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BMC Oral Health Sep 2019To compare the effectiveness of systemic doxycycline as an adjunct to scaling and root planing (SRP) with SRP alone in improving periodontal clinical attachment level... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To compare the effectiveness of systemic doxycycline as an adjunct to scaling and root planing (SRP) with SRP alone in improving periodontal clinical attachment level and glycemic control in diabetic patients with periodontitis.
METHODS
Two independent reviewers (KY and SJ) screened two electronic databases, PubMed and Scopus, for randomized clinical trials on the use of systemic doxycycline as an adjunct to scaling and root planing in improving periodontal status and glycemic control in diabetic patients with periodontitis using predetermined selection criteria within a 3-month period. The reviewers independently did data screening, data selection, data extraction and risk of bias. Quality of studies involved was analysed using the revised Cochrane Risk of Bias 2.0. Weighted standard mean differences (SMD) and 95% confidence intervals were calculated using a random effects meta-analysis model. Publication bias was evaluated using funnel plot. Quality of evidence was evaluated by Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Electronic searches provided 1358 records and six studies were selected. The meta-analyses indicated that there was no statistically significant difference in the improvement of periodontal status with the use of systemic doxycycline as an adjunct for scaling and root planing (SRP). SMD of clinical attachment levels (- 0.22 [- 0.52, 0.08]) and HbA1c levels (- 0.13 [- 0.41, 0.15]) were calculated. Overall risk of bias is high in 2 out of 6 studies involved.
CONCLUSION
Systemic doxycycline when used in addition to scaling and root planing yields no significant improvement of clinical attachment levels for periodontal status and reduction of HbA1c levels in treatment of diabetic patients with periodontitis when comparing the test group to the control group.
Topics: Anti-Bacterial Agents; Dental Scaling; Diabetes Complications; Diabetes Mellitus; Doxycycline; Glycated Hemoglobin; Humans; Periodontal Attachment Loss; Periodontitis; Root Planing
PubMed: 31488125
DOI: 10.1186/s12903-019-0873-7 -
International Journal of Antimicrobial... Jul 2021Antibiotic consumption is a key driver of antimicrobial resistance (AR), particularly in low- and middle-income countries (LMICs) where risk factors for AR emergence and...
Antibiotic consumption is a key driver of antimicrobial resistance (AR), particularly in low- and middle-income countries (LMICs) where risk factors for AR emergence and spread are prevalent. However, the potential contribution of mass drug administration (MDA) and systematic drug administration (SDA) of antibiotics to AR spread is unknown. We conducted a systematic review to provide an overview of MDA/SDA in LMICs, including indications, antibiotics used and, if investigated, levels of AR over time. This systematic review is reported in accordance with the PRISMA statement. Of 2438 identified articles, 63 were reviewed: indications for MDA/SDA were various, and targeted populations were particularly vulnerable, including pregnant women, children, human immunodeficiency virus (HIV)-infected populations, and communities in outbreak settings. Available data suggest that MDA/SDA may lead to a significant increase in AR, especially following azithromycin administration. However, only 40% of studies evaluated AR. Integrative approaches that evaluate AR in addition to clinical outcomes are needed to understand the consequences of MDA/SDA implementation, combined with standardised AR surveillance for timely detection of AR emergence.
Topics: Amoxicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Ciprofloxacin; Developing Countries; Doxycycline; Drug Resistance, Microbial; Drug Utilization; Female; Humans; Mass Drug Administration; Pregnancy; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 34044108
DOI: 10.1016/j.ijantimicag.2021.106364 -
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 -
Frontiers in Medicine 2022We assessed nonconventional interventions that did not traditionally focus on increasing condom use and/or testing among men who have sex with men (MSM) and the evidence...
OBJECTIVES
We assessed nonconventional interventions that did not traditionally focus on increasing condom use and/or testing among men who have sex with men (MSM) and the evidence for these interventions.
METHODS
Guided by the Participants, Concept and Context (PCC) framework, we searched five online databases from inception to 9 August 2021 for original research on interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis in MSM. Two researchers screened titles and abstracts to assess eligibility, reviewed articles' full text and resolved discrepancies through discussion. We charted relevant study information, and the included studies were critically appraised.
RESULTS
Of 373 articles retrieved, 13 studies were included. These studies were conducted in Australia ( = 3), Belgium ( = 2), China ( = 3), the Netherlands ( = 1) and the US ( = 4). Two randomized controlled trials (RCTs) of doxycycline as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) reduced any STI incidence (gonorrhea, syphilis, or chlamydia), but only doxycycline PEP significantly reduced syphilis incidence. Six studies of interventions that facilitated self-collection, self-examination, and self-testing, found varied evidence for gonorrhea and/or syphilis prevention. Four RCTs and one single-arm trial examined the efficacy of mouthwash, but the evidence remains inconclusive on whether mouthwash use can prevent transmission between men.
