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The Cochrane Database of Systematic... 2002Evidence supports a role for the NMDA receptors in learning and memory. These can be modulated by the antibiotic D-cycloserine in such a way that the effect of the... (Review)
Review
BACKGROUND
Evidence supports a role for the NMDA receptors in learning and memory. These can be modulated by the antibiotic D-cycloserine in such a way that the effect of the excitatory transmitter substance glutamate is enhanced. A study on healthy subjects pretreated with scopolamine to mimic Alzheimer's disease showed a positive effect of D-cycloserine at low doses.
OBJECTIVES
To assess the efficacy and safety of D-cycloserine in patients with Alzheimer's disease.
SEARCH STRATEGY
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 14 June 2001 using the terms: cycloserine, D-cycloserine, Alzheimer*.
SELECTION CRITERIA
Randomized, double-blinded and unconfounded trials comparing D-cycloserine with a control treatment.
DATA COLLECTION AND ANALYSIS
Two larger and two smaller randomized controlled trials were identified. The clinical global impression scale was used in all studies and was a primary outcome measure.
MAIN RESULTS
It was not possible to extract the results from the first phases of the two crossover studies and therefore the meta-analyses are based on the two parallel group 6-month studies. There was no indication of a positive effect favouring D-cycloserine for the numbers showing improvement at 6 months as assessed by the Clinical Global Impression for any dose. The number of withdrawals for any reason before end of treatment at 6 months was significantly in favour of placebo (fewer withdrawals) compared with D-cycloserine for dose levels of 30 mg/day (OR 2.94, 95% CI 1.52, 5.70) and 100 mg/day (OR 3.23, 95% CI 1.67, 6.25). There was no significant difference between treatment, (2, 10, 30, 100, or 200 mg/day) and placebo for the number of withdrawals due to adverse events by six months.
REVIEWER'S CONCLUSIONS
The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.
Topics: Alzheimer Disease; Anti-Infective Agents, Urinary; Antibiotics, Antitubercular; Cycloserine; Humans; Randomized Controlled Trials as Topic
PubMed: 12076471
DOI: 10.1002/14651858.CD003153 -
PloS One 2015Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains poorly described.
METHODS
Systematic PubMed, Science Direct and Scopus searches for articles reporting phenotypic (liquid culture drug susceptibility testing or pyrazinamidase activity assays) and/or genotypic (polymerase chain reaction or DNA sequencing) PZA resistance. Global and regional summary estimates were obtained from random-effects meta-analysis, stratified by presence or risk of multidrug resistant TB (MDR-TB). Regional summary estimates were combined with regional WHO TB incidence estimates to determine the annual burden of PZA resistance. Information on single nucleotide polymorphisms (SNPs) in the pncA gene was aggregated to obtain a global summary.
RESULTS
Pooled PZA resistance prevalence estimate was 16.2% (95% CI 11.2-21.2) among all TB cases, 41.3% (29.0-53.7) among patients at high MDR-TB risk, and 60.5% (52.3-68.6) among MDR-TB cases. The estimated global burden is 1.4 million new PZA resistant TB cases annually, about 270,000 in MDR-TB patients. Among 1,815 phenotypically resistant isolates, 608 unique SNPs occurred at 397 distinct positions throughout the pncA gene.
INTERPRETATION
PZA resistance is ubiquitous, with an estimated one in six incident TB cases and more than half of all MDR-TB cases resistant to PZA globally. The diversity of SNPs across the pncA gene complicates the development of rapid molecular diagnostics. These findings caution against relying on PZA in current and future TB drug regimens, especially in MDR-TB patients.
Topics: Antitubercular Agents; Humans; Mycobacterium tuberculosis; Pyrazinamide; Tuberculosis, Multidrug-Resistant
PubMed: 26218737
DOI: 10.1371/journal.pone.0133869 -
American Journal of Nephrology 2016Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney transplant recipients. We conducted a meta-analysis of trials examining the bioavailability of generic (test) immunosuppressive drugs relative to their brand (reference) counterparts in healthy volunteers, based on the US Food and Drug Administration requirements for approval of generics, and their efficacy and safety in kidney transplant recipients.
METHODS
Eligible studies were identified in PubMed, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov, and conference abstracts.
