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Gastroenterology Research Dec 2020(HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy or bismuth-based quadruple therapy is usually considered the first-line...
BACKGROUND
(HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy or bismuth-based quadruple therapy is usually considered the first-line treatment, however with around 30% failure rate for both regimens. Drug resistance of clarithromycin and metronidazole is a growing concern in some parts of the world. Therefore, there is a need for effective eradication regimen for HP. Nitazoxanide, a bactericidal thiazolide antibiotic, has been shown to be effective in HP infection. We conducted a systematic review and meta-analysis to evaluate the efficacy of nitazoxanide-based regimen for the eradication of HP.
METHODS
We have searched PubMed, Embase, Ovid Medline and Cochrane library database from inception to December 9, 2020 to identify studies that utilized nitazoxanide in the treatment regimen for HP eradication. Our primary outcome was pooled eradication rate of HP.
RESULTS
Thirteen studies including 1,028 patients met our inclusion criteria and were analyzed in a meta-analysis. HP eradication was successful in 867 patients with a pooled eradication rate of 86% (95% confidence interval (CI): 79-90%) with 84% heterogeneity. A subgroup analysis that included 230 patients who failed other prior eradication regimens revealed a pooled eradication rate of 85% (95% CI: 69-94%) without heterogeneity. In a subgroup analysis, highest eradication rates were achieved with levofloxacin, doxycycline, nitazoxanide and proton pump inhibitor with a pooled eradication rate of 92% (88-95%).
CONCLUSION
Nitazoxanide-based regimen is safe and effective in the eradication of HP infection. It is also successful as a salvage therapy in patients who have failed prior treatments.
PubMed: 33447305
DOI: 10.14740/gr1342 -
The Japanese Dental Science Review Nov 2020This review aimed to evaluate the effects of the local delivery of antibiotics incorporated in implant surfaces on some quantitative parameters of bone formation. (Review)
Review
PURPOSE
This review aimed to evaluate the effects of the local delivery of antibiotics incorporated in implant surfaces on some quantitative parameters of bone formation.
MATERIALS AND METHODS
An electronic search was undertaken in three databases (PubMed, Scopus, Embase) in addition to hand searching. The search was limited to animal experiments using endosseous implants combined with localized antibiotics release. Meta-analyses were performed for the percentages of bone volume (BV) and bone-to-implant contact (BIC).
RESULTS
Nine studies met the inclusion criteria. Several methods were identified for local delivery of antibiotics at the bone-implant interface, but the most commonly used method was by coating (incorporating the implant surface with the antibiotic agents). Different antibiotic agents were used, namely bacitracin, doxycycline, enoxacin, gentamicin, minocycline, tobramycin, and vancomycin. There was no statistically significant difference in the percentage of BIC between implants with or without localized antibiotic release ( = 0.59). The meta-analysis revealed higher BV around implants coated with antibiotics compared to control groups (without antibiotics) ( < 0.01).
CONCLUSION
It is suggested that the local administration of antibiotics around implants did not adversely affect the percentage of direct bone contact around implants, with a tendency for a slightly better bone formation around implants when combined with local administration of antibiotics. It is a matter of debate whether these in vivo results will have the same effect in the clinical setting. However, the risk of bias of these studies may, to some extent, question the validity of these results.
PubMed: 33294060
DOI: 10.1016/j.jdsr.2020.09.003 -
Dental Research Journal 2020Scaling and root planing (SRP) for the treatment of periodontitis may be less effective in some patients. This study evaluated the effectiveness of local doxycycline as... (Review)
Review
Effect of locally delivered doxycycline as an adjunct to scaling and root planing in the treatment of periodontitis in smokers: A systematic review of randomized controlled trials with meta-analysis and trial sequential analysis.
BACKGROUND
Scaling and root planing (SRP) for the treatment of periodontitis may be less effective in some patients. This study evaluated the effectiveness of local doxycycline as an adjunct to SRP among smokers with periodontitis compared to SRP alone in randomized controlled trials (RCTs).
MATERIALS AND METHODS
For this systematic review and meta-analysis, PubMed and Scopus databases were searched till November 2018 for English publications. RCTs that compared the effect of local doxycycline adjunct to SRP among smokers with periodontitis were selected. Patient characteristics, disease characteristics, and outcome data on clinical attachment level (CAL) and periodontal probing depth at 1, 3- and 6-month follow-up was extracted. Quality of selected studies was assessed by the revised Cochrane Risk of Bias 2.0 tool. Random effects model and trial sequential analysis were performed. GRADE approach was used to assess the quality of evidence. > 0.05 was considered as statistically significant.
