Effect of Probiotic Supplementation on Cariogenic Streptococcus mutans Levels: A Systematic Review and Network Meta-Analysis.

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To systematically evaluate and quantitatively compare, through pairwise and network meta-analysis, the effectiveness of probiotic supplementation in reducing cariogenic Streptococcus mutans levels in human subjects. A comprehensive search was conducted in PubMed, Scopus, Embase, Web of Science and Cochrane Library up to October 2025. Randomised controlled trials assessing probiotic or synbiotic formulations with quantitative S. mutans outcomes were included. Data expressed as mean ± standard deviation were synthesised under a random-effects model using a frequentist network meta-analysis (netmeta, R). Effect sizes were reported as mean differences (MD, 95% CI). To strengthen analytical validity, all outputs were cross-validated through triangulation using the MetaInsight platform, confirming consistency between independent computational environments. Risk of bias was assessed with RoB 2, and evidence certainty was appraised via CINeMA. Twenty trials fulfilled inclusion criteria. Most interventions showed a short-term reduction in S. mutans counts, but differences versus placebo were small and not statistically significant across intervals. Forest-plot synthesis and triangulated results indicated that effects were transient and strain-dependent. SUCRA rankings suggested a high percentage of success, but those findings are only probabilistic, not conclusive superiority. Overall evidence certainty was low to moderate. Probiotic supplementation exhibited a limited, time-dependent capacity to modulate S. mutans levels without a consistent advantage over placebo. Current findings support its role as a safe adjunctive rather than as a standalone preventive strategy. Within the available evidence, probiotics should be regarded as experimental adjuncts rather than as replacements for conventional caries-prevention measures. Any observed microbiological benefits were modest, transient and strain-specific, without consistent translation into clinical outcomes. Their recommendation should remain cautious until larger, long-term randomised trials confirm durable effects. PROSPERO registration number: CRD420251180536.

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  • PloS one
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Comparative effectiveness of electroacupuncture and conventional acupuncture for rheumatoid arthritis pain: A network meta-analysis with emphasis on placebo control validity.
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  • Journal of integrative medicine
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  • 10.1002/14651858.cd013325.pub2
Interventions for treating people with symptoms of bladder pain syndrome: a network meta-analysis.
  • Jul 30, 2020
  • The Cochrane database of systematic reviews
  • Mari Imamura + 6 more