RESULTS
Twenty crossover trials of healthy volunteers (n = 641) and 6 parallel-arm randomized controlled trials of kidney transplant recipients (n = 594) were identified. The 90% CI of the pooled test-to-reference drug ratio for maximum or peak plasma concentration (Cmax) and area under the plasma concentration time-curve from time 0 to time of last determinable concentration (AUC(0-t)) fell within the required range (0.80-1.25) for cyclosporine (Cmax 0.91; 90% CI 0.86-0.95; and AUC(0-t) 0.97; 90% CI 0.94-1.00), tacrolimus (Cmax 1.17; 90% CI 1.09-1.24; and AUC(0-t) 1.00; 90% CI 0.97-1.03) and mycophenolate mofetil (Cmax 0.98; 90% CI 0.96-1.01; and AUC(0-t) 1.00; 90% CI 0.99-1.01). In subgroup analyses, some generic cyclosporine formulations did not meet criteria for bioequivalence. No significant differences were observed in the time to maximum plasma concentration and terminal plasma half-life between generic and brand drugs. In parallel-arm trials, generic cyclosporine was non-inferior to brand counterpart in terms of acute allograft rejection, infections, and death.
CONCLUSIONS
Not all generic immunosuppressive drugs have similar relative bioavailability to their brand name counterparts. Evidence on their efficacy and safety is inconclusive. Tighter regulatory requirement for approval of generic drugs with narrow therapeutic index is needed.
Topics: Biological Availability; Cyclosporine; Drugs, Generic; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Tacrolimus; Therapeutic Equivalency
PubMed: 27576318
DOI: 10.1159/000449020 -
Arthritis Research & Therapy 2006Mycophenolate mofetil (MMF) is an immunosuppressant drug being used for induction and maintenance of remission of lupus nephritis in systemic lupus erythematosus.... (Meta-Analysis)
Meta-Analysis Review
Mycophenolate mofetil (MMF) is an immunosuppressant drug being used for induction and maintenance of remission of lupus nephritis in systemic lupus erythematosus. Evidence about its use was sought from full publications and abstracts of randomised trials and cohort studies by using a variety of search strategies. Efficacy and adverse event outcomes were sought. Five randomised trials enrolled patients with World Health Organization (WHO) class III, IV, or V (mostly IV) lupus nephritis, predominantly comparing MMF (1 to 3 g daily) with cyclophosphamide and steroid. Complete response and complete or partial response was significantly more frequent with MMF than with cyclophosphamide, with numbers needed to treat of 8 (95% confidence interval 4.3 to 60) to induce one additional complete or partial response, with wide confidence intervals. Death was reported less frequently with MMF (0.7%, 1 death in 152 patients) than with cyclophosphamide (7.8%, 12 deaths in 154 patients), with a number needed to treat to prevent (NNTp) one death of 14 (8 to 48). Hospital admission was also lower with MMF (1.7% versus 15%; NNTp 7.4 [4.8 to 16]). Serious infections, leucopaenia, amenorrhoea, and hair loss were all significantly less frequent with MMF than with cyclophosphamide, but diarrhoea was significantly more common with MMF. Ten of 18 cohort studies enrolled only patients with lupus nephritis (author-defined or WHO class III to V). Seven of these 10 reported that complete or partial response with MMF (mostly 1 or 2 g daily) with steroid occurred in 121/151 (80%) and that treatment failure or no response occurred in 30/151 (20%). Adverse events were generally similar in cohort studies with and without only patients with lupus nephritis. In all 18 cohorts, gastrointestinal adverse events (diarrhoea, nausea, vomiting) occurred in 30%, infection in 23%, and serious infection in 4.3%. Adverse event discontinuations occurred in 14% and lack of efficacy occurred in 10%. There was a single death with MMF, a mortality rate over the course of 1 year of approximately 0.2%. The results form a basis on which to plan future studies and provide a guide for the use of MMF in lupus nephritis until results of larger studies are available. At least one such study is under way.
Topics: Cohort Studies; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 17163990
DOI: 10.1186/ar2093 -
Revista Espanola de Salud Publica Dec 2022There are different socioeconomic variables which determine tuberculosis's epidemiology, diagnosis and treatment. The objective of this paper was to analize these... (Review)
Review
OBJECTIVE
There are different socioeconomic variables which determine tuberculosis's epidemiology, diagnosis and treatment. The objective of this paper was to analize these effects in the last years in Spain.
METHODS
A systematic review was conducted. Screened studies were original articles written in English or Spanish and published between 2007 and 2020. Searching was performed in Pubmed and Web of Science databases. STROBE criteria were followed to analyze studies's quality, and studies included in the review had 15 points or more.