CONCLUSION
We found evidence for doxycycline PEP in reducing syphilis incidence, evidence on the use of mouthwash to prevent gonorrhea transmission between men remains inconclusive. More evidence is needed for interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis.
PubMed: 36203757
DOI: 10.3389/fmed.2022.952476 -
Veterinary Parasitology May 2022According to the main Guidelines on canine heartworm disease (HWD) by the American and European Societies (i.e., AHS, ESDA, and ESCCAP), a correct diagnosis of...
According to the main Guidelines on canine heartworm disease (HWD) by the American and European Societies (i.e., AHS, ESDA, and ESCCAP), a correct diagnosis of Dirofilaria immitis infection should include the detection of circulating microfilariae in the whole blood and the adult antigens in serum or plasma sample. So far, scant data are available on laboratory abnormalities in dogs affected by HWD, although techniques including serum protein electrophoresis (SPEP) have proved to be useful for the diagnosis and monitoring of other vector-borne diseases, such as the canine leishmaniosis. Therefore, this study aims to evaluate the SPEP pattern in dogs naturally infected by D. immitis. Furthermore, a systematic review of the literature on this topic was carried out. Medical records from heartworm-positive dogs, of any sex, age, and breed and with available clinical examination and laboratory test results (i.e., complete blood count, serum biochemical profile, and SPEP) were retrospectively collected. If available, laboratory results obtained from dogs after treatment for HWD were also evaluated. When compared with the reference intervals, out of 30 dogs infected by D. immitis and enrolled, 63.3% (n = 19) had a lower percentage of albumin, and 80.0% (n = 24) had higher percentages of beta globulins, with beta-2, and especially beta-3 globulins the most frequently altered fractions. In terms of absolute values (g/dL), the proportion of dogs with hypoalbuminemia, and increased total globulin, alpha, beta- and gamma globulins were 4/30 (13.3%), 6/30 (20.0%), 2/30 (6.7%), 16/30 (53.3%) and 8/30 (26.7%), respectively. For 7 dogs, SPEP results evaluated three and six months after treatment with doxycycline (10 mg/kg BID for 4 weeks) were available. In these dogs a significant post-treatment increase in the percentage of albumin, alpha-2 globulin, and albumin/globulins ratio was observed, as well as a significant decrease both in the percentage and in the absolute value of total-, beta-, and beta-3 globulins. The systematic review of literature databases yielded a total of three studies that were considered eligible and included in the qualitative synthesis. This study provides novel information on SPEP alterations in dogs naturally infected by D. immitis. The evaluation of serum proteins and their electrophoretic pattern may represent an important diagnostic tool for a prompt and accurate diagnosis (e.g., differentiating infections in dogs sharing similar clinical signs and endemic in the same geographical area) and monitoring of HWD.
Topics: Albumins; Animals; Antigens, Helminth; Blood Proteins; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Electrophoresis; Globulins; Retrospective Studies
PubMed: 35597691
DOI: 10.1016/j.vetpar.2022.109720 -
Antimicrobial Resistance and Infection... Aug 2021There has been an increasing resistance rate to tetracyclines, the first line treatment for cholera disease caused by V. cholera strains, worldwide. The aim of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There has been an increasing resistance rate to tetracyclines, the first line treatment for cholera disease caused by V. cholera strains, worldwide. The aim of the present study was to determine the global status of resistance to this class of antibiotic among V. cholera isolates.
METHODS
For the study, electronic databases were searched using the appropriate keywords including: 'Vibrio', 'cholera', 'Vibrio cholerae', 'V. cholerae', 'resistance', 'antibiotic resistance', 'antibiotic susceptibility', 'antimicrobial resistance', 'antimicrobial susceptibility', 'tetracycline', and 'doxycycline'. Finally, after some exclusion, 52 studies from different countries were selected and included in the study and meta-analysis was performed on the collected data.
RESULTS
The average resistance rate for serogroup O1 to tetracycline and doxycycline was 50% and 28%, respectively (95% CI). A high level of heterogeneity (I > 50%, p-value < 0.05) was observed in the studies representing resistance to tetracycline and doxycycline in O1 and non-O1, non-O139 serogroups. The Begg's tests did not indicate the publication bias (p-value > 0.05). However, the Egger's tests showed some evidence of publication bias in the studies conducted on serogroup O1.
CONCLUSIONS
The results of the present study show that the overall resistance to tetracyclines is relatively high and prevalent among V. cholerae isolates, throughout the world. This highlights the necessity of performing standard antimicrobial susceptibility testing prior to treatment choice along with monitoring and management of antibiotic resistance patterns of V. cholerae strains in order to reduce the emergence and propagation of antibiotic resistant strains as well as the failure of treatment.
Topics: Anti-Bacterial Agents; Doxycycline; Serotyping; Tetracycline Resistance; Vibrio cholerae
PubMed: 34362438
DOI: 10.1186/s13756-021-00985-w -
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 -
Frontiers in Public Health 2021We provided a comprehensive evaluation of efficacy of available treatments for coronavirus disease 2019 (COVID-19). We searched for candidate COVID-19 studies in WHO... (Meta-Analysis)
Meta-Analysis
We provided a comprehensive evaluation of efficacy of available treatments for coronavirus disease 2019 (COVID-19). We searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database up to August 19, 2021. Randomized controlled trials for suspected or confirmed COVID-19 patients published on peer-reviewed journals were included, regardless of demographic characteristics. Outcome measures included mortality, mechanical ventilation, hospital discharge and viral clearance. Bayesian network meta-analysis with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs). Odds ratio (OR) was used as the summary measure for treatment effect. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by the treatment classifications. We identified 222 eligible studies with a total of 102,950 patients. Compared with the standard of care, imatinib, intravenous immunoglobulin and tocilizumab led to lower risk of death; baricitinib plus remdesivir, colchicine, dexamethasone, recombinant human granulocyte colony stimulating factor and tocilizumab indicated lower occurrence of mechanical ventilation; tofacitinib, sarilumab, remdesivir, tocilizumab and baricitinib plus remdesivir increased the hospital discharge rate; convalescent plasma, ivermectin, ivermectin plus doxycycline, hydroxychloroquine, nitazoxanide and proxalutamide resulted in better viral clearance. From the treatment class level, we found that the use of antineoplastic agents was associated with fewer mortality cases, immunostimulants could reduce the risk of mechanical ventilation and immunosuppressants led to higher discharge rates. This network meta-analysis identified superiority of several COVID-19 treatments over the standard of care in terms of mortality, mechanical ventilation, hospital discharge and viral clearance. Tocilizumab showed its superiority compared with SOC on preventing severe outcomes such as death and mechanical ventilation as well as increasing the discharge rate, which might be an appropriate treatment for patients with severe or mild/moderate illness. We also found the clinical efficacy of antineoplastic agents, immunostimulants and immunosuppressants with respect to the endpoints of mortality, mechanical ventilation and discharge, which provides valuable information for the discovery of potential COVID-19 treatments.
Topics: Bayes Theorem; COVID-19; Humans; Immunization, Passive; Network Meta-Analysis; Randomized Controlled Trials as Topic; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 34650951
DOI: 10.3389/fpubh.2021.729559 -
PLoS Neglected Tropical Diseases Oct 2021Scrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia. It is estimated that one billion people are at risk, with one million...
BACKGROUND
Scrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia. It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an individual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions.
METHODOLOGY/PRINCIPAL FINDINGS
We conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology. Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chloramphenicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women.
CONCLUSIONS/SIGNIFICANCE
There were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients.
Topics: Anti-Bacterial Agents; Azithromycin; Doxycycline; Feasibility Studies; Female; Humans; Male; Orientia tsutsugamushi; Scrub Typhus
PubMed: 34648517
DOI: 10.1371/journal.pntd.0009858 -
Open Forum Infectious Diseases Apr 2024Penicillin's long-standing role as the reference standard in syphilis treatment has led to global reliance. However, this dependence presents challenges, prompting the...
BACKGROUND
Penicillin's long-standing role as the reference standard in syphilis treatment has led to global reliance. However, this dependence presents challenges, prompting the need for alternative strategies. We performed a systematic literature review and meta-analysis to evaluate the efficacy of these alternative treatments against nonneurological syphilis.
METHODS
We searched MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane, Scopus, and Web of Science from database inception to 28 August 2023, and we included studies that compared penicillin or amoxicillin monotherapy to other treatments for the management of nonneurological syphilis. Our primary outcome was serological cure rates. Random-effect models were used to obtain pooled mean differences, and heterogeneity was assessed using the test.
RESULTS
Of 6478 screened studies, 27 met the inclusion criteria, summing 6710 patients. The studies were considerably homogeneous, and stratified analyses considering each alternative treatment separately revealed that penicillin monotherapy did not outperform ceftriaxone (pooled odds ratio, 1.66 [95% confidence interval, .97-2.84]; = 0%), azithromycin (0.92; [.73-1.18]; = 0%), or doxycycline (0.82 [.61-1.10]; = 1%) monotherapies with respect to serological conversion.
CONCLUSIONS
Alternative treatment strategies have serological cure rates equivalent to penicillin, potentially reducing global dependence on this antibiotic.
PubMed: 38595955
DOI: 10.1093/ofid/ofae142