Continuous and Extended Infusions of β-Lactam Antibiotics in the Pediatric Population

2012 ◽  
Vol 46 (11) ◽  
pp. 1537-1546 ◽  
Author(s):  
Mary Covington Walker ◽  
Weng Man Lam ◽  
Kalen B Manasco
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Continuous Infusion ◽  
Pediatric Patients ◽  
Case Reports ◽  
Pediatric Population ◽  
Case Series ◽  
Current Evidence ◽  
Pharmacokinetic Studies ◽  
Randomized Controlled

OBJECTIVE: To conduct a systematic review of available data on the use of extended or continuous infusion of β-lactam and monobactam therapy in the pediatric population (aged 0–18 years). DATA SOURCES: A literature search was performed using PubMed (1975-May 2012), International Pharmaceutical Abstracts (1970-May 2012), and Web of Science (1977-May 2012) to identify studies for inclusion. In addition, reference citations from identified publications were reviewed. The following search terms were used: pediatric, children, neonate, infant, adolescent, β-lactam, cephalosporin, carbapenem, penicillin, monobactam, continuous infusion, extended infusion, and/or prolonged infusion. Individual names of drugs in each class of antibiotics were also included in the search. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled clinical trials, pharmacokinetic/pharmacodynamic studies, observational studies, and case reports involving pediatric patients who received extended or continuous infusion of β-lactam or monobactam antibiotics were reviewed. Only English-language publications were included. DATA SYNTHESIS: One randomized controlled clinical trial, 5 pharmacokinetic studies, 2 pharmacodynamic studies using Monte Carlo simulation, 1 case series, and 7 case reports were included in the analysis. The cephalosporin class has been studied the most and currently represents the only clinical trial using a continuous infusion dosing strategy in pediatric patients. There is limited clinical evidence available to support the use of extended or continuous infusion of β-lactam antibiotics in the pediatric population. Pharmacodynamic studies conducted in this population mirror the current evidence in adults for cefepime and meropenem. The single prospective clinical trial using continuous infusion of ceftazidime failed to demonstrate any clinical benefit over traditional dosing; however, there was equal efficacy. CONCLUSIONS: More well-designed prospective clinical trials are required to determine the role of extended or continuous infusion of β-lactam antibiotics in treatment of pediatric patients.

scholarly journals Vitamin C in the Treatment of COVID-19

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1172
Author(s):  
Gregorio Paolo Milani ◽  
Marina Macchi ◽  
Anat Guz-Mark
Keyword(s):  
Clinical Trials ◽  
Vitamin C ◽  
Respiratory Infections ◽  
Medical Condition ◽  
Case Reports ◽  
Case Series ◽  
Theoretical Background ◽  
Current Evidence ◽  
Vitamin C Supplementation ◽  
Essential Nutrient

Vitamin C is an essential nutrient that serves as antioxidant and plays a major role as co-factor and modulator of various pathways of the immune system. Its therapeutic effect during infections has been a matter of debate, with conflicting results in studies of respiratory infections and in critically ill patients. This comprehensive review aimed to summarize the current evidence regarding the use of vitamin C in the prevention or treatment of patients with SARS-CoV2 infection, based on available publications between January 2020 and February 2021. Overall, 21 publications were included in this review, consisting of case-reports and case-series, observational studies, and some clinical trials. In many of the publications, data were incomplete, and in most clinical trials the results are still pending. No studies regarding prevention of COVID-19 with vitamin C supplementation were found. Although some clinical observations reported improved medical condition of patients with COVID-19 treated with vitamin C, available data from controlled studies are scarce and inconclusive. Based on the theoretical background presented in this article, and some preliminary encouraging studies, the role of vitamin C in the treatment of patients with SARS-CoV-2 infection should be further investigated.

scholarly journals Opioid Use and the Risk of Respiratory Depression and Death in the Pediatric Population

2013 ◽  
Vol 18 (4) ◽  
pp. 269-276 ◽  
Author(s):  
Marianne R. Whittaker
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Respiratory Depression ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
Opioid Use ◽  
Randomized Controlled ◽  
Randomized Controlled Studies ◽  
Increased Risk ◽  
Significant Difference