RESULTS
23 articles were selected, and were classified in different topics. Foreigners's proportion with tuberculosis changed in different autonomous communities between 10%-50%. There were diagnostic delay for this group compared to natives. This group had higher incidence of resistance to isoniazid, but without a clear increase in multidrug resistance. There were less adherence to tuberculosis's treatment in case of immigration, drug addiction, HIV coinfection, or lack of family support. Under-reporting of tuberculosis cases varied between 18%-28%, and it was higher in cases of social marginality, HIV coinfection, Spanish nationality or male sex. There were also other social risk groups in which the diagnostic approach to tuberculosis was relevant, such as in schools and health centers. Tuberculosis was one of the most frequent HIV associated diseases, although screening tests were not performed in almost 18%, depending on the concurrence of social risk factors.
CONCLUSIONS
Tuberculosis's incidence, diagnosis, and treatment are influenced by a lot of social and economic factors, which determine the approach to this disease.
Topics: Male; Humans; Delayed Diagnosis; Spain; Socioeconomic Factors; Tuberculosis; Isoniazid
PubMed: 36458439
DOI: No ID Found -
Journal of the Chinese Medical... Feb 2018Anti-tuberculosis drug-induced liver injury (ATDILI) is a major safety concern in the treatment of tuberculosis (TB). The impact of chronic hepatitis C (CHC) infection... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anti-tuberculosis drug-induced liver injury (ATDILI) is a major safety concern in the treatment of tuberculosis (TB). The impact of chronic hepatitis C (CHC) infection on the risk of ATDILI is still controversial. We aimed to assess the influence of CHC infection on ATDILI through a systematic review and meta-analysis.
METHODS
We systemically reviewed all English-language literature in the major medical databases with the subject search terms "anti-tuberculosis drug-induced liver injury" and "anti-tuberculosis drug-induced hepatotoxicity". We then performed a systematic review and meta-analysis of the papers relevant to hepatitis C in qualified publications.
RESULTS
A total of 14 studies were eligible for analysis, which included 516 cases with ATDILI and 4301 controls without ATDILI. The pooled odds ratio (OR) of all studies for CHC infection to ATDILI was 3.21 (95% confidence interval (CI): 2.30-4.49). Subgroup analysis revealed that the CHC carriers had a higher risk of ATDILI than those without CHC both in Asians (OR = 2.96, 95% CI: 1.79-4.90) and Caucasians (OR = 4.07, 95% CI: 2.70-6.14), in those receiving standard four combination anti-TB therapy (OR = 2.94, 95% CI: 1.95-4.41) and isoniazid monotherapy (OR = 4.18, 95% CI: 2.36-7.40), in those with a strict definition of DILI (serum alanine aminotransferase [ALT] > 5 upper limit of normal value [ULN], OR = 2.59, 95% CI: 1.58-4.25) and a loose definition of DILI (ALT > 2 or 3 ULN, OR = 4.34, 95% CI: 2.96-6.37), and in prospective studies (OR = 4.16, 95% CI: 2.93-5.90) and case-control studies (OR = 2.43, 95% CI: 1.29-4.58).
CONCLUSION
This meta-analysis suggests that CHC infection may increase the risk of ATDILI. Regular liver tests are mandatory for CHC carriers under anti-TB therapy.
Topics: Antitubercular Agents; Chemical and Drug Induced Liver Injury; Disease Susceptibility; Hepatitis C, Chronic; Humans
PubMed: 29198550
DOI: 10.1016/j.jcma.2017.10.002 -
Genes Oct 2022Objective: The Beijing strain of Mycobacterium tuberculosis (MTB) is controversially presented as the predominant genotype and is more drug resistant to rifampicin and... (Meta-Analysis)
Meta-Analysis Review
Comparison on Major Gene Mutations Related to Rifampicin and Isoniazid Resistance between Beijing and Non-Beijing Strains of : A Systematic Review and Bayesian Meta-Analysis.
