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Diabetes Care Apr 2022Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.
PURPOSE
To conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes.
DATA SOURCES
We searched PubMed and Embase until 6 March 2021.
STUDY SELECTION
We selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes.
DATA EXTRACTION
Baseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies.
DATA SYNTHESIS
A total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate-corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07-2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69-0.90).
LIMITATIONS
Substantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites.
CONCLUSIONS
Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.
Topics: Amino Acids; Carbohydrates; Diabetes Mellitus, Type 2; Humans; Metabolomics; Observational Studies as Topic; Prospective Studies; Risk Factors
PubMed: 35349649
DOI: 10.2337/dc21-1705 -
American Journal of Obstetrics and... Aug 2020We performed a systematic review and meta-analysis to determine whether D-mannose reduces urinary tract infection recurrence (ie, cumulative incidence) in adult women... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
We performed a systematic review and meta-analysis to determine whether D-mannose reduces urinary tract infection recurrence (ie, cumulative incidence) in adult women with recurrent urinary tract infection compared with other prevention agents. Secondary outcomes included side effects and compliance with D-mannose use.
DATA SOURCES
Ovid Medline 1946-, Embase 1947-, Scopus 1823-, Cochrane Library, Web of Science 1900-, and ClinicalTrials.gov were searched through 4/15/2020.
STUDY ELIGIBILITY CRITERIA
Systematic review inclusion: randomized controlled trials, prospective cohorts, and retrospective cohorts written in English of women ≥18 years old with recurrent urinary tract infection in which D-mannose was utilized as an outpatient prevention regimen. Systematic review exclusion: lab or animal-based research, study protocols only, and conference abstracts. Meta-analysis inclusion: stated D-mannose dose, follow-up time ≥6 months, a comparison arm to D-mannose, and data available from women ≥18 years of age.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two independent reviewers made abstract, full text, and data extraction decisions. Study methodologic quality was assessed using the Cochrane Risk of Bias tool. Relative risks, confidence intervals, and heterogeneity were computed.
RESULTS
Searches identified 776 unique citations. Eight publications met eligibility: 2 using D-mannose only; 6 using D-mannose combined with another treatment. Seven studies were prospective: 2 randomized controlled trials, 1 randomized cross-over trial, and 4 prospective cohort studies. One retrospective cohort study was included. Three studies met meta-analysis eligibility (1 randomized controlled trial, 1 randomized cross-over trial, and 1 prospective cohort). Pooled relative risk of urinary tract infection recurrence comparing D-mannose to placebo was 0.23 (95% confidence interval, 0.14-0.37; heterogeneity=0%; D-mannose n=125, placebo n=123). Pooled relative risk of urinary tract infection recurrence comparing D-mannose to preventative antibiotics was 0.39 (95% confidence interval, 0.12-1.25; heterogeneity=88%; D-mannose n=163, antibiotics n=163). Adverse side effects were reported in 2 studies assessing D-mannose only (1 study (n=10) reported none; the other reported a low incidence (8/103 participants) of diarrhea). Two studies reported compliance, which was high.
CONCLUSION
D-mannose appears protective for recurrent urinary tract infection (vs placebo) with possibly similar effectiveness as antibiotics. Overall, D-mannose appears well tolerated with minimal side effects-only a small percentage experiencing diarrhea. Meta-analysis interpretation must consider the small number of studies with varied study design and quality and the overall small sample size.
Topics: Adult; Anti-Bacterial Agents; Chemoprevention; Diarrhea; Female; Humans; Mannose; Medication Adherence; Recurrence; Urinary Tract Infections
PubMed: 32497610
DOI: 10.1016/j.ajog.2020.05.048 -
The Cochrane Database of Systematic... Aug 2022Urinary tract infections (UTIs) are very common, affecting more than 7 million people worldwide. Whilst many people may only experience a single episode in their... (Review)
Review
BACKGROUND
Urinary tract infections (UTIs) are very common, affecting more than 7 million people worldwide. Whilst many people may only experience a single episode in their lifetime and are generally responsive to standard antibiotics, a significant proportion of adults and children (approximately 15% to 25%) are chronic symptomatic UTI sufferers. Certain population groups are at greater risk than others, such as immunosuppressed and people with chronic kidney disease. D-mannose is a sugar part of normal human metabolism found within most diets. The mechanism of action is to prevent bacterial adherence to the uroepithelial cells. The D-mannose-based inhibitors can block uropathogenic Escherichia coli adhesion and invasion of the uroepithelial cells. The bacteria are then understood to essentially be eliminated by urination. Early pilot studies on animals and humans have trialled concentrated forms of D-mannose (tablets or sachets) in doses ranging from 200 mg up to 2 to 3 g and found possible efficacy in reducing UTI symptoms or recurrence. Although the anti-adhesive effects of D-mannose have been well-established, only recently have we seen a small number of pilot studies and small clinical trials conducted.
OBJECTIVES
To assess the benefits and harms of D-mannose for preventing and treating UTIs in adults and children.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 22 February 2022 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 Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included RCTs measuring and reporting the effect of D-mannose, in any combination and any formulation, to prevent or treat UTIs in adults and children, females and males, in any setting (including perioperative). Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.
DATA COLLECTION AND ANALYSIS
Data extraction was independently carried out by two authors using a standard data extraction form. Methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another author. The certainty of the evidence was assessed using the GRADE approach.
MAIN RESULTS
We included seven RCTs (719 participants) in adult females and males who had either acute cystitis or a history of recurrent (at least two episodes in six months or three episodes in 12 months) UTIs (symptomatic or asymptomatic). Two were prevention studies, four were prevention and treatment studies (two perioperative and one in people with multiple sclerosis), and one was a treatment study. Time periods ranged from 15 days to six months. No two studies were comparable (by dose or treatments), and we could not undertake meta-analyses. Individual studies reported no clear evidence to determine whether D-mannose is more or less effective in preventing or treating UTIs. D-mannose (2 g) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to no treatment (1 study, 205 participants; very low certainty evidence) and antibiotics (nitrofurantoin 50 mg) (1 study, 206 participants; very low certainty evidence). D-mannose, in combination with herbal supplements, had uncertain effects on symptomatic and bacteria-confirmed UTI and pain when compared to no treatment (1 study, 40 participants; very low certainty evidence). D-mannose 500 mg plus supplements (N-acetylcysteine and Morinda citrifolia fruit extract) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to an antibiotic (prulifloxacin 400 mg) (1 study, 75 participants; very low certainty evidence). Adverse events were very few and poorly reported; none were serious (mostly diarrhoea and vaginal burning). Overall, the quality of the evidence is poor. Most studies were judged to have unclear or high risk of bias across most domains. Data was sparse and addressed very few outcomes. The GRADE evaluation was rated as very low certainty evidence due to very serious limitations in the study design or execution (high risk of bias across all studies) and sparse data (single study data and small sample sizes).
AUTHORS' CONCLUSIONS
There is currently little to no evidence to support or refute the use of D-mannose to prevent or treat UTIs in all populations. This review highlights the severe lack of high-quality RCTs testing the efficacy of D-mannose for UTIs in any population. Despite UTIs being one of the most common adult infections (affecting 50% of women at least once in their lifetime) and the growing global antimicrobial resistance, we found very few studies that adequately test this alternative treatment. Future research in this field requires, in the first instance, a single adequately powered RCT comparing D-mannose with placebo.
