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The Cochrane Database of Systematic... Sep 2017Tuberculous pericarditis can impair the heart's function and cause death; long term, it can cause the membrane to fibrose and constrict causing heart failure. In... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculous pericarditis can impair the heart's function and cause death; long term, it can cause the membrane to fibrose and constrict causing heart failure. In addition to antituberculous chemotherapy, treatments include corticosteroids, drainage, and surgery.
OBJECTIVES
To assess the effects of treatments for tuberculous pericarditis.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register (27 March 2017); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2017, Issue 2); MEDLINE (1966 to 27 March 2017); Embase (1974 to 27 March 2017); and LILACS (1982 to 27 March 2017). In addition we searched the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal using 'tuberculosis' and 'pericard*' as search terms on 27 March 2017. We searched ClinicalTrials.gov and contacted researchers in the field of tuberculous pericarditis. This is a new version of the original 2002 review.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-RCTs.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search outputs, evaluated study eligibility, assessed risk of bias, and extracted data; and we resolved any discrepancies by discussion and consensus. One trial assessed the effects of both corticosteroid and Mycobacterium indicus pranii treatment in a two-by-two factorial design; we excluded data from the group that received both interventions. We conducted fixed-effect meta-analysis and assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
Seven trials met the inclusion criteria; all were from sub-Saharan Africa and included 1959 participants, with 1051/1959 (54%) HIV-positive. All trials evaluated corticosteroids and one each evaluated colchicine, M. indicus pranii immunotherapy, and open surgical drainage. Four trials (1841 participants) were at low risk of bias, and three trials (118 participants) were at high risk of bias.In people who are not infected with HIV, corticosteroids may reduce deaths from all causes (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.09; 660 participants, 4 trials, low certainty evidence) and the need for repeat pericardiocentesis (RR 0.85, 95% CI 0.70 to 1.04; 492 participants, 2 trials, low certainty evidence). Corticosteroids probably reduce deaths from pericarditis (RR 0.39, 95% CI 0.19 to 0.80; 660 participants, 4 trials, moderate certainty evidence). However, we do not know whether or not corticosteroids have an effect on constriction or cancer among HIV-negative people (very low certainty evidence).In people living with HIV, only 19.9% (203/1959) were on antiretroviral drugs. Corticosteroids may reduce constriction (RR 0.55, 0.26 to 1.16; 575 participants, 3 trials, low certainty evidence). It is uncertain whether corticosteroids have an effect on all-cause death or cancer (very low certainty evidence); and may have little or no effect on repeat pericardiocentesis (RR 1.02, 0.89 to 1.18; 517 participants, 2 trials, low certainty evidence).For colchicine among people living with HIV, we found one small trial (33 participants) which had insufficient data to make any conclusions about any effects on death or constrictive pericarditis.Irrespective of HIV status, due to very low certainty evidence from one trial, it is uncertain whether adding M. indicus pranii immunotherapy to antituberculous drugs has an effect on any outcome.Open surgical drainage for effusion may reduce repeat pericardiocentesis In HIV-negative people (RR 0.23, 95% CI 0.07 to 0.76; 122 participants, 1 trial, low certainty evidence) but may make little or no difference to other outcomes. We did not find an eligible trial that assessed the effects of open surgical drainage in people living with HIV.The review authors found no eligible trials that examined the length of antituberculous treatment needed nor the effects of other adjunctive treatments for tuberculous pericarditis.
AUTHORS' CONCLUSIONS
For HIV-negative patients, corticosteroids may reduce death. For HIV-positive patients not on antiretroviral drugs, corticosteroids may reduce constriction. For HIV-positive patients with good antiretroviral drug viral suppression, clinicians may consider the results from HIV-negative patients more relevant.Further research may help evaluate percutaneous drainage of the pericardium under local anaesthesia, the timing of pericardiectomy in tuberculous constrictive pericarditis, and new antibiotic regimens.
Topics: Adrenal Cortex Hormones; Antitubercular Agents; Cause of Death; Colchicine; Drainage; HIV Seronegativity; HIV Seropositivity; Humans; Immunotherapy; Pericardiectomy; Pericarditis, Tuberculous; Pericardium; Randomized Controlled Trials as Topic
PubMed: 28902412
DOI: 10.1002/14651858.CD000526.pub2 -
The Cochrane Database of Systematic... Sep 2018Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.