Objective: The Beijing strain of Mycobacterium tuberculosis (MTB) is controversially presented as the predominant genotype and is more drug resistant to rifampicin and isoniazid compared to the non-Beijing strain. We aimed to compare the major gene mutations related to rifampicin and isoniazid drug resistance between Beijing and non-Beijing genotypes, and to extract the best evidence using the evidence-based methods for improving the service of TB control programs based on genetics of MTB. Method: Literature was searched in Google Scholar, PubMed and CNKI Database. Data analysis was conducted in R software. The conventional and Bayesian random-effects models were employed for meta-analysis, combining the examinations of publication bias and sensitivity. Results: Of the 8785 strains in the pooled studies, 5225 were identified as Beijing strains and 3560 as non-Beijing strains. The maximum and minimum strain sizes were 876 and 55, respectively. The mutations prevalence of rpoB, katG, inhA and oxyR-ahpC in Beijing strains was 52.40% (2738/5225), 57.88% (2781/4805), 12.75% (454/3562) and 6.26% (108/1724), respectively, and that in non-Beijing strains was 26.12% (930/3560), 28.65% (834/2911), 10.67% (157/1472) and 7.21% (33/458), separately. The pooled posterior value of OR for the mutations of rpoB was 2.72 ((95% confidence interval (CI): 1.90, 3.94) times higher in Beijing than in non-Beijing strains. That value for katG was 3.22 (95% CI: 2.12, 4.90) times. The estimate for inhA was 1.41 (95% CI: 0.97, 2.08) times higher in the non-Beijing than in Beijing strains. That for oxyR-ahpC was 1.46 (95% CI: 0.87, 2.48) times. The principal patterns of the variants for the mutations of the four genes were rpoB S531L, katG S315T, inhA-15C > T and oxyR-ahpC intergenic region. Conclusion: The mutations in rpoB and katG genes in Beijing are significantly more common than that in non-Beijing strains of MTB. We do not have sufficient evidence to support that the prevalence of mutations of inhA and oxyR-ahpC is higher in non-Beijing than in Beijing strains, which provides a reference basis for clinical medication selection.
Topics: Isoniazid; Mycobacterium tuberculosis; Rifampin; Antitubercular Agents; Bayes Theorem; Microbial Sensitivity Tests; Bacterial Proteins; Mutation; DNA, Intergenic
PubMed: 36292734
DOI: 10.3390/genes13101849 -
BMC Infectious Diseases Jun 2016In 2014 only 50 % of multidrug-resistant tuberculosis (MDR-TB) patients achieved a successful treatment outcome. With limited options for medical treatment, surgery has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In 2014 only 50 % of multidrug-resistant tuberculosis (MDR-TB) patients achieved a successful treatment outcome. With limited options for medical treatment, surgery has re-emerged as an adjuvant therapeutic strategy. We conducted a systematic review and meta-analysis to assess the evidence for the effect of surgery as an adjunct to chemotherapy on outcomes of adults treated for MDR-TB.
METHODS
Databases and grey literature sources were searched using terms incorporating surgery and MDR-TB. No language or publication type limits were applied. Articles published pre-1990, without a comparator group, or reporting <10 surgical participants were excluded. Two-stage sifting in duplicate was employed. Data on WHO-defined treatment outcomes were abstracted into a standardised database. Study-level risk of bias was evaluated using standardised tools. Outcome-level evidence quality was assessed using GRADE. Forest plots were generated, random effects meta-analysis conducted, and heterogeneity assessed using the I(2) statistic.
RESULTS
Of 1024 unique citations identified, 62 were selected for full-text review and 15 retained for inclusion. A further four articles were included after bibliography/citation searching, and one additional unpublished manuscript was identified, giving 20 articles for final inclusion. Six were meta-analyses/systematic reviews and 14 were primary research articles (observational studies). From the 14 primary research articles, a successful outcome (cured/treatment completed) was reported for 81.9 % (371/453) and 59.7 % (1197/2006) in the surgical and non-surgical group respectively, giving a summary odds ratio of 2.62 (95 % confidence interval 1.94-3.54). Loss to follow-up and treatment failure were lower in the surgery group (both p = 0.01). Overall GRADE quality of evidence for all outcomes considered was "very low".
CONCLUSIONS
This meta-analysis suggests that surgery as an adjunct to chemotherapy is associated with improved treatment outcomes in MDR-TB patients. However, inherent limitations in observational study design, insufficient reporting, and lack of adjustment for confounders, led to grading of the evidence as very low quality. Data on rationale for surgical referral, subsequent outcomes and resource-limited settings are scarce, precluding evidence-based recommendations on the suitability of surgery by patient characteristics or setting. It is hoped that highlighted methodological and reporting gaps will encourage improved design and reporting of future surgical studies for MDR-TB.