RESULTS
Five trials were included in the review. Local use of doxycycline as an adjunct to SRP was effective in gain of 1.1 mm (0.47-1.74, = 0.091) in CAL at 6 months calculated from two studies. The evidence was of low quality, and at least a total of 866 patients are required for conclusiveness.
CONCLUSION
Local doxycycline as an adjunct to SRP significantly improved clinical attachment in smokers with periodontitis and can be recommended. Studies are required with long-term follow-up and patient-related outcome data.
PubMed: 33282148
DOI: No ID Found -
Pharmaceutics Nov 2020This review aimed to rank the clinical efficacy of commercially available single-application local drug delivery and adjunctive agents (LDAs) compared with subgingival... (Review)
Review
This review aimed to rank the clinical efficacy of commercially available single-application local drug delivery and adjunctive agents (LDAs) compared with subgingival mechanical debridement (SMD) in nonsurgical periodontal therapy (NSPT). Randomized controlled clinical trials that compared LDAs against SMD alone or with placebo in adults (aged at least 18 years) diagnosed with periodontitis with a minimum of 6 months follow-up were included. A frequentist approach to random-effects network meta-analysis was implemented. The efficacies of the LDAs measured by probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain were reported as mean difference (MD) with 95% confidence intervals (CIs). The treatments were ranked according to their P-score. Four network meta-analyses suggested that sulfonic/sulfuric acid gel (PPD MD -1.13 mm, 95% CI -1.74 to -0.53, P-score 0.91; CAL MD -1.09 mm, 95% CI -1.58 to -0.61, P-score 0.95) and doxycycline hyclate gel (PPD MD -0.90 mm, 95% CI -1.50 to -0.30, P-score 0.93; CAL MD -0.84 mm, 95% CI -1.40 to -0.28, P-score 0.92) were the most effective in reducing PPD and gaining CAL in split-mouth and parallel studies, respectively (moderate certainty of evidence). LDAs have differing efficacies, but they present with possible clinical significance over SMD alone in NSPT.
PubMed: 33198248
DOI: 10.3390/pharmaceutics12111086 -
The Cochrane Database of Systematic... Nov 2020Systemic antimicrobials can be used as an adjunct to mechanical debridement (scaling and root planing (SRP)) as a non-surgical treatment approach to manage... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systemic antimicrobials can be used as an adjunct to mechanical debridement (scaling and root planing (SRP)) as a non-surgical treatment approach to manage periodontitis. A range of antibiotics with different dosage and combinations are documented in the literature. The review follows the previous classification of periodontitis as all included studies used this classification.
OBJECTIVES
To assess the effects of systemic antimicrobials as an adjunct to SRP for the non-surgical treatment of patients with periodontitis.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases to 9 March 2020: Cochrane Oral Health's Trials Register, CENTRAL, MEDLINE, and Embase. The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) which involved individuals with clinically diagnosed untreated periodontitis. Trials compared SRP with systemic antibiotics versus SRP alone/placebo, or with other systemic antibiotics.
DATA COLLECTION AND ANALYSIS
We selected trials, extracted data, and assessed risk of bias in duplicate. We estimated mean differences (MDs) for continuous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 45 trials conducted worldwide involving 2664 adult participants. 14 studies were at low, 8 at high, and the remaining 23 at unclear overall risk of bias. Seven trials did not contribute data to the analysis. We assessed the certainty of the evidence for the 10 comparisons which reported long-term follow-up (≥ 1 year). None of the studies reported data on antimicrobial resistance and patient-reported quality of life changes. Amoxicillin + metronidazole + SRP versus SRP in chronic/aggressive periodontitis: the evidence for percentage of closed pockets (MD -16.20%, 95% CI -25.87 to -6.53; 1 study, 44 participants); clinical attachment level (CAL) (MD -0.47 mm, 95% CI -0.90 to -0.05; 2 studies, 389 participants); probing pocket depth (PD) (MD -0.30 mm, 95% CI -0.42 to -0.18; 2 studies, 389 participants); and percentage of bleeding on probing (BOP) (MD -8.06%, 95% CI -14.26 to -1.85; 2 studies, 389 participants) was of very low certainty. Only the results for closed pockets and BOP showed a minimally important clinical difference (MICD) favouring amoxicillin + metronidazole + SRP. Metronidazole + SRP versus SRP in chronic/aggressive periodontitis: the evidence for percentage of closed pockets (MD -12.20%, 95% CI -29.23 to 4.83; 1 study, 22 participants); CAL (MD -1.12 mm, 95% CI -2.24 to 0; 3 studies, 71 participants); PD (MD -1.11 mm, 95% CI -2.84 to 0.61; 2 studies, 47 participants); and percentage of BOP (MD -6.90%, 95% CI -22.10 to 8.30; 1 study, 22 participants) was of very low certainty. Only the results for CAL and PD showed an MICD favouring the MTZ + SRP group. Azithromycin + SRP versus SRP for chronic/aggressive periodontitis: we found no evidence of a difference in percentage of closed pockets (MD 2.50%, 95% CI -10.19 to 15.19; 1 study, 40 participants); CAL (MD -0.59 mm, 95% CI -1.27 to 0.08; 2 studies, 110 participants); PD (MD -0.77 mm, 95% CI -2.33 to 0.79; 2 studies, 110 participants); and percentage of BOP (MD -1.28%, 95% CI -4.32 to 1.76; 2 studies, 110 participants) (very low-certainty evidence for all outcomes). Amoxicillin + clavulanate + SRP versus SRP for chronic periodontitis: the evidence from 1 study, 21 participants for CAL (MD 0.10 mm, 95% CI -0.51 to 0.71); PD (MD 0.10 mm, 95% CI -0.17 to 0.37); and BOP (MD 0%, 95% CI -0.09 to 0.09) was of very low certainty and did not show a difference between the groups. Doxycycline + SRP versus SRP in aggressive periodontitis: the evidence from 1 study, 22 participants for CAL (MD -0.80 mm, 95% CI -1.49 to -0.11); and PD (MD -1.00 mm, 95% CI -1.78 to -0.22) was of very low certainty, with the doxycycline + SRP group showing an MICD in PD only. Tetracycline + SRP versus SRP for aggressive periodontitis: we found very low-certainty evidence of a difference in long-term improvement in CAL for the tetracycline group (MD -2.30 mm, 95% CI -2.50 to -2.10; 1 study, 26 participants). Clindamycin + SRP versus SRP in aggressive periodontitis: we found very low-certainty evidence from 1 study, 21 participants of a difference in long-term improvement in CAL (MD -1.70 mm, 95% CI -2.40 to -1.00); and PD (MD -1.80 mm, 95% CI -2.47 to -1.13) favouring clindamycin + SRP. Doxycycline + SRP versus metronidazole + SRP for aggressive periodontitis: there was very low-certainty evidence from 1 study, 27 participants of a difference in long-term CAL (MD 1.10 mm, 95% CI 0.36 to 1.84); and PD (MD 1.00 mm, 95% CI 0.30 to 1.70) favouring metronidazole + SRP. Clindamycin + SRP versus metronidazole + SRP for aggressive periodontitis: the evidence from 1 study, 26 participants for CAL (MD 0.20 mm, 95% CI -0.55 to 0.95); and PD (MD 0.20 mm, 95% CI -0.38 to 0.78) was of very low certainty and did not show a difference between the groups. Clindamycin + SRP versus doxycycline + SRP for aggressive periodontitis: the evidence from 1 study, 23 participants for CAL (MD -0.90 mm, 95% CI -1.62 to -0.18); and PD (MD -0.80 mm, 95% CI -1.58 to -0.02) was of very low certainty and did not show a difference between the groups. Most trials testing amoxicillin, metronidazole, and azithromycin reported adverse events such as nausea, vomiting, diarrhoea, mild gastrointestinal disturbances, and metallic taste. No serious adverse events were reported.
AUTHORS' CONCLUSIONS
There is very low-certainty evidence (for long-term follow-up) to inform clinicians and patients if adjunctive systemic antimicrobials are of any help for the non-surgical treatment of periodontitis. There is insufficient evidence to decide whether some antibiotics are better than others when used alongside SRP. None of the trials reported serious adverse events but patients should be made aware of the common adverse events related to these drugs. Well-planned RCTs need to be conducted clearly defining the minimally important clinical difference for the outcomes closed pockets, CAL, PD, and BOP.
