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Review

Cranberry Excerpt for Symptoms of Astute, Uncomplicated Urinary Tract Infection: A Systematic Review

by * , , , and

Nuffield Department of Main Intendance Health Sciences, University of Oxford, Radcliffe Primary Care Building, Radcliffe Observatory Quarter, Woodstock Route, Oxford OX2 6GG, Britain

*

Author to whom correspondence should be addressed.

Received: 26 November 2020 / Revised: 22 December 2020 / Accepted: 23 Dec 2020 / Published: 25 December 2020

Abstruse

Background: Constructive alternatives to antibiotics for alleviating symptoms of acute infections may be appealing to patients and enhance antimicrobial stewardship. Cranberry-based products are already in wide use for symptoms of acute urinary tract infection (UTI). The aim of this review was to identify and critically assess the supporting evidence. Methods: The protocol was registered on PROSPERO. Searches were conducted of Medline, Embase, Amed, Cinahl, The Cochrane library, Clinicaltrials.gov and WHO International Clinical Trials Registry Platform. We included randomised clinical trials (RCTs) and non-randomised studies evaluating the result of cranberry extract in the management of astute, elementary UTI on symptoms, antibiotic employ, microbiological assessment, biochemical cess and adverse events. Report chance of bias assessments were made using Cochrane criteria. Results: We included 3 RCTs (n = 688) judged to be at moderate adventure of bias. One RCT (n = 309) found that advice to consume cranberry juice had no statistically pregnant event on UTI frequency symptoms (hateful difference (MD) −0.01 (95% CI: −0.37 to 0.34), p = 0.94)), on UTI symptoms of feeling unwell (MD 0.02 (95% CI: −0.36 to 0.39), p = 0.93)) or on antibiotic use (odds ratio 1.27 (95% CI: 0.47 to 3.43), p = 0.64), when compared with promoting drinking water. One RCT (n = 319) establish no symptomatic benefit from combining cranberry juice with immediate antibiotics for an acute UTI, compared with placebo juice combined with immediate antibiotics. In one RCT (northward = 60), consumption of cranberry extract capsules was associated with a within-group improvement in urinary symptoms and Escherichia coli load at day ten compared with baseline (p < 0.01), which was not found in untreated controls (p = 0.72). Two RCTs were under-powered to discover differences between groups for outcomes of interest. At that place were no serious agin effects associated with cranberry consumption. Conclusion: The current prove base for or against the use of cranberry extract in the management of acute, uncomplicated UTIs is inadequate; rigorous trials are needed.

one. Introduction

Women frequently experience symptoms attributed to urinary tract infection (UTI) [ane] and a high proportion receive antibiotic treatment [two]. Increasing antibody resistance has sparked interest in non-antibiotic treatments for common bacterial infections, such as UTIs [iii,4,5,6].

Cranberry fruit (Vaccinium macrocarpon) grows on evergreen shrubs that are native to Due north America [7]. Cranberry fruit is classed every bit a functional food due to the naturally loftier content of compounds, such equally polyphenols, which are believed to take antioxidant and therefore wellness-promoting properties [viii]. The reported health benefits of cranberry consumption range from cardioprotective effects due to improved cholesterol profiles [9] to aiding digestive health [10]. Cranberry exists in diverse forms, including the raw fruit (fresh and dried), cranberry juice and cranberry extract in capsule/tablet formulations [11].

Cranberry excerpt could be a potential culling to antibiotics to treat acute uncomplicated UTIs. Proanthocyanidin (PAC) with A-type linkages, or their metabolites, are believed to be the agile ingredient in cranberry, preventing Escherichia coli (Eastward. coli) from bounden to the bladder uroepithelium [12] and thereby reducing the power of E. coli to cause and sustain a UTI. Systematic reviews assessing the utilize of cranberry in the management of recurrent UTIs provide mixed evidence for do good [13,fourteen]. A 2012 Cochrane review of 24 trials (n = 4473) of men, women and children constitute that cranberry did not significantly reduce recurrent UTI compared with placebo, advice to increase h2o intake or no treatment. A subgroup analysis of women with recurrent UTI found that cranberry consumption resulted in a non-significant reduction in recurrent UTIs [15].