OBJECTIVES
To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.
SEARCH METHODS
We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.
SELECTION CRITERIA
Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test).
DATA COLLECTION AND ANALYSIS
For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.
MAIN RESULTS
We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.
AUTHORS' CONCLUSIONS
Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.
Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chloramphenicol; Doxycycline; Humans; Macrolides; Randomized Controlled Trials as Topic; Rifampin; Scrub Typhus; Tetracycline
PubMed: 30246875
DOI: 10.1002/14651858.CD002150.pub2 -
Archives of Dermatological Research Jun 2024Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains... (Review)
Review
Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains uncertain due to limited systematic evidence. Our objective was to analyze antistreptococcal therapies' effectiveness in improving psoriasis. We conducted a systematic review following PRISMA guidelines, evaluating antistreptococcal treatment efficacy in psoriasis patients from PubMed, Scopus, and Embase databases until August 14, 2022. Eligible studies included psoriasis patients undergoing antistreptococcal therapy, regardless of demographics or psoriasis type. 50 studies (1778 patients) were analyzed, with penicillins/aminopenicillins as the most studied antibiotics (21 studies), showing mixed outcomes, some reporting significant improvement in guttate psoriasis, while others showed no significant difference. Rifampin demonstrated positive results in most of ten studies, and macrolides showed varying effectiveness in two studies. Tonsillectomy in 14 studies (409 patients) mainly focusing on guttate and chronic plaque psoriasis showed positive outcomes, indicating improved symptoms and quality of life. Limitations include heterogeneous studies, sampling bias, and quality of evidence. This systematic review reveals limited and varied evidence for systemic antibiotic therapy efficacy in psoriasis treatment, while tonsillectomy emerges as a potentially beneficial antistreptococcal option, urging further well-designed, controlled studies with larger sample sizes and standardized protocols for better comparisons.
Topics: Humans; Psoriasis; Anti-Bacterial Agents; Streptococcal Infections; Treatment Outcome; Quality of Life; Penicillins; Rifampin
PubMed: 38850287
DOI: 10.1007/s00403-024-03051-8 -
Clinical Rheumatology Feb 2024Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may resist several lines of treatment. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of mycophenolate mofetil (MMF) in treating patients with ITP.
METHODS
We systematically searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) from inception until 10 October 2022. We included all clinical trials, either controlled or single arm, and prospective and retrospective observational studies that evaluate the efficacy and safety of MMF in patients with ITP. We assessed the risk of bias using three tools (ROBINS-I, Cochrane ROB-2, and NIH), each for eligible study design.
RESULTS
Nine studies were included in this meta-analysis, with a total of 411 patients with ITP. We found that MMF demonstrated an overall response rate of (62.09%; 95% CI = [43.29 to 77.84]) and the complete response rate was (46.75%; 95% CI = [24.84 to 69.99]). The overall proportion of adverse events was (12%; 95% CI = [6 to 24]). After the sensitivity analysis, the overall response rate became 50%; 95% CI = [38 to 63]) and the complete response rate became (32%; 95% CI = [24 to 42]). However, MMF did not appear to affect white blood cell counts or hemoglobin levels significantly.
CONCLUSION
This systematic review and meta-analysis demonstrate that MMF appears to be an effective and relatively safe treatment option for patients with ITP when combined with steroids and even in those who have not responded to standard therapies (steroid-resistant cases). Further research with well-designed studies is warranted to better understand the factors influencing treatment response and to refine the use of MMF in the management of ITP. An interactive version of our analysis can be accessed from here: https://databoard.shinyapps.io/mycophenolate_meta/.
Topics: Humans; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies; Prospective Studies; Steroids; Immunosuppressive Agents
PubMed: 37981614
DOI: 10.1007/s10067-023-06820-4 -
Pediatrics Jul 2015Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and... (Review)
Review
BACKGROUND
Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and infection. To inform policies around treatment of tuberculosis disease and infection in children, we sought to estimate both the proportion of child tuberculosis cases with isoniazid resistance and the number of incident isoniazid-resistant tuberculosis cases in children, by region.