Topics: Adult; Aggressive Periodontitis; Anti-Bacterial Agents; Bias; Chemotherapy, Adjuvant; Chronic Periodontitis; Confidence Intervals; Dental Prophylaxis; Humans; Randomized Controlled Trials as Topic
PubMed: 33197289
DOI: 10.1002/14651858.CD012568.pub2 -
Journal of Neurochemistry Mar 2021The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization...
The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate-limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence-specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac-conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood-brain barrier, but its half-life is short and liver failure a potential side effect. Amyloid-directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR-amyloidosis has become a model disease for pathophysiology-based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood-brain barrier permeability.
Topics: Amyloid; Amyloidosis, Familial; Animals; Gene Knockdown Techniques; Humans; Prealbumin
PubMed: 33155274
DOI: 10.1111/jnc.15233 -
Journal Der Deutschen Dermatologischen... Jan 2021Low-dose doxycycline (SDD) is an antimicrobial agent that appears to improve common inflammatory skin diseases. Few data are available regarding the overall... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Low-dose doxycycline (SDD) is an antimicrobial agent that appears to improve common inflammatory skin diseases. Few data are available regarding the overall effectiveness, appropriate length of treatment and optimal patient selection for rosacea. We therefore reviewed the efficacy of sub-antimicrobial doses of SDD in papulopustular rosacea (PPR) and aimed to determine the most suitable patients for this approach.
METHODS
From July to September 2019, we carried out a comprehensive search of literature from five databases, using a combination of "rosacea" AND "doxycycline".
RESULTS
Our search yielded 532 potentially relevant studies. Our meta-analysis showed no significant difference between SDD and a comparator (RR: 1.12, 95 % CI: 0.78-1.62, I = 86 %). Subgroup analysis of studies comparing doxycycline with placebo yielded a clear difference in favor of doxycycline (RR: 1.45, 95 % CI: 1.22-1.72, I = 31 %), while subgroup analysis of studies comparing active drugs revealed no difference between interventions (RR: 0.52, 95 % CI: 0.17-1.63, I = 90 %).
CONCLUSIONS
There is strong evidence that SDD is more effective than placebo. However, other drugs such as minocycline or isotretinoin have shown outcomes at least similar to that of SDD. We suggest that the anti-inflammatory properties of SDD may be of more value for mild cases of rosacea than for moderate to severe cases, for which higher (antimicrobial) doses of doxycycline may be a more suitable choice.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Doxycycline; Humans; Rosacea
PubMed: 32989925
DOI: 10.1111/ddg.14247 -
Journal of the American Heart... Oct 2020Background The emergence of specific therapies for transthyretin cardiac amyloidosis (CA) warrants the need for a systematic review of the literature. Methods and...
Background The emergence of specific therapies for transthyretin cardiac amyloidosis (CA) warrants the need for a systematic review of the literature. Methods and Results A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was performed on MEDLINE, PubMed, and Embase databases on November 29, 2019. Studies were selected based on the following predefined eligibility criteria: English-language randomized controlled trials (RCTs), non-RCTs, or observational studies, which included adult patients with variant/wild-type transthyretin-CA, assessed specific therapies for transthyretin-CA, and reported cardiovascular outcomes. Relevant data were extracted to a predefined template. Quality assessment was based on National Institute for Health and Care Excellence recommendations (RCTs) or a checklist by Downs and Black (non-RCTs). From 1203 records, 24 publications were selected, describing 4 RCTs (6 publications) and 16 non-RCTs (18 publications). Tafamidis was shown to significantly improve all-cause mortality and cardiovascular hospitalizations and reduce worsening in 6-minute walk test, Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in variant/wild-type transthyretin-CA. Patisiran showed promising results in a subgroup analysis of patients with variant transthyretin-CA, which have to be confirmed in RCTs. Inotersen showed conflicting results on cardiac imaging parameters. The one study on AG10 had only a 1-month duration and cardiovascular end points were exploratory and limited to cardiac biomarkers. Limited evidence from noncomparative single-arm small non-RCTs existed for diflunisal, epigallocatechin-3-gallate (green tea extract), and doxycycline+tauroursodeoxycholic acid/ursodeoxycholic acid. Conclusions This systematic review of the literature supports the use of tafamidis in wild-type and variant transthyretin-CA. Novel therapeutic targets including transthyretin gene silencers are currently under investigation.
Topics: Amyloid Neuropathies, Familial; Benzoxazoles; Cardiomyopathies; Cardiovascular Agents; Genetic Therapy; Humans
PubMed: 32969287
DOI: 10.1161/JAHA.120.016614 -
BMJ Open Sep 2020The gut microbiota influences many aspects of human health. We investigated the magnitude and duration of changes in gut microbiota in response to antibiotics commonly... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The gut microbiota influences many aspects of human health. We investigated the magnitude and duration of changes in gut microbiota in response to antibiotics commonly prescribed in UK primary care.
METHODS
We searched MEDLINE, EMBASE and AMED, all years up to May 2020 including all study designs, collecting and analysing data on the effect of antibiotics prescribed for respiratory and urinary tract infections. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane standard methods. Risk of bias was evaluated using the Critical Appraisal Skills Programme. Narrative synthesis was used to report the themes emerging from the data.
MAIN OUTCOME MEASURES
Primary outcomes were antibiotic-induced changes in the composition and/or diversity of the gut microbiota. Secondary outcome was the time for the microbiota to return to baseline.
RESULTS
Thirty-one articles with low or unclear risk of bias showed that antibiotics impact the gut microbiota by causing rapid and diminished levels of bacterial diversity and changes in relative abundances. After cessation of treatment, gut bacteria recover, in most individuals, to their baseline state within a few weeks. Some studies suggested longer term effects from 2 to 6 months. Considerable heterogeneity in methodology makes the studies prone to biases and other confounding factors. Doxycycline was associated with a marked short-term decrease in diversity. Clarithromycin decreased the populations of Enterobacteria, and the anaerobic bacteria sp and sp in numbers and diversity for up to 5 weeks. Phenoxymethylpenicillin, nitrofurantoin and amoxicillin had very little effect on the gut microbiome.
CONCLUSIONS
Despite substantial heterogeneity of the studies and small sample sizes, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota. Larger population-based studies are needed to fully understand how antibiotics modulate the microbiota, and to determine if these are associated with (longer term) health consequences.
PROSPERO REGISTRATION NUMBER
CRD42017073750.
Topics: Amoxicillin; Anti-Bacterial Agents; Gastrointestinal Microbiome; Humans; Primary Health Care; United Kingdom
PubMed: 32958481
DOI: 10.1136/bmjopen-2019-035677 -
BMC Oral Health Aug 2020Recurrent aphthous stomatitis (RAS) is a highly prevalent oral mucosal disease. The management of RAS is quite challenging, and as yet, there is no definitive cure. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recurrent aphthous stomatitis (RAS) is a highly prevalent oral mucosal disease. The management of RAS is quite challenging, and as yet, there is no definitive cure. The present systematic review and meta-analysis assessed the efficacy of a single application of topical doxycycline for the management of RAS.
METHODS
A comprehensive online search of PubMed, Scopus, Embase, and Web of Science databases was conducted to identify all relevant studies published up to March 31, 2019. All randomized clinical trials that assessed the efficacy of a single application of topical doxycycline in the management of RAS were included. Primary outcome measures were pain scores and/or healing time, while secondary outcomes included the associated side effects. RevMan 5.3 software was used for data analysis.
RESULTS
Five clinical trials fulfilled the eligibility criteria, three of which were included in the meta-analysis. All of the included studies found doxycycline effective in alleviating signs and symptoms of RAS. The results of the pooled 3 studies revealed a statistically significant decrease in the healing time in favor of the doxycycline group as compared to the control groups (I = 51%; MD: -1.77, 95% CI: - 2.11, - 1.42, P <0.00001); however, the results showed no significant differences between doxycycline and control groups with regard to pain reduction (I = 96%; MD: -1.28, 95% CI: - 2.83, 0.27; P = 0.11).
CONCLUSION
Although still inconclusive, the available evidence suggests that a single application of topical doxycycline might be effective for reducing signs and symptoms of RAS. However, owing to the limited number of the included studies, further well-designed clinical trials with adequate sample sizes are required to discern the clinical efficacy of topical doxycycline in patients with RAS.
Topics: Doxycycline; Humans; Mouth Diseases; Pain; Stomatitis, Aphthous; Treatment Outcome
PubMed: 32831085
DOI: 10.1186/s12903-020-01220-5