Bladder pain syndrome (BPS), which includes the condition of interstitial cystitis, is a poorly understood clinical condition for which patients present with varying symptoms. Management of BPS is challenging for both patients and practitioners. At present, there is no universally accepted diagnosis and diverse causes have been proposed. This is reflected in wide-ranging treatment options, used alone or in combination, with limited evidence. A network meta-analysis (NMA) simultaneously comparing multiple treatments may help to determine the best treatment options for patients with BPS. To conduct a network meta-analysis to assess the effects of interventions for treating people with symptoms of bladder pain syndrome (BPS). We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL, in the Cochrane Library), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and handsearched journals and conference proceedings (searched 11 May 2018) and the reference lists of relevant articles. We conducted a further search on 5 June 2019, which yielded four small studies that were screened for eligibility but were not incorporated into the review. We included randomised controlled trials (RCTs) and quasi-RCTs of interventions for treating adults with BPS. All types of interventions (including conservative, pharmacological and surgical) were eligible. We assessed the risk of bias of included studies using Cochrane's 'Risk of bias' tool. Primary outcomes were the number of people cured or improved, pain, frequency and nocturia. For each outcome, random-effects NMA models were fitted using WinBUGS 1.4. We monitored median odds ratios (ORs) for binary outcomes and mean differences (MDs) for continuous outcomes with 95% credible intervals (Crls). We compared results of the NMA with direct evidence from pairwise meta-analysis of head-to-head trials. We used the CINeMA tool to assess the certainty of evidence for selected treatment categories. We included 81 RCTs involving 4674 people with a median of 38 participants (range 10 to 369) per RCT. Most trials compared treatment against control; few trials compared two active treatments. There were 65 different active treatments, and some comparisons were informed by direct evidence from only one trial. To simplify, treatments were grouped into 31 treatment categories by mode of action. Most studies were judged to have unclear or high risk of bias for most domains, particularly for selection and detection bias. Overall, the NMA suggested that six (proportion cured/improved), one (pain), one (frequency) and zero (nocturia) treatment categories were effective compared with control, but there was great uncertainty around estimates of effect. Due to the large number of intervention comparisons in this review, we focus on three interventions: antidepressants, pentosan polysulfate (PPS) and neuromuscular blockade. We selected these interventions on the basis that they are given 'strong recommendations' in the EAU Guidelines for management of BPS (EAU Guidelines 2019). We found very low-certainty evidence suggesting that antidepressants were associated with greater likelihood of cure or improvement compared with control (OR 5.91, 95% CrI 1.12 to 37.56), but it was uncertain whether they reduced pain (MD -1.27, 95% CrI -3.25 to 0.71; low-certainty evidence), daytime frequency (MD -2.41, 95% CrI -6.85 to 2.05; very low-certainty evidence) or nocturia (MD 0.01, 95% CrI -2.53 to 2.50; very low-certainty evidence). There was no evidence that PPS had improved cure/improvement rates (OR 0.14, 95% CrI 0.40 to 3.35; very low-certainty evidence) or reduced pain (MD 0.42, 95% CrI -1.04 to 1.91; low-certainty evidence), frequency (MD -0.37, 95% CrI -5.00 to 3.44; very low-certainty evidence) or nocturia (MD -1.20, 95% CrI -3.62 to 1.28; very low-certainty evidence). There was evidence that neuromuscular blockade resulted in greater cure or improvement (OR 5.80, 95% CrI 2.08 to 18.30) but no evidence that it improved pain (MD -0.33, 95% CrI -1.71 to 1.03), frequency (MD -0.91, 95% CrI -3.24, 1.29) or nocturia (MD -0.04, 95% CrI -1.35 to 1.27). The certainty of this evidence was always very low. We are uncertain whether some treatments may be effective in treating patients with BPS because the certainty of evidence was generally low or very low. Data were available for a relatively large number of trials, but most had small sample sizes and effects of treatments often could not be estimated with precision. An NMA was successfully conducted, but limited numbers of small trials for each treatment category hampered our ability to fully exploit the advantages of this analysis. Larger, more focused trials are needed to improve the current evidence base.

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  • Cite Count Icon 1
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Effectiveness of Articular and Neural Mobilization for Managing Cervical Radicular Pain: A Systematic Review With Network Meta-Analysis.
  • May 16, 2025
  • The Journal of orthopaedic and sports physical therapy
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OBJECTIVE: To evaluate the impact of articular and neural mobilization on pain intensity and disability in patients with cervical radicular pain. DESIGN: Intervention systematic review with network meta-analysis. LITERATURE RESEARCH: The MEDLINE, SciELO, PubMed, PEDro, Scopus, Web of Science, and Cochrane databases were searched up to February 2024. STUDY SELECTION CRITERIA: Randomized controlled trials studying the effects of articular or neural mobilization in adults with cervical radicular pain were included. DATA SYNTHESIS: A frequentist network meta-analysis was used to assess pain intensity and disability. The risk of bias and the certainty of the evidence were evaluated using Version 2 of the Cochrane Risk of Bias (RoB 2) tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, respectively. RESULTS: Out of 777 reports, 50 were analyzed quantitatively. The combination of articular and neural mobilization with usual care was most effective in reducing short-term pain intensity compared to wait and see, sham, or placebo interventions (mean difference [MD], -3.23; 95% confidence interval [CI]: -4.33, -2.12) and to standard care alone (MD, -1.52; 95% CI: -2.31, -0.73). There were significant improvements in pain-related disability with neural mobilization plus usual care, surpassing wait and see, sham, placebo interventions (standardized mean difference [SMD], -1.57; 95% CI: -2.53, -0.61), and usual care alone (SMD, -1.31; 95% CI: -1.88, -0.73). Risk of bias and heterogeneity of included trials downgraded the certainty of evidence. CONCLUSION: Combining mobilization techniques with standard care may be considered in clinical practice, although with care due to the moderate to very low certainty of the evidence. J Orthop Sports Phys Ther 2025;55(7):1-14. Epub 16 May 2025. doi:10.2519/jospt.2025.12757.