METHODS
We determined the relationship between rates of isoniazid resistance among child cases and among treatment-naive adult cases through a systematic literature review. We applied this relationship to regional isoniazid resistance estimates to estimate proportions of childhood tuberculosis cases with isoniazid resistance. We applied these proportions to childhood tuberculosis incidence estimates to estimate numbers of children with isoniazid-resistant tuberculosis.
RESULTS
We estimated 12.1% (95% confidence interval [CI] 9.8% to 14.8%) of all children with tuberculosis had isoniazid-resistant disease, representing 120,872 (95% CI 96,628 to 149,059) incident cases of isoniazid-resistant tuberculosis in children in 2010. The majority of these occurred in the Western Pacific and Southeast Asia regions; the European region had the highest proportion of child tuberculosis cases with isoniazid resistance, 26.1% (95% CI: 20.0% to 33.6%).
CONCLUSIONS
The burden of isoniazid-resistant tuberculosis in children is substantial, and risk varies considerably by setting. The large number of child cases signals extensive ongoing transmission from adults with isoniazid-resistant tuberculosis. The risk of isoniazid resistance must be considered when evaluating treatment options for children with disease or latent infection to avoid inadequate treatment and consequent poor outcomes.
Topics: Antitubercular Agents; Global Health; Humans; Incidence; Isoniazid; Tuberculosis, Multidrug-Resistant
PubMed: 26034243
DOI: 10.1542/peds.2015-0172 -
BMJ Clinical Evidence Jun 2010Opportunistic infections can occur in up to 40% of people with HIV infection and a CD4 count less than 250/mm(3), although the risks are much lower with use of highly... (Review)
Review
INTRODUCTION
Opportunistic infections can occur in up to 40% of people with HIV infection and a CD4 count less than 250/mm(3), although the risks are much lower with use of highly active antiretroviral treatment.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylaxis for Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis? What are the effects of antituberculosis prophylaxis in people with HIV infection? What are the effects of prophylaxis for disseminated Mycobacterium avium complex (MAC) disease for people with, and without, previous MAC disease? What are the effects of prophylaxis for cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV)? What are the effects of prophylaxis for invasive fungal disease in people with, and without, previous fungal disease? What are the effects of discontinuing prophylaxis against opportunistic pathogens in people on highly active antiretroviral treatment (HAART)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aciclovir; antituberculosis prophylaxis; atovaquone; azithromycin (alone or plus rifabutin); clarithromycin (alone, or plus rifabutin and ethambutol); discontinuing prophylaxis for CMV, MAC, and PCP; ethambutol added to clarithromycin; famciclovir; fluconazole; isoniazid; itraconazole; oral ganciclovir; rifabutin (alone or plus macrolides); trimethoprim-sulfamethoxazole; and valaciclovir.
Topics: AIDS-Related Opportunistic Infections; Fluconazole; HIV Infections; Humans; Isoniazid; Opportunistic Infections; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 21418688
DOI: No ID Found -
The International Journal of... Apr 2016D-Cycloserine, known from tuberculosis therapy, has been widely introduced to neuropsychiatric studies, since its central active mechanism as a partial NMDA-agonist has... (Review)
Review
D-Cycloserine, known from tuberculosis therapy, has been widely introduced to neuropsychiatric studies, since its central active mechanism as a partial NMDA-agonist has been found. In this review, we evaluate its therapeutic potential in neuropsychological disorders and discuss its pitfalls in terms of dosing and application frequency as well as its safety in low-dose therapy. Therefore, we identified 91 clinical trials by performing a Medline search. We demonstrate in part preliminary but increasing evidence that D-cycloserine may be effective in various psychiatric diseases, including schizophrenia, anxiety disorders, addiction, eating disorders, major depression, and autism as well as in neurological diseases, including dementia, Alzheimer's disease, and spinocerebellar degeneration. D-Cycloserine in low-dose therapy is safe, but there is still a need for new drugs with higher specificity to the different N-methyl-D-aspartate-receptor subunits.
Topics: Animals; Cycloserine; Excitatory Amino Acid Agonists; Humans; Mental Disorders; Nervous System Diseases; Psychotropic Drugs; Receptors, