euv053 -
PloS One 2016Periprosthetic joint infection (PJI) is a serious complication of total knee arthroplasty. Two-stage revision is the most widely used technique and considered as the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periprosthetic joint infection (PJI) is a serious complication of total knee arthroplasty. Two-stage revision is the most widely used technique and considered as the most effective for treating periprosthetic knee infection. The one-stage revision strategy is an emerging alternative option, however, its performance in comparison to the two-stage strategy is unclear. We therefore sought to ask if there was a difference in re-infection rates and other clinical outcomes when comparing the one-stage to the two-stage revision strategy.
OBJECTIVE
Our first objective was to compare re-infection (new and recurrent infections) rates for one- and two-stage revision surgery for periprosthetic knee infection. Our second objective was to compare between the two revision strategies, clinical outcomes as measured by postoperative Knee Society Knee score, Knee Society Function score, Hospital for Special Surgery knee score, WOMAC score, and range of motion.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
MEDLINE, EMBASE, Web of Science, Cochrane Library, reference lists of relevant studies to August 2015, and correspondence with investigators.
STUDY SELECTION
Longitudinal (prospective or retrospective cohort) studies conducted in generally unselected patients with periprosthetic knee infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision surgery. No clinical trials comparing both revision strategies were identified.
REVIEW METHODS
Two independent investigators extracted data and discrepancies were resolved by consensus with a third investigator. Re-infection rates from 10 one-stage studies (423 participants) and 108 two-stage studies (5,129 participants) were meta-analysed using random-effect models after arcsine transformation.
RESULTS
The rate (95% confidence intervals) of re-infection was 7.6% (3.4-13.1) in one-stage studies. The corresponding re-infection rate for two-stage revision was 8.8% (7.2-10.6). In subgroup analyses, re-infection rates remained generally similar for several study-level and clinically relevant characteristics. Postoperative clinical outcomes of knee scores and range of motion were similar for both revision strategies.
LIMITATIONS
Potential bias owing to the limited number of one-stage revision studies and inability to explore heterogeneity in greater detail.
CONCLUSIONS
Available evidence from aggregate published data suggest the one-stage revision strategy may be as effective as the two-stage revision strategy in treating infected knee prostheses in generally unselected patients. Further investigation is warranted.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO 2015: CRD42015017327.
Topics: Humans; Knee Prosthesis; Prosthesis-Related Infections; Recurrence; Reoperation
PubMed: 26967645
DOI: 10.1371/journal.pone.0151537 -
The Cochrane Database of Systematic... Jul 2023The optimal treatment for end-stage kidney disease is kidney transplantation. During the operation, a catheter is introduced into the bladder and remains in place... (Review)
Review
BACKGROUND
The optimal treatment for end-stage kidney disease is kidney transplantation. During the operation, a catheter is introduced into the bladder and remains in place postoperatively to allow the bladder to drain. This decreases tension from the cysto-ureteric anastomosis and promotes healing. Unfortunately, urinary catheters can pose an infection risk to patients as they allow bacteria into the bladder, potentially resulting in a urinary tract infection (UTI). The longer the catheter remains in place, the greater the risk of developing a UTI. There is no consensus approach to the time a catheter should remain in place post-transplant. Furthermore, the different timings of catheter removal are thought to be associated with different incidences of UTI and postoperative complications, such as anastomotic breakdown.
OBJECTIVES
This review aimed to compare patients who had their catheter removed < 5 days post-transplant surgery to those patients who had their catheter removed ≥ 5 days following their kidney transplant. Primary outcome measures between the two groups included: the incidence of symptomatic UTIs, the incidence of asymptomatic bacteriuria and the incidence of major urological complications requiring intervention and treatment.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 13 April 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs comparing timing of catheter removal post-transplantation were eligible for inclusion. All donor types were included, and all recipients were included regardless of age, demographics or type of urinary catheter used.
DATA COLLECTION AND ANALYSIS
Results from the literature search were screened by two authors to identify if they met our inclusion criteria. We designated removal of a urinary catheter before five days (120 hours) as an 'early removal' and anything later than this as a 'late removal.' The studies were assessed for quality using the risk of bias tool. The primary outcome of interest was the incidence of asymptomatic bacteriuria. Statistical analyses were performed using the random effects model, and results were expressed as relative risk (RR) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Two studies (197 patients) were included in our analysis. One study comprised a full-text article, and the other was a conference abstract with very limited information. The risk of bias in the included studies was generally either high or unclear. It is uncertain whether early versus late removal of the urinary catheter made any difference to the incidence of asymptomatic bacteriuria (RR 0.89, 95% Cl 0.17 to 4.57; participants = 197; I = 88%; very low certainty evidence). Data on other outcomes, such as the incidence of UTI and the incidence of major urological complications, were lacking. Furthermore, the follow-up of patients across the studies was short, with no patients being followed beyond one month.
AUTHORS' CONCLUSIONS
A high-quality, well-designed RCT is required to compare the effectiveness of early catheter removal versus late catheter removal in patients following a kidney transplant. At the present time, there is insufficient evidence to suggest any difference between early and late catheter removal post-transplant, and the studies investigating this were generally of poor quality.
Topics: Humans; Kidney Transplantation; Urinary Catheters; Bacteriuria; Kidney; Urinary Tract Infections
PubMed: 37449968
DOI: 10.1002/14651858.CD013788.pub2