Topics: Adult; Anti-Bacterial Agents; Bacteriuria; Child; Female; Humans; Kidney; Male; Mannose; Urinary Tract Infections
PubMed: 36041061
DOI: 10.1002/14651858.CD013608.pub2 -
Pathogens (Basel, Switzerland) Dec 2022The use of antibiotics in the treatment of UTIs is contributing to resistance. Hence, the outcome of human clinical trials of nonantibiotic remedies for preventing or... (Review)
Review
The use of antibiotics in the treatment of UTIs is contributing to resistance. Hence, the outcome of human clinical trials of nonantibiotic remedies for preventing or treating UTI is of significant interest. This systematic review aimed to identify, summarise and evaluate the evidence for the outcomes of different nonantibiotic options including cranberry, D-mannose and non-steroidal anti-inflammatory drugs (NSAIDs). PubMed, Embase and Scopus were searched for manuscripts relating to nonantibiotic treatment of UTI including cranberry, mannose and NSAIDs. After title and abstract screening, data were extracted from 21 papers that were published in English and related to the treatment or prevention of uncomplicated UTI in adult women. We identified twelve papers examining the effects of cranberry, two papers examining D-mannose, two papers examining combination treatments (cranberry and D-mannose) and five manuscripts investigating the effects of NSAIDs. There is low-level evidence, from a small number of studies, supporting the use of D-mannose or combination treatments for potentially preventing UTIs in adult women without producing burdening side effects. However, larger and more randomised double-blinded trials are needed to confirm this. In comparison, the multiple studies of cranberry and NSAIDs produced conflicting evidence regarding their effectiveness.
PubMed: 36558804
DOI: 10.3390/pathogens11121471 -
Biomedical Reports Aug 2022Several studies, reviews and meta-analyses have documented that D-mannose use lowers the risk of recurrent urinary tract infections (UTI), but its role in the treatment... (Review)
Review
Several studies, reviews and meta-analyses have documented that D-mannose use lowers the risk of recurrent urinary tract infections (UTI), but its role in the treatment of UTI/cystitis-related symptoms is unclear. In particular, no systematic review has analyzed the role of treatment with D-mannose in acute UTI/cystitis. In this paper, we systematically reviewed the published data on the effect of D-mannose, alone or in association with other compounds, on the typical symptoms of UTI/cystitis. PubMed/Medline and EMBASE databases were searched, from 1990 to January 2022, using combinations of the following keywords: 'urinary tract infections', 'cystalgia', 'recurrent next urinary tract infection', 'cystitis', 'mannose', 'mannoside', 'D-mannose', 'bacteriuria', 'pyuria', 'pyelocystitis' with the appropriate Boolean modifiers (Limits: Human, English, full article). Studies were selected for the systematic review if they were clinical studies and reported original data, the number of patients using D-mannose alone or in association with other treatments, and the number of patients with symptoms of UTI/cystitis at trial entry and after the follow-up period. A total of seven studies were identified. D-mannose was given alone in two studies, and was associated with cranberry extract, fruit extract, pomegranate extract, fructo-oligosaccharides, lactobacilli, and N-acetylcysteine in the others. All studies reported that symptoms decreased after treatment with D-mannose. Despite the limitations of the studies, the consistent results observed among all studies give support to the general findings that D-mannose may be useful in the treatment of UTI/cystitis symptoms.
PubMed: 35815191
DOI: 10.3892/br.2022.1552 -
European Urology Focus Sep 2021The inexorable rise of antimicrobial resistance reinforces the need for alternative approaches to both treat and prevent urinary tract infections (UTIs). A potential... (Review)
Review
The inexorable rise of antimicrobial resistance reinforces the need for alternative approaches to both treat and prevent urinary tract infections (UTIs). A potential approach is administration of D-mannose, an inert monosaccharide that is metabolised and excreted in urine and acts by inhibiting bacterial adhesion to the urothelium. We performed a systematic review to assess the effect of D-mannose in the prevention of recurrent UTIs. Of the eight studies reporting on D-mannose in this context, six were clinical and included 695 individuals. Three studies reported that time to UTI recurrence was longer with D-mannose. D-Mannose improved quality of life and significantly reduced recurrent UTIs in both catheter and non-catheter users. D-Mannose was effective in reducing the incidence of recurrent UTIs and prolonging UTI-free periods, which consequently increased quality of life. PATIENT SUMMARY: D-Mannose is a sugar that seems to reduce the incidence of recurrent urinary tract infections and associated bothersome symptoms. It also leads to a longer duration between episodes of recurrences and consequently improves patient quality of life. D-Mannose can be used as a supplementary or alternate treatment for recurrent urinary tract infections.
Topics: Anti-Bacterial Agents; Humans; Mannose; Quality of Life; Urinary Tract Infections
PubMed: 32972899
DOI: 10.1016/j.euf.2020.09.004 -
Stroke Jan 2021Outcome prognostication in ischemic stroke patients remains challenging due to limited predictive properties of existing models. Blood-based biomarkers might provide...
BACKGROUND AND PURPOSE
Outcome prognostication in ischemic stroke patients remains challenging due to limited predictive properties of existing models. Blood-based biomarkers might provide additional information to established prognostic factors. We intended to identify the most promising prognostic biomarkers in ischemic stroke, their incremental prognostic value, and whether their predictive value differs among etiologies.
METHODS
We searched MEDLINE (Ovid) and Institute for Scientific Information Web of Knowledge for articles reporting the predictive performance of blood-based biomarkers measured up to 7 days after ischemic stroke and reporting functional outcome or death at least 7 days after stroke. This work updates a previous systematic review (up to January 2007), follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and was registered (International Prospective Register of Systematic Reviews PROSPERO 2018; https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42018094671).
RESULTS
Two hundred ninety-one articles published between January 2007 and August 2018 comprising 257 different biomarkers met inclusion criteria. Median sample size was 232 (interquartile range, 110-455); 260 (89%) articles reported regression analyses with 78% adjusting for stroke severity, 82% for age, 67% for both, and 9% for none of them; 37% investigated discrimination, 5% calibration, and 11% reclassification. Including publications from a previous systematic review (1960-January 2007), natriuretic peptides, copeptin, procalcitonin, mannose-binding lectin, adipocyte fatty acid-binding protein, and cortisol were the biomarkers most consistently associated with poor outcome in higher-quality studies showing an incremental value over established prognostic factors. Other biomarkers were less consistently associated with poor outcome or were reported in lower quality studies. High heterogeneity among studies precluded the performance of a meta-analysis.
CONCLUSIONS
The number of reports on prognostic blood-based biomarkers in ischemic stroke increased 3.5-fold in the period January 2007 to August 2018. Although sample size increased, methodological flaws are still common. Natriuretic peptides and markers of inflammation, atherogenesis, and stress response are the most promising prognostic biomarkers among identified studies.
Topics: Animals; Biomarkers; Humans; Ischemic Stroke; Natriuretic Peptides; Prognosis
PubMed: 33430636
DOI: 10.1161/STROKEAHA.120.029232 -
Pharmacological Reviews Apr 2021The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the...
The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the name "complement." Complement is also part of the innate immune system, protecting the host by recognition of pathogen-associated molecular patterns. However, complement is multifunctional far beyond infectious defense. It contributes to organ development, such as sculpting neuron synapses, promoting tissue regeneration and repair, and rapidly engaging and synergizing with a number of processes, including hemostasis leading to thromboinflammation. Complement is a double-edged sword. Although it usually protects the host, it may cause tissue damage when dysregulated or overactivated, such as in the systemic inflammatory reaction seen in trauma and sepsis and severe coronavirus disease 2019 (COVID-19). Damage-associated molecular patterns generated during ischemia-reperfusion injuries (myocardial infarction, stroke, and transplant dysfunction) and in chronic neurologic and rheumatic disease activate complement, thereby increasing damaging inflammation. Despite the long list of diseases with potential for ameliorating complement modulation, only a few rare diseases are approved for clinical treatment targeting complement. Those currently being efficiently treated include paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, and neuromyelitis optica spectrum disorders. Rare diseases, unfortunately, preclude robust clinical trials. The increasing evidence for complement as a pathogenetic driver in many more common diseases suggests an opportunity for future complement therapy, which, however, requires robust clinical trials; one ongoing example is COVID-19 disease. The current review aims to discuss complement in disease pathogenesis and discuss future pharmacological strategies to treat these diseases with complement-targeted therapies. SIGNIFICANCE STATEMENT: The complement system is the host's defense friend by protecting it from invading pathogens, promoting tissue repair, and maintaining homeostasis. Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host's enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.
Topics: COVID-19; Collectins; Complement Activating Enzymes; Complement C3; Complement Inactivating Agents; Complement System Proteins; Genetic Therapy; Humans; Inflammation Mediators; Lectins; Mannose-Binding Protein-Associated Serine Proteases; Pandemics; Rare Diseases; SARS-CoV-2; Synapses; Ficolins
PubMed: 33687995
DOI: 10.1124/pharmrev.120.000072 -
Archives of Gynecology and Obstetrics Oct 2019Urinary tract infections (UTIs) are one of the more common infections encountered in everyday clinical practice. They account for 10-20% of all infections treated in...
PURPOSE
Urinary tract infections (UTIs) are one of the more common infections encountered in everyday clinical practice. They account for 10-20% of all infections treated in primary care units and 30-40% of those treated in hospitals. The risk of UTI in the female population is considered to be 14 times higher than in the male population. The prevalence of bacterial etiology results in a large consumption of broad-spectrum antibiotics, which in turn leads to increased rates of resistant uropathogens. Therefore, non-antibiotic prevention and treatment options are now of great importance.
METHODS
A systematic literature search was performed for the last 20 years (1999-2019) and the efficiencies of these eight different non-antibiotic interventions were analysed and discussed.
RESULTS
This article provides an overview on non-antibiotic options for management of UTI, including the application of cranberry products, the phytodrug Canephron N, probiotics, nonsteroidal anti-inflammatory drugs (NSAID), D-mannose, estrogens, vitamins, and immunotherapy.
CONCLUSIONS
The last 20 years of research on non-antibiotic approaches in UTI have not brought conclusive evidence that antibiotic usage can be replaced completely by non-antibiotic options. Hence, antibiotics still remain a gold standard for UTI treatment and prevention. However, changing the therapeutic strategy by including non-antibiotic measures in the management of UTI could be successful in avoiding antimicrobial resistance at least to some extent.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Female; Humans; Male; Urinary Tract Infections
PubMed: 31350663
DOI: 10.1007/s00404-019-05256-z -
Seminars in Arthritis and Rheumatism Oct 2021We performed a systematic review and meta-analysis for the prevalence and risk factors of rheumatoid arthritis-related bronchiectasis (RA-BR). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We performed a systematic review and meta-analysis for the prevalence and risk factors of rheumatoid arthritis-related bronchiectasis (RA-BR).
METHODS
We queried PubMed and EMBASE databases to identify published literature related to prevalence and risk factors for RA-BR among patients with RA. Data extraction included study design, country, year, method of RA-BR detection, RA characteristics, numerator of RA-BR cases and denominator of patients with RA, and associations with RA-BR presence. We performed a meta-analysis using random or fixed effects models to estimate the prevalence of RA-BR among RA.
RESULTS
Out of a total of 253 studies, we identified 41 total studies that reported on prevalence (n = 34), risk factors (n = 5), or both (n = 2). The included studies had heterogeneous methods to identify RA-BR. Among the 36 studies reporting prevalence, 608 RA-BR cases were identified from a total of 8569 patients with RA. In the meta-analysis, the pooled overall prevalence of RA-BR among RA was 18.7% (95%CI 13.7-24.3%) using random effects and 3.8% (95%CI 3.3-4.2%) using fixed effects. Among studies that used high-resolution chest computed tomography (HRCT) imaging, the prevalence of RA-BR was 22.6% (95%CI 16.8-29.0%) using random effects. When only considering retrospective studies (n = 12), the pooled prevalence of RA-BR among RA was 15.5% (95%CI 7.5-25.5%); among prospective studies (n = 24), the pooled prevalence was 20.7% (95% CI 14.7-27.4%). Risk factors for RA-BR included older age, longer RA duration, genetics (CFTR and HLA), and undetectable circulating mannose binding lectin (MBL) as a biomarker.
CONCLUSION
In this systematic review and meta-analysis, the prevalence of RA-BR was nearly 20% among studies with HRCT imaging, suggesting that bronchiectasis may be a common extra-articular feature of RA. Relatively few factors have been associated with RA-BR. Future studies should standardize methods to identify RA-BR cases and investigate the natural history and clinical course given the relatively high prevalence among RA.
Topics: Aged; Arthritis, Rheumatoid; Bronchiectasis; Humans; Prevalence; Prospective Studies; Retrospective Studies; Risk Factors
PubMed: 34450505
DOI: 10.1016/j.semarthrit.2021.08.005