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  • Cite Count Icon 7
  • 10.1186/s12889-024-19348-2
Effects of exercise on depression and anxiety in postmenopausal women: a pairwise and network meta-analysis of randomized controlled trials
  • Jul 8, 2024
  • BMC Public Health
  • Bing Han + 6 more

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  • Research Article
  • Cite Count Icon 19
  • 10.1038/s41430-023-01270-2
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  • Feb 14, 2023
  • European Journal of Clinical Nutrition
  • Harshad Panchal + 3 more

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Comparative efficacy of different mind-body exercise modalities in low back pain: Systematic review and network meta‑analysis.
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  • Complementary therapies in medicine
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Relative efficacy of prehabilitation interventions and their components: systematic review with network and component network meta-analyses of randomised controlled trials
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ObjectiveTo estimate the relative efficacy of individual and combinations of prehabilitation components (exercise, nutrition, cognitive, and psychosocial) on critical outcomes of postoperative complications, length of stay, health related quality of...

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Lack of Efficacy of Bone Void Filling Materials in Medial Opening-Wedge High Tibial Osteotomy: A Systematic Review and Network Meta-analysis
  • Dec 26, 2022
  • Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
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Clinical Outcomes of Different Warfarin Self-Care Strategies: A Systematic Review and Network Meta-Analysis.
  • Jan 20, 2022
  • Thrombosis and haemostasis
  • Teerapon Dhippayom + 5 more

To compare the effects of different strategies for warfarin self-care. PubMed, EMBASE, CENTRAL, CINAHL, ProQuest Dissertations & Theses, and OpenGrey were searched from inception to August 2021. Randomized controlled trials (RCTs) of warfarin self-care, either patient self-testing (PST) or patient self-management (PSM), were included. Self-care approaches were classified based on the TIP framework (theme, intensity, provider): (1) PST ≥1/week via e-Health (PST/High/e-Health); (2) PST ≥1/week by health care practitioner (PST/High/HCP); (3) PST <1/week via e-Health (PST/Low/e-Health); (4) PSM ≥1/week by e-Health (PSM/High/e-Health); (5) PSM ≥1/week by patient (PSM/High/Pt); (6) PSM <1/week by patient (PSM/Low/Pt); and (7) PSM with flexible frequency by patient (PSM/Flex/Pt). Mean differences (MDs) and risk ratios (RRs) with 95% confidence interval (CI) were estimated using frequentist network meta-analyses with a random-effects model. The certainty of evidence was evaluated using CINeMA (Confidence in Network Meta-Analysis). Sixteen RCTs involving 5,895 participants were included. When compared with usual care, time in therapeutic range was higher in PSM/High/Pt and PST/High/e-Health with MD [95% CI] of 7.67% [0.26-15.08] and 5.65% [0.04-11.26], respectively. The certainty of evidence was rated as moderate for these findings. The risk of thromboembolic events was lower in the PSM/Flex/Pt group when compared with PST/High/e-Health (RR: 0.39 [0.20-0.77]) and usual care (RR: 0.38 [0.17-0.88]) with low and very low level of evidence, respectively. There was no significant difference in the proportion of international normalized ratio (INR) values in range, major bleeding, and all-cause mortality among different self-care features. Patient self-care (either PST or PSM) by measuring INR values at least once weekly is more effective in controlling the INR level.

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  • 10.1002/14651858.cd013814
Acupuncture for chronic nonspecific low back pain.
  • Dec 11, 2020
  • The Cochrane database of systematic reviews
  • Jinglan Mu + 5 more

Acupuncture for chronic nonspecific low back pain.