Whilst many studies have evaluated the effectiveness of cranberry extract in reducing recurrent UTI, few have assessed effects on symptoms of acute UTIs [16]. The aim of this systematic review was therefore to synthesise the evidence for the apply of cranberry products in the management of acute, unproblematic UTIs.

2. Methods

2.1. Search Strategy

We conducted searches in Medline, Embase, The Cochrane Library, Amed, Web of Science and Cinahl from inception to tertiary Feb 2020. We also searched ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) and Google Scholar for relevant studies. Search terms included, only were not limited to, cranberry, vaccinium and urinary tract infection (see Table S1 for the comprehensive search strategy). There were no language or time restrictions. We consulted experts in the area and manufacturers of cranberry products (Ocean Spray and Trophikos, LLC) to place relevant studies, and the bibliography of selected articles was hand-searched to find further eligible studies. Manufacturers of cranberry products had no other involvement in this systematic review. Each citation was independently assessed for eligibility by two reviewers (OAG and either JJL or EAS), with disagreements resolved by discussion.

two.2. Eligibility Criteria and Report Option

Nosotros included RCTs (blinded and open-characterization) comparing the effectiveness of cranberry extract with any other treatment for acute uncomplicated UTIs in patients aged 18 years and above. Non-randomised studies (including cohort studies, case–control studies and quasi-randomised studies) assessing the use of cranberry in treating acute UTIs were also eligible. For inclusion, cranberry extract needed to exist orally administered equally juice, fruit or as capsules/tablets/pills. In studies in which a cranberry product was combined with some other intervention/exposure, data allowing the effect of cranberry on the issue(southward) of interest to be isolated were required. Included studies needed to report at least one of our primary or secondary outcomes. Primary outcomes were assessment of participants' symptoms/clinical status/wellbeing assessment (e.yard., symptom burden or time to resolution of symptoms), antibiotic use (immediate and/or delayed) and clinical cure. Secondary outcomes were microbiological cure/cess; biochemical assessment; assessment of mechanisms of activeness; and cess of harms/adverse events.

We excluded studies of exclusively complicated UTI (e.chiliad., catheterised, self-catheterising, spinal string injury, renal tract abnormalities, male UTIs and pyelonephritis); studies assessing recurrent UTI; brute studies; example reports; and systematic reviews. Systematic reviews were used every bit sources for references.

ii.3. Risk of Bias

We assessed the risk of bias of included studies using the Cochrane risk of bias tool [17]. Two reviewers (OAG and EAS) independently assessed the gamble of bias of included studies, with disagreements resolved through give-and-take. The hierarchy of show of included studies was classified according to The Oxford Levels of Evidence 2 criteria [xviii].

2.4. Information Extraction

Nosotros extracted data from included studies on study setting, participants, study elapsing, the intervention and comparator and the results. We reported the hazard of bias across the studies graphically using RevMan [nineteen] and used a summary table to present the results of included studies. The data were independently extracted by 2 reviewers (OAG and EAS), with disagreements resolved through word. We had insufficient data to perform data synthesis and therefore nowadays the results in narrative.

3. Results

3.1. Study Screening

Electronic database searches identified 3337 results (Figure 1). Searching ClinicalTrials.gov, Google Scholar and WHO ICTRP did non place additional studies suitable for inclusion. Later removal of duplicates, 1976 citations were screened at the title and abstract stage and 79 eligible articles were identified. 30 vii studies were excluded because the written report design did not fit our criteria [12,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,fifty,51,52,53,54,55]; a number of these studies assessed the anti-adhesion effects of urine obtained from salubrious volunteers following cranberry consumption, when combined with uropathogen cultures ex vivo. Eleven studies were excluded as they did non assess UTI [56,57,58,59,threescore,61,62,63,64,65,66]. Seven studies were excluded as they assessed recurrent, rather than astute, UTI [67,68,69,70,71,72,73]. Four studies assessed an intervention that did not fit our criteria, such as cranberry extract combined with additional compounds [74,75,76,77]. 2 studies were excluded as updated publications were available for eligibility screening [21,78] and a farther two studies were excluded as they assessed the incorrect patient population [79,80]. I animal study was likewise excluded [81]. Eight studies were excluded as they were duplicates of 5 eligible studies [21,36,43,65,68]. Afterwards initially including seven studies, a farther four were excluded; one was a duplicate [82], the author of a 2d report confirmed that they included patients with complicated UTI [83], one was a trial registration of an ongoing RCT [82] and ane was a completed feasibility RCT with no published results [84]. Iii studies were therefore included in this review [85,86,87].

3.ii. Study Characteristics

All three RCTs were conducted in outpatient settings and included betwixt 60 [87] and 319 [85] participants (Table 1). One written report each was conducted in the Us [85], India [87] and the United kingdom [86]. The intervention used in two of the RCTs was cranberry juice [85,86], whilst the other trial used encapsulated cranberry powder [87]. The PAC content of the interventions varied greatly; participants in one study received between 7.5 (low dose) and 15 mg (high dose) of PAC daily [87], whilst participants in another study received on average 224 mg of PAC daily [85]. Ane study did not report the PAC content in the intervention [86].

The included RCTs provided information on outcomes relevant to this review; still, the primary objective of the studies was not assessment of cranberry extract for acute UTI. 2 studies focused on cranberry for preventing recurrent UTI [85,87]. Barbosa-Cesnik et al. recruited women with an acute UTI, treating the index UTI with immediate antibiotics and meantime randomly assigning the participants to receive either 8 ounces of 27% low-calorie cranberry juice twice daily or 8 ounces of placebo juice twice daily for six months [85]. Women were followed upward for 6 months or until they experienced a UTI, whichever came sooner. Sengupta and colleagues randomly assigned sixty women to receive either low-dose encapsulated cranberry powder (500 mg daily), high-dose encapsulated cranberry powder (k mg daily) or no treatment [87]. The principal outcome was the ability of the unlike handling regimens to prevent recurrent UTI over a 90-solar day period.

The primary objective of the trial by Niggling et al. was to determine the effectiveness of five treatment strategies in the management of suspected acute, simple UTI, with participants randomly assigned to: (ane) immediate antibiotics; (ii) delayed antibiotics; (3) antibiotics dependent on the participant's symptom score; (iv) antibiotics offered if the dipstick was positive; and (five) antibiotics targeted to according to midstream urine results [88]. Four forms of cocky-help advice were randomised beyond the five groups in a factorial design and included: (1) information leaflet with tips on self-assist; (2) communication to utilise over-the-counter herbal remedies; (3) advice to employ bicarbonate; and (4) communication to drink at least 3–4 litres per day and to make at least 1 litre of this cranberry juice or orange juice.

iii.iii. Risk of Bias

The risk of bias of included studies was judged equally moderate (Figure 2a,b), providing level ii (randomised clinical trial) evidence co-ordinate to The Oxford Levels of Testify 2 criteria [18]. All three studies were judged to have a depression chance of option bias and reporting bias. The RCT by Sengupta et al. is described by the written report authors as double-blind; however, women in the control group did not receive a placebo [87]. Information technology was therefore judged past the review authors to take a high risk of bias with respect to participant blinding. The open-label RCT by Little et al. was similarly judged to take a high risk of bias for this domain [86]. Two of the three RCTs were judged to accept a high take a chance of bias with respect to incomplete outcome data; Sengupta et al. [87] did not conduct intention to care for (ITT) analyses, whilst Barbosa-Cesnik et al. [85] conducted ITT analysis only had high attrition (26%).

Additional biases included cranberry industry involvement [85] and insufficient power to detect betwixt-group differences for cranberry comparisons [86,87]. According to the power calculation by Barbosa-Cesnik and colleagues [85], recruiting 120 participants in both arms would have provided the study with 80% power to detect between-group differences, bold that 30% of participants experienced a UTI during the follow-upwardly menstruum. In social club to accept into account greater loss to follow-upward that might occur in the cranberry group compared with the placebo group, the authors planned to recruit 200 participants per group (400 in total). Although 419 women were randomised, 100 women had negative urine cultures and were therefore non eligible for the study and did not receive cranberry or placebo juice. Therefore, 319 women were included in the ITT analysis—less than the authors had planned. Loss to follow-up was not higher in the cranberry group compared with the placebo group; however, recurrence of UTI occurred in 16.9% of participants—lower than anticipated by the authors—which may have adversely impacted the power of the written report.

3.4. Symptoms

Little et al. [86] analysed the impact of the unlike treatment strategies on "frequency symptoms" (day-time and night-time urinary frequency, dysuria and urgency) and "unwell symptoms" (restriction of usual activities, abdominal pain and feeling unwell). There was no significant event of advice to drinkable cranberry juice on the severity of frequency symptoms (hateful divergence (Dr.) −0.01 (95% CI: −0.37 to 0.34), p = 0.94)) or the severity of unwell symptoms (Doc 0.02 (95% CI: −0.36 to 0.39), p = 0.93)), compared with advice to drink water. Advice to potable cranberry juice compared with water did non touch the duration of symptoms rated moderately bad or worse—that is, rated three or more on a scale of zero to six (incident rate ratio (IRR) 1.18 (95% CI: ane.95 to 1.47), p = 0.13)).

Sengupta and colleagues reported a significant within-group improvement in symptoms at x days compared with baseline in both the high- and low-dose cranberry intervention groups, but not in the untreated controls [87]. No empirical data were presented to support this finding, nor were betwixt group comparisons reported.

Barbosa-Cesnik et al. [85] reported that at 3 days and at 1–2 weeks later enrolment in the trial, the presence of urinary symptoms and vaginal symptoms was similar between the cranberry and placebo juice groups. No empirical data were presented to support this finding. In this study, all women received immediate antibiotics to treat their index UTI; thus, the findings described represent the effect of cranberry juice in addition to immediate antibiotics.

3.5. Antibiotic Utilize

Petty et al. [86] constitute that advice to consume cranberry juice had no significant impact on the apply of antibiotics, compared with advice to drink h2o (odds ratio (OR) 1.27 (95% CI: 0.47 to 3.43), p = 0.64).

3.half-dozen. Microbiological Assessment

Sengupta et al. [87] reported a significant within-group reduction in E. coli load after ten days of handling with both depression-dose cranberry (p < 0.01) and high-dose cranberry (p < 0.0001), only not in the untreated controls (p = 0.72). At baseline, 4/xiii (30.8%) of the untreated controls were East. coli positive, whilst 14/21 (66.7%) of the low-dose cranberry group and 17/23 (73.ix%) of the loftier-dose cranberry group were E. coli positive.

3.7. Time to Reconsultation

There was no significant bear upon of cranberry juice consumption on fourth dimension to re-consultation compared with advice to drink h2o (adventure ratio (60 minutes) 0.74 (95% CI: 0.49 to 1.13), p = 0.17)) in the RCT by Lilliputian and colleagues [86].

3.8. Serious Adverse Events

There were no major adverse events (defined as major illness, admission to hospital, death) reported for any group in the trial by Fiddling et al. [86]. Sengupta et al. [87] similarly reported that no serious adverse events occurred during the course of the study. Barbosa-Cesnik and colleagues institute that serious adverse events occurred equally between groups, and none were deemed to be related to treatment received in the trial [85].

4. Word

The current evidence base for or against the use of cranberry excerpt in the management of acute, simple UTIs is inadequate. The existing, limited RCT evidence identified suggests that advice to consume cranberry juice does not ameliorate urinary frequency symptoms, feeling unwell or the elapsing of symptoms rated moderately bad or worse in women with astute UTIs, compared with encouraging the consumption of water. Advice to consume cranberry juice did not reduce the employ of antibiotics compared with promoting the consumption of water or time to re-consultation. In women receiving immediate antibiotics and cranberry juice, urinary symptoms were non reduced compared with firsthand antibiotics and placebo juice. Consuming encapsulated cranberry pulverization may reduce E. coli load and improve symptoms after ten days of consumption compared with baseline. The studies did not written report evidence of serious damage associated with cranberry consumption. These results must exist interpreted with caution as they come from a express number of studies with a moderate risk of bias for the outcomes of interest in this review, which were not the principal objectives of the trials.

four.i. Comparison with Existing Literature

We identified two trial registrations pertinent to this review. One of these trials, an open-label RCT in Spain, aims to recruit 128 women from emergency departments and outpatient clinics with acute UTI to assess the non-inferiority of astute treatment with a Cysticlean cranberry capsule (containing 240 mg PAC) compared with a iii-gram stat dose of Fosfomycin [82]. The primary event measures include a comparison of women experiencing "treatment failure" and patient-reported symptoms. The 2d study is an open-label feasibility RCT in the U.k., in which 46 women recruited from GP practices with symptoms suggestive of an acute UTI were randomly assigned to receive: (1) immediate antibiotics; (2) immediate antibiotics and cranberry capsules for upwardly to seven days (72 mg PAC per mean solar day); or (3) immediate cranberry capsules for up to 7 days (72 mg PAC per day), with a prescription of redundancy antibiotics in case symptoms did not improve with cranberry alone, or worsened [84]. The master outcomes of this feasibility trial relate principally to the ability to recruit participants, the ability to capture data through participant completed symptom diaries and the acceptability of the written report procedures and intervention to participants. Dissemination of the findings of these two studies should provide a useful improver to the electric current, express bear witness base and may serve as a platform for further enquiry assessing cranberry extract as a treatment for symptoms of astute UTI.

A Cochrane review assessing cranberry products for symptoms of astute UTIs, last updated in 2020, did not notice any eligible studies, nor did information technology identify either of the trial registrations discussed higher up [36]. This review therefore provides additional pertinent information.

Howell et al. [65] conducted a randomised double-blind study to determine the optimal amount of PAC to consume to provide E. coli anti-adhesion activeness in urine. Urine samples were collected from study participants earlier and afterwards consuming cranberry capsules containing varying amounts of PAC or placebo capsules. The anti-adhesion activity of the participants' urine was tested ex vivo against a uropathogenic Eastward. coli strain. There was a meaning increase in the anti-adhesion activity of PAC compared with placebo (p < 0.001), and the outcome increased in a dose-dependent mode. They determined that the optimal corporeality of PAC to consume was 72 mg per day. In the report by Piffling et al., the amount of PAC consumed past participants in the cranberry juice arm was non specified, and in the trial by Sengupta et al., participants in the high-dose cranberry group received 15 mg of PAC daily. Information technology is therefore possible that participants in the cranberry arms of these studies were consuming sub-therapeutic doses of what is believed to be the active ingredient in the intervention.

Some studies have found that advice to take not-steroidal anti-inflammatories (NSAIDS) reduces the consumption of antibiotics for astute urinary tract infections, although they control UTI symptoms less effectively than antibiotics and patients had more than cases of pyelonephritis [three,4,vi,89]. Should cranberry prove to be an constructive handling for acute urinary tract infection, cranberry may confer sure advantages over NSAIDS, such as the appeal of consuming a natural production, as well every bit additional purported health benefits of cranberry within the urinary tract and elsewhere [eighty]. Potential harm associated with cranberry consumption, notwithstanding, must be considered. In that location is mixed evidence of an interaction between cranberry and Warfarin [ninety] and of an association with urolithiasis [91].

four.2. Strengths and Limitations

We employed a broad search strategy to maximise the chance of capturing relevant studies, including grayness literature. In addition to electronic database searches and trial registries, we contacted companies that sell cranberry products and experts in the field. When needed, we contacted authors of eligible studies to check whether they were suitable for inclusion.

However, nosotros recognise that there are limitations to this review. We identified few studies suitable for inclusion, with moderate risk of bias, and empirical data were non provided for all of the outcomes assessed in this review. This is probably in part considering cranberry extract as an acute UTI treatment was not the chief focus of the included RCTs. It is possible that we may take missed some studies that were suitable for inclusion, particularly unpublished studies. There was heterogeneity in the outcomes reported by the studies, and in the corporeality of PAC in the interventions used, making it difficult to make straight comparisons betwixt studies.