Topics: Antitubercular Agents; Humans; Odds Ratio; Pneumonectomy; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 27283524
DOI: 10.1186/s12879-016-1585-0 -
BMC Public Health Mar 2015Prevalence of multidrug resistant tuberculosis (MDR-TB), defined as in vitro resistance to both rifampicin and isoniazid with or without resistance to other TB drugs, in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prevalence of multidrug resistant tuberculosis (MDR-TB), defined as in vitro resistance to both rifampicin and isoniazid with or without resistance to other TB drugs, in sub-Saharan Africa (SSA) is reportedly low compared to other regions. These estimates are based on data reported to the World Health Organization (WHO) on drug resistance surveys, which may suffer from a reporting bias. We set out to evaluate the variation in prevalence of drug resistant tuberculosis (DR-TB) and its determinants across SSA countries among new and previously treated TB patients.
METHODS
The aim was to perform a systematic review and meta-analysis of DR-TB prevalence and associated risk factors in SSA. PubMed, EMBASE, Cochrane and bibliographies of DR-TB studies were searched. Surveys at national or sub-national level, with reported DR-TB prevalence (or sufficient data to calculate a prevalence) to isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and streptomycin (SM) conducted in SSA excluding the Republic of South Africa, published between 2003 and 2013 with no language restriction were considered. Two authors searched and reviewed the studies for eligibility and extracted the data in pre-defined forms. Forest plots of all prevalence estimates by resistance outcome were performed. Summary estimates were calculated using random effects models, when appropriate. Associations between any DR-TB and MDR-TB with potential risk factors were examined through subgroup analyses stratified by new and previously treated patients.
RESULTS
A total of 726 studies were identified, of which 27 articles fulfilled the inclusion criteria. Studies reported drug susceptibility testing (DST) results for a total of 13,465 new and 1,776 previously treated TB patients. Pooled estimate of any DR-TB prevalence among the new cases was 12.6% (95% CI 10.6-15.0) while for MDR-TB this was 1.5% (95% CI 1.0-2.3). Among previously treated patients, these were 27.2% (95% CI 21.4-33.8) and 10.3% (95% CI 5.8-17.4%), respectively. DR-TB (any and MDR-TB) did not vary significantly with respect to study characteristics.
CONCLUSIONS
The reported prevalence of DR-TB in SSA is low compared to WHO estimates. MDR-TB in this region does not seem to be driven by the high HIV prevalence rates.
Topics: Africa South of the Sahara; Antitubercular Agents; Bacteriological Techniques; Ethambutol; Humans; Isoniazid; Prevalence; Rifampin; Risk Factors; Streptomycin; Tuberculosis, Multidrug-Resistant; World Health Organization
PubMed: 25880829
DOI: 10.1186/s12889-015-1614-8 -
International Journal of Infectious... Sep 2020To assess poor treatment outcomes and their predictors among drug-resistant tuberculosis patients treated in Ethiopia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess poor treatment outcomes and their predictors among drug-resistant tuberculosis patients treated in Ethiopia.
METHODS
Data were searched from both electronic databases and other sources. From the whole search, 404 articles were reviewed and 17 articles that fulfilled the inclusion criteria were included in the analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed and Joanna Briggs Institute Critical Appraisal checklist was used for assessing the quality. Risk of bias was assessed using forest plot and Egger's regression test. Data were analyzed using STATA version 15 and Review Manager Software version 5.3.
RESULTS
The overall pooled proportion of poor treatment outcome and mortality was 17.86% and 15.13% respectively. The incidence density rate of poor treatment outcome and mortality was 10.41/1000 person-months and 9.28/1000 person-months respectively. Survival status and successful treatment outcomes were 76.97% and 63.82% respectively. HIV positivity, non-HIV comorbidities, clinical complications, extrapulmonary involvement, undernutrition, anemia, treatment delay, lower body weight, and older age were the predictors of poor treatment outcome.
CONCLUSION
Better survival and treatment success rates were noted in Ethiopia as compared to the global average. The majority of the poor treatment outcomes occurred within the intensive phase. Early initiation of anti-tuberculosis treatment would be important for successful treatment outcomes.
Topics: Adolescent; Adult; Antitubercular Agents; Ethiopia; Female; Humans; Male; Time-to-Treatment; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 32645375
DOI: 10.1016/j.ijid.2020.05.087