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Comparing ovulation induction strategies for unexplained infertility: protocol for a systematic review and network meta-analysis.
  • Jan 28, 2026
  • BMJ open
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Unexplained infertility affects about 30% of couples seeking help for infertility, yet the optimal ovulation induction strategy remains largely unclear. Letrozole, clomiphene citrate and gonadotropins are widely used, alone or in combination, with or without intrauterine insemination (IUI), but evidence of comparative effectiveness and safety is inconsistent. Most reviews are restricted to pairwise comparisons or mixed infertility populations. This protocol describes a systematic review and network meta-analysis (NMA) to compare ovulation induction strategies specifically in unexplained infertility. Parallel-group randomised controlled trials (RCTs), including women aged 18-40 years with unexplained infertility, will be eligible. Interventions include letrozole, clomiphene citrate, gonadotropins, combination regimens and expectant management/ placebo, with or without IUI. The primary outcome will be live birth per woman randomised; if unavailable, ongoing or clinical pregnancy will be considered. Secondary outcomes include ovulation, multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome, ectopic pregnancy, neonatal outcomes, time to pregnancy, adverse events and cycle cancellation rates. Databases (MEDLINE/PubMed, Embase, Cochrane Library, Scopus and Web of Science), trial registry (ClinicalTrials.gov), and grey literature (postgraduate theses, conference abstracts and dissertations) will be searched from inception to September 2025. Two reviewers will independently screen, extract data and assess risk of bias (RoB-2). Pairwise random-effects meta-analyses will precede a Bayesian and frequentist NMA (if sufficient network). If feasible, component NMA will be performed to estimate marginal effects of drug and procedural components. Certainty of evidence will be assessed using the CINeMA framework (GRADE for NMA). Publication bias will be assessed using funnel plots and Egger's test, where feasible. No ethics approval is required. Findings will be published in peer-reviewed journals, presented at conferences and made available through open-access repositories. CRD420251145492. The review was registered prospectively; the review start date is 11 September 2025 and the anticipated end date is 3 March 2026.

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  • Cite Count Icon 1
  • 10.1001/jamapediatrics.2025.3099
Digital Health Interventions in Pediatric Perioperative Care
  • Sep 15, 2025
  • JAMA Pediatrics
  • Ziyue Luo + 13 more

Pediatric surgical patients often face considerable perioperative challenges, including anxiety and pain. Digital health interventions offer promise, but their efficacy remains uncertain. To compare the effects of digital health interventions in pediatric perioperative care. PubMed, Embase, Web of Science, CENTRAL, and CINAHL databases were searched up to March 1, 2025. Randomized clinical trials (RCTs) involving pediatric patients (aged ≤18 years) undergoing surgery with general anesthesia, where digital technology was used as a distraction intervention. A frequentist network meta-analysis with random-effects model was used to calculate standardized mean differences (SMDs) or mean differences (MDs) with 95% CIs. Interventions were ranked using P values, risk of bias assessed using the Cochrane risk of bias tool 2, and certainty of evidence rated using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Critical outcomes included pediatric preoperative anxiety, postoperative pain, emergence delirium, and induction compliance. Important but noncritical outcomes encompassed parental preoperative anxiety and postoperative satisfaction. Of 7734 RCTs screened, 49 were included involving 4535 youth (pooled mean age, 7.42 years; 95% CI, 6.85 to 7.99; 2989 [65.9%] male) with 7 interventions: virtual reality (VR), 2-dimensional (2D) games, 2D videos, interactive robots, midazolam, control (standard care), and enhanced control (eg, booklets). Compared to control, VR (SMD, -1.14; 95% CI, -1.54 to -0.74; moderate certainty), 2D videos (SMD, -1.08; 95% CI, -1.51 to -0.65; moderate certainty), 2D games (SMD, -1.02; 95% CI, -1.54 to -0.49; low certainty), and enhanced control (SMD, -0.83; 95% CI, -1.53 to -0.13; low certainty) reduced preoperative anxiety. VR (SMD, -1.09; 95% CI, -1.58 to -0.59; moderate certainty), 2D games (SMD, -0.87; 95% CI, -1.62 to -0.12; low certainty), and 2D videos (SMD, -0.56; 95% CI, -1.06 to -0.06; moderate certainty) reduced postoperative pain. VR showed the greatest effect on compliance (MD, -0.93; 95% CI, -1.62 to -0.24; moderate certainty). No significant differences compared to control. This network meta-analysis of RCTs found that VR, 2D videos, and 2D games significantly reduced pediatric perioperative anxiety and pain and improved induction compliance. These findings support the use of digital health interventions in pediatric perioperative care and their broader clinical adoption.

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  • 10.1136/bmj-2021-066785
Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials
  • Mar 9, 2022
  • BMJ
  • Maura Marcucci + 22 more

ObjectiveTo systematically compare the effect of direct oral anticoagulants and low molecular weight heparin for thromboprophylaxis on the benefits and harms to patients undergoing non-cardiac surgery.DesignSystematic review and network meta-analysis...

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