Two of the studies were nether-powered to determine the furnishings of cranberry on outcomes, which can atomic number 82 to exaggerated effect sizes [92]. One report had loftier attrition, and another did not comport intention to treat analyses.

I study reported within-group comparisons rather than betwixt-group comparison; this can lead to high Blazon I error (rejection of a true cipher hypothesis) and misleading results [93]. Whilst Little et al. [86] did not notice that cranberry improved UTI symptoms or antibody usage, the study authors noted that well-nigh half of the participants who were advised to drink water solitary reported drinking cranberry juice (49%). It is possible that "contagion" of the comparator grouping may have introduced Blazon Ii fault (non-rejection of a simulated nada hypothesis), making cranberry juice appear less constructive than information technology is.

four.3. Implications for Time to come Research and Clinical Practice

Few studies have assessed the utility of cranberry in treating symptoms of acute UTIs; further adequately powered, well-conducted randomised clinical trials are required. These studies should apply standardised interventions with a specified amount of PAC and must likewise report potential harm associated with cranberry consumption. It would also be helpful if the outcomes reported were standardised, to allow directly comparisons to exist made betwixt studies and meaningful meta-analysis of multiple studies to be performed. Given that cranberry extract is normally used by women for symptoms of acute UTI, disseminating the results of well-conducted studies evaluating cranberry extract as a treatment for astute UTI to both clinicians and the public will be of import.

There is a drive towards increasing the utilize of delayed antibody prescription for self-limiting bacterial infections in primary care [94]. In primary intendance, this strategy has been shown to reduce antibiotic prescription for acute respiratory infections by 40% [95] and for UTI by 20% [96]. If cranberry were plant to be constructive in robust clinical trials in managing acute uncomplicated UTIs, it could be incorporated into a delayed antibiotic prescribing strategy; women could be advised to take cranberry products initially, taking antibiotics only if symptoms fail to amend or worsen. However, in light of the very limited prove, no clinical recommendations can be fabricated at present.

5. Conclusions

There is a paucity of studies evaluating cranberry in the management of acute UTIs; none of the identified trials were primarily focused on cranberry as an astute UTI treatment. The existing studies are at moderate risk of bias. Evidence of the effectiveness and prophylactic of cranberry extract as a treatment for symptoms of acute, unproblematic UTI is inconclusive; rigorous trials addressing these outcomes are required.

Supplementary Materials

Author Contributions

O.A.1000.—Protocol development, screening of abstracts, data extraction and assay, run a risk of bias assessment, and writing of the review. E.A.S.—Screening of abstracts, data extraction, risk of bias cess, and co-drafting of the re-view. J.J.L.—Protocol development, screening of abstracts and co-drafting of the review. C.J.H.—Protocol development and co-drafting of the review. C.C.B.—Protocol development and co-drafting of the review. E.A.S.—Screening of abstracts, information extraction, hazard of bias assessment, and co-drafting of the review. All authors take read and agreed to the published version of the manuscript.

Funding

O.A.G. is funded by the Wellcome Trust (grant number 203921/Z/16/Z) and the National Institute of Health Research School for Primary Intendance Research (grant number BZR00880 BZ01.49). E.A.S. is funded past the NIHR grant Improving the evidence-base for chief intendance: NIHR Evidence Synthesis working group extension, grant number 461. C.J.H. received funding support from the NIHR SPCR Testify Synthesis Working Group (projection 390) and the NIHR Oxford BRC. J.J.L. is funded by a NIHR clinical doctoral fellowship. The views are those of the authors and not necessarily those of the Wellcome Trust, the NIHR or Section of Health and Social Care.

Acknowledgments

We would like to thank Nia Roberts for helpful discussions regarding the search strategy.