BACKGROUND Pediatric patients may be at an increased risk of adverse effects from various medications. Recently, there have been a number of serious adverse events, including several pediatric patients experiencing severe respiratory depression and death as a result of the use of codeine for pain control following tonsillectomy and adenoidectomy. OBJECTIVE To assess the safety of opioid agonists in pediatric patients undergoing operative procedures or have experienced trauma and to evaluate the risk of respiratory depression and death among this population. METHODS PubMed and Medline were searched to identify randomized controlled studies from 1994 to 2012 addressing postsurgery/trauma opioid use in pediatric patients. Relative risks and confidence intervals (CIs) were calculated using data available in clinical trials. RESULTS A total of 16 clinical trials were evaluated for this review. Randomized controlled trials included studies comparing opioids versus non-opioids for a variety of painful conditions. The relative risk of respiratory depression associated with opioid use in 1 trial was 1.63 (95% CI: 0.64–6.13). The remaining 15 trials reviewed described no significant difference in respiratory depression or adverse effects associated with treatment. No deaths were attributed to opioid use in any of these studies. CONCLUSION Opioid-associated respiratory depression was very rare and no deaths were reported in the reviewed studies. These findings under the well-defined conditions of controlled studies may not be the best means of determining overall opioid-associated side effects in pediatric patients.

scholarly journals Arthroscopic Management of Pigmented Villonodular Synovitis of the Hip in Children and Adolescents

2018 ◽  
Vol 6 (3) ◽  
pp. 232596711876311 ◽  
Author(s):  
S. Clifton Willimon ◽  
Tim Schrader ◽  
Crystal A. Perkins
Keyword(s):  
Pediatric Patients ◽  
Case Reports ◽  
Pediatric Population ◽  
Case Series ◽  
Pigmented Villonodular Synovitis ◽  
Villonodular Synovitis ◽  
Arthroscopic Synovectomy ◽  
Duration Of Symptoms ◽  
Pigmented Villonodular

Background: Pigmented villonodular synovitis (PVNS) is a benign proliferative synovial disorder most commonly described to affect the knee in adults. Literature describing PVNS in the pediatric population is limited to 2 small case series and a handful of single-patient case reports. Within these studies, only 2 patients with PVNS of the hip are described. Purpose: To describe the presentation, management, and outcomes of a single-center series of pediatric patients with PVNS of the hip treated with arthroscopic synovectomy. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review of consecutive pediatric patients treated for PVNS at a single institution was performed. Inclusion criteria consisted of patients younger than 19 years with surgically treated PVNS of the hip. Results: Five pediatric patients with a mean age of 11.0 years were treated for PVNS of the hip from 2011 to 2016. The mean duration of symptoms from onset to surgical treatment was 247 days (range, 3-933 days). Upon review of magnetic resonance imaging (MRI) results, radiologists included PVNS in their differential in 3 patients. Seven surgeries were performed in 5 patients. All therapeutic procedures were arthroscopic synovectomies. Nodular PVNS was present in 4 patients, and diffuse disease was present in 1 patient. At a mean 32-month follow-up (range, 12-63 months), all patients were considered to be free of recurrence based on clinical examination and/or follow-up MRI. Four patients were asymptomatic and returned to all of their previous sports activities. Conclusion: Young age at the time of diagnosis is a point to be highlighted in this cohort, and symptoms may be present for many months prior to diagnosis due to the failure to consider PVNS in children. Therefore, for patients with “atypical” presentations or lack of improvement with treatment for rheumatologic, bleeding, or infectious disorders, PVNS should be strongly considered. MRI with gradient echo sequences is the diagnostic imaging study of choice. One patient with diffuse involvement and preoperative degenerative changes showed progressive changes postoperatively. This type of PVNS may have a worse prognosis, but more diffuse cases are needed before the prognosis can be determined. Arthroscopic synovectomy following a timely diagnosis of PVNS produces good outcomes in nodular cases, with no evidence of symptomatic or radiographic disease persistence among these patients.

scholarly journals Role of Plasmapheresis and Extracorporeal Membrane Oxygenation in the Treatment of Leptospirosis Complicated with Pulmonary Hemorrhages

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
C. L. Fonseka ◽  
S. Lekamwasam
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Extracorporeal Membrane Oxygenation ◽  
Study Design ◽  
Case Reports ◽  
Pulmonary Hemorrhage ◽  
Treatment Modalities ◽  
Current Evidence ◽  
Membrane Oxygenation ◽  
Severe Leptospirosis

Introduction. Leptospirosis is an emerging infectious disease associated with multiorgan involvement and significant morbidity and mortality. Although pulmonary hemorrhage due to leptospirosis has a high fatality, specific treatment options are limited and their efficacy is not adequately proven. We opted to find out the current evidence on plasmapheresis and extracorporeal membrane oxygenation (ECMO) in pulmonary hemorrhages due to leptospirosis. Methods. The first search was conducted in PubMed, OVID, Google Scholar, and Cochrane clinical trial registry using keywords “leptospirosis” OR “Leptospira” OR “Weil’s disease” AND “plasmapheresis” OR “plasma exchange” AND “pulmonary hemorrhage” OR “alveolar hemorrhage” OR “lung hemorrhage” and the second search was done using keyword “leptospirosis” OR “Leptospira” OR “Weil’s disease” AND “ECMO” OR “Extracorporeal membrane oxygenation.” The searches were not limited by study design or the date of publication. Only articles written in English were reviewed. Although we intended to include only clinical trials, it was decided later to include other information such as case reports and case series which addressed these treatment modalities. Two authors selected articles independently in a blinded manner using a set of inclusion and exclusion criteria and discrepancies were solved after discussions. Results. The information found was very limited. This included one clinical trial which showed a significant survival benefit with plasmapheresis but the study design had many limitations. Two case reports described the benefit of plasmapheresis in severe leptospirosis with pulmonary hemorrhages. There were eight case reports where ECMO was performed and out of all only one patient has died. One retrospective study on patients with severe leptospirosis mentioned that four out of five patients with pulmonary hemorrhages survived after being treated with ECMO. Conclusions. Current evidence is insufficient to recommend the routine use of plasmapheresis or ECMO for patients presenting with pulmonary hemorrhages due to leptospirosis. ECMO may be a promising mode of treatment in acute respiratory failure in leptospirosis related pulmonary hemorrhages. These treatment modalities, however, can be applied based on the availability of resources and expertise at the discretion of the clinician in charge, considering patient related factors such as cardiovascular stability and derangement of coagulation profile. Clinical trials conducted adhering to standard procedures are urgently required to establish the efficacy of these treatment modalities.

Pharmacokinetics of culture-directed antibiotics for the treatment of peritonitis in automated peritoneal dialysis: A systematic narrative review

2021 ◽  
Vol 41 (3) ◽  
pp. 261-272
Author(s):  
Chau Wei Ling ◽  
Kamal Sud ◽  
Connie Van ◽  
Syed Tabish Razi Zaidi ◽  
Rahul P. Patel ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Case Reports ◽  
Plasma Concentrations ◽  
Case Series ◽  
Therapeutic Drug ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Data ◽  
Automated Peritoneal Dialysis ◽  
Final Study ◽  
Drug Plasma

The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.

Anticoagulation with Warfarin in Infants and Children

1996 ◽  
Vol 30 (11) ◽  
pp. 1316-1322 ◽  
Author(s):  
Marcia L Buck
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Case Reports ◽  
Initial Dosage ◽  
Case Series ◽  
Infants And Children ◽  
Target Range ◽  
Search Term ◽  
Cardiac Valves ◽  
In Infants And Children

OBJECTIVE: TO provide a comprehensive review of warfarin use in infants and children, including recommendations for appropriate dosage and monitoring parameters. DATA SOURCES: A MEDLINE search (1966-1995) was used to identify pertinent English-language articles in the medical literature. The key search term was warfarin. Additional material was obtained from references cited in articles retrieved through MEDLINE. STUDY SELECTION: All articles involving children younger than 18 years were evaluated. In addition, articles on the pharmacokinetics and pharmacodynamics in adults, adverse effects, and drug interactions were included. DATA EXTRACTION: Material selected for review included clinical trials, case reports, and surveys of practice. DATA SYNTHESIS: Warfarin has been used as prophylactic therapy in children with prosthetic cardiac valves as well as for prevention of thromboembolic complications associated with autoimmune disorders and protein C or protein S deficiency. Warfarin also has been used to prevent embolization in children with deep-vein thrombosis or clots in central venous catheters. According to the literature, an initial dosage of 0.1 mg/kg/d should provide anticoagulation without significant adverse effects. As in adults, dosing should be adjusted to achieve a target international normalized ratio (INR). Although the target range in children is not well established, INR values of 1.5–3 are recommended for most patients. Higher values have been used in children with prosthetic cardiac valves and hereditary clotting disorders. CONCLUSIONS: Due to its infrequent use, there is limited information on the effects of warfarin in children. Basic guidelines for initiating and monitoring warfarin were developed by using data gathered from clinical trials, retrospective reviews, case series, and surveys of practice.

Increasing underrepresented minority cancer patient enrollment into cancer clinical trials: A systematic review.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18574-e18574
Author(s):  
Rosa Nouvini ◽  
Patricia A. Parker ◽  
Charlotte Malling ◽  
Kendra Godwin ◽  
Rosario Costas-Muñiz
Keyword(s):  
Systematic Review ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Minority Groups ◽  
Relationship Building ◽  
Institutional Research ◽  
Underrepresented Minority ◽  
Randomized Controlled ◽  
Clinical Trial Enrollment ◽  
Recruitment Model

e18574 Background: Minorities continue to be underrepresented in clinical trials despite the National Institute of Health’s Revitalization Act, passed in 1993, mandating the representation of women and underrepresented minority groups in clinical trials. Studies have shown that although Blacks represent 15% and Hispanics 13% of the cancer population, their clinical trial enrollment rates in are disproportionately low at 4-6% and 3-6% respectively. We conducted a systematic review exploring interventions aimed at improving clinical trial enrollment for racial and ethnic minorities. Methods: A systematic search of PubMed, Cochrane CENTRAL, and Ovid PsycINFO was conducted for English-language studies of humans since 1993. Inclusion criteria included peer-reviewed, U.S.-based studies with interventions aimed to recruit underrepresented minority adult cancer patients into cancer clinical trials. We defined underrepresented minority groups as Black, Hispanic/Latino, Asian, American Indian/Alaska Native and Native Hawaiian/other Pacific Islander. Results: A total of 2471 titles and abstracts were identified and 2324 were excluded based on the eligibility criteria. A full text review was conducted of the remaining 147 articles, of which only 9 met criteria for our review. The interventions included patient navigation/coaching (n = 4), a clinical trial educational video (n = 2), institutional research infrastructure changes (n = 1), a relationship building and social marketing recruitment model (n = 1) and cultural competency training for providers (n = 1). Studies were conducted in a variety of practice settings including national cancer institutes and community practices. The quality of evidence was limited by the heterogeneity of study methods, patient representation and bias. Several studies had a homogeneous population of Black patients. Most studies (n = 7) were single arm trials that compared results to either historical controls or those cited in the existing literature; two studies were randomized controlled trials. A statistically significant improvement in accrual was shown in three of the patient navigation interventions, one of the clinical trial educational videos, the institutional research infrastructure change and the relationship building and social marketing recruitment model. The common threads to many of these successful interventions were support through the cancer care continuum, cultural congruency of research staff and culturally catered clinical trial educational materials. Conclusions: This systematic review illustrates several mechanisms by which to increase cancer clinical trial recruitment for cancer patients of underrepresented minority backgrounds in a variety of clinical settings. Randomized controlled trials with representation of multiple races/ethnicities are needed to further explore the benefits of these interventions.

Immunosuppressive therapy of systemic lupus erythematosus associated peripheral neuropathy: A systematic review

Lupus ◽  
2020 ◽  
Vol 29 (12) ◽  
pp. 1509-1519
Author(s):  
Alexandru Constantin ◽  
Daniela Năstase ◽  
Delia Tulbă ◽  
Paul Bălănescu ◽  
Cristian Băicuș
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Peripheral Neuropathy ◽  
Lupus Erythematosus ◽  
Case Reports ◽  
Immunosuppressive Agents ◽  
Case Series ◽  
Systemic Lupus ◽  
Retrospective Case ◽  
Randomized Controlled ◽  
Neuropsychiatric Manifestations

Introduction Peripheral neurologic manifestations may be associated with most of the collagen vascular diseases including systemic lupus erythematosus (SLE), yet most of the times it is not clear what therapy should be prescribed. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations suggest the use of glucocorticoids and immunosuppressive agents for the treatment of SLE associated peripheral neuropathy (PN) (strength of statement A, category of evidence 1), however these recommendations are based on studies that did not focus specifically on PN but rather on neuropsychiatric manifestations of SLE out of which only one was a randomized controlled clinical trial that included 7 patients with peripheral neuropathy. The objective of this systematic review is to determine whether the pathogenic treatments (corticosteroids, immunosuppressive agents, intravenous immunoglobulins, plasmapheresis) are effective for SLE associated PN. Methods We searched MEDLINE for all the studies that included the pathogenic treatment of SLE associated PN. The purpose was to identify randomized clinical trials, and in the absence of these, we included observational studies and case reports or case series. Results The search returned only retrospective case reports or case series. Only one prospective study, a randomized controlled study, was focused on neuropsychiatric SLE and included few patients with PN (7). Some studies reported cases of PN responsive to glucocorticoids (GC), cyclophosphamide (CYC), rituximab (RTX), azathioprine (AZA), plasmapheresis (PPH), intravenous immunoglobulin (IVIG), mycophenolate mofetil (MMF) or different combinations of these immunosuppressive agents, whereas others noticed effectiveness of sequential treatments (i.e. administration of a therapeutic agent after another single agent or a combination of agents had previously failed). Many studies did not mention how the outcomes were objectively measured. Conclusions There are no interventional studies dedicated to the SLE associated PN, only retrospective case reports or case series which not only did they show contradictory results, but they also represent the lowest level of evidence. There is a strong need for new analytical studies dedicated to SLE associated PN. Protocol registered with PROSPERO (number CRD42019121748).

scholarly journals Robotic adrenalectomy in the pediatric population: initial experience case series from a tertiary center

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anirban P. Mitra ◽  
Evalynn Vasquez ◽  
Paul Kokorowski ◽  
Andy Y. Chang
Keyword(s):  
Hospital Stay ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
Operating Time ◽  
Case Series ◽  
Length Of Hospital Stay ◽  
Open Approach ◽  
Invasive Approach ◽  
Patients Âgés ◽  
Tertiary Center

Abstract Background Laparoscopic resection is the most well described minimally-invasive approach for adrenalectomy. While it allows for improved cosmesis, faster recovery and decreased length of hospital stay compared with the open approach, instrument articulation limitations can hamper surgical dexterity in pediatric patients. Use of robotic assistance can greatly enhance operative field visualization and instrument control, and is in the early stages of adoption in academic centers for pediatric populations. Case presentation We present a single-institution series of pediatric adrenalectomy cases. The da Vinci Xi surgical system was used to perform adrenalectomies on three consecutive patients (ages, 2–13 years) at our center. Final pathology revealed ganglioneuroblastoma (n = 2) and pheochromocytoma (n = 1). Median operating time was 244 min (range, 244–265 min); median blood loss was estimated at 100 ml (range, 15–175 ml). Specimens were delivered intact and all margins were negative. Median post-operative hospital stay was 2 days (range, 1–6 days). All patients remain disease-free at median follow-up of 19 months (range, 12–30 months). Conclusion Our experience continues to evolve, and suggests that robotic surgery is safe, feasible and oncologically effective for resection of adrenal masses in well-selected pediatric patients.

scholarly journals Is Non-Chlamydial Non-Gonococcal Urethritis Associated with Significant Clinical Complications in Men? A Systematic Review

2020 ◽  
Vol 14 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Cassandra E.L. Fairhead ◽  
Alexander Hampson ◽  
Louis Dwyer-Hemmings ◽  
Nikhil Vasdev
Keyword(s):  
Systematic Review ◽  
Reactive Arthritis ◽  
Case Reports ◽  
Case Series ◽  
Current Evidence ◽  
Future Research ◽  
Qualitative Synthesis ◽  
Cross Sectional ◽  
Gonococcal Urethritis ◽  
Clinical Complications

Background: It is estimated that between 50 and 89% of non-gonococcal urethritis is not caused by Chlamydia trachomatis. Associations between non-chlamydial non-gonococcal urethritis (NCNGU) with balanoposthitis, epididymo-orchitis and reactive arthritis have been suggested, but evidence to support these often-theoretical relationships is sparse and further investigation is called for. Concerns over increasing antimicrobial resistance has rendered the need for clarity over this question ever more pressing in recent years. A review of the current evidence on the complications of NCNGU in men is therefore urgently warranted. Objective: This systematic review summarizes and evaluates the available evidence that NCNGU, whether symptomatic or asymptomatic, causes the significant complications that are already well-recognized to be associated with non-gonococcal urethritis. These significant complications are epididymo-orchitis, balanoposthitis, and sexually-acquired reactive arthritis (Reiter's syndrome) including arthritis or conjunctivitis. Summary: We conducted a systematic review and qualitative synthesis using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis framework. Five databases (PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and British Nursing Index) were searched. We included studies that measured clinical outcome after diagnosis of NCNGU in men. Bias was assessed using variations of the Newcastle-Ottawa scale. Data were extracted and entered into a pre-written data abstraction proforma. Seven peer-review studies were included. This included 2 retrospective cohort studies, 1 case series, 2 case reports and 2 cross-sectional studies. The studies described and analyzed 3 types of complication: balanitis, posthitis and/or meatitis; reactive arthritis and/or conjunctivitis; and epididymitis. All studies reported one or more complications. Key Messages: This review identifies an important avenue for future research: while the available evidence suggests that NCNGU has the potential to cause significant complications in men, with the strongest evidence existing for balanitis, posthitis and/or meatitis, the nature and significance of these relationships is far from clear. The findings of this review suggest that prospective, adequately powered research into whether there is a causal link between NCNGU and significant clinical complications in men would be highly worthwhile. The findings of this review raise important questions about the utility of the term NCNGU in research and clinical practice.

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