Conflicts of Interest

O.A.K. received grant funding from the Wellcome Trust and the National Institute of Health Research Schoolhouse for Primary Care Enquiry. E.A.Southward. and J.J.Fifty. have no disharmonize of interest to declare. C.J.H. reports he has received expenses and fees for his media work. He is Managing director of the CEBM at the University of Oxford, and Editor in Chief of BMJ Bear witness-Based Medicine and an NIHR Senior Investigator. C.C.B. is; a Senior Investigator of the National Institute of Health Research; Clinical Manager of the University of Oxford Main Care and Vaccines Collaborative Clinical Trials Unit of measurement; Clinical Manager of the NIHR Oxford Community Medtech and Invitro diagnostics Cooperative, and; salaried full general practitioner for the Cwm Taf Morgannwg University Health Board. He has received funding from many public funding bodies for chief care research related to the management of common infections. He received payment for contributing to Advisory Boards for Pfizer in 2019, Roche Diagnostics in 2020, and for contributing to an Advisory Board for Janssen Pharmaceuticals about Respiratory Syncytial Virus treatment and vaccination from Janssen Pharmaceuticals in 2020, and holds an unrestricted grant form Janssen Pharmaceuticals for contributing to research on Respiratory Syncytial Virus.

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Figure 1. Menstruum chart showing the process for identification of studies eligible for inclusion.

Effigy one. Menstruation nautical chart showing the process for identification of studies eligible for inclusion.

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Effigy 2. (a) Risk of bias graph: review authors' judgements about each take a chance of bias particular presented as percentages across all included studies. (b) Risk of bias summary: review authors' judgements nearly each adventure of bias item for each included report.

Figure 2. (a) Take chances of bias graph: review authors' judgements well-nigh each take a chance of bias detail presented equally percentages across all included studies. (b) Take chances of bias summary: review authors' judgements about each risk of bias item for each included study.

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Table 1. Characteristics of included studies and cardinal results.

Table one. Characteristics of included studies and central results.

Study ID and State Blueprint Participants and Setting Number of Participants Age (years) Study Duration Intervention Control Results
Barbosa-Cesnik et al. (2011), USA [85] Randomised placebo-controlled trial Women with an astute UTI (three or more than urinary symptoms) presenting for urinalysis at the University of Michigan Health Service laboratory with symptoms of UTI 319 (155 received cranberry, 164 received placebo) 18–40 6 months 8 ounces of 27% low-calorie cranberry juice twice daily 8 ounces of placebo juice twice daily The presence of urinary and vaginal symptoms was similar between groups at iii days and at one–two weeks.
Little et al. (2009), UK [86] Randomised controlled trial Not-significant women presenting to General Practices in Due south-Westward England with a suspected elementary UTI 309 (241 women in the juice comparisons: 75 advised to take cranberry juice, 78 advised to take orange juice, 88 advised to drinkable water) 17–70 Average follow-upward time of 575 days (range 35–968 days) Advice to drink cranberry juice Advice to beverage water No significant touch on of communication to consume cranberry juice on the duration of symptoms rated moderately bad or worse (IRR 1.18 (95% CI: ane.95 to 1.47), p = 0.13), frequency symptom severity (hateful difference −0.01 (95% CI: −0.37 to 0.34), p = 0.94), severity of unwell symptoms (mean difference 0.02 (95% CI: −0.36 to 0.39), p = 0.93), employ of antibiotics (odds ratio ane.27 (95% CI: 0.47 to 3.43) p = 0.64) or time to re-consultation (hazard ratio 0.74 (95% CI: 0.49 to 1.thirteen), p = 0.17).
Sengupta et al. (2011), India [87] Randomised controlled trial Women with balmy symptoms of a UTI, urine culture positive and with a negative pregnancy test threescore (xvi untreated controls, 21 received low dose cranberry, 23 received high dose cranberry) 18–forty xc days Encapsulated PAC Standardised Whole Cranberry Pulverisation (PS-WCP)—500 (depression dose) and 1000 mg (high dose) No treatment Significant within-grouping improvement of symptoms at day ten compared to the baseline in both treatment groups, but not in the untreated controls. Pregnant within-group reduction in E. coli load in both treatment groups subsequently 10 days of treatment (depression dose, p < 0.01; high dose p < 0.0001; at a statistical significance level of 95%), simply not in the untreated controls (p = 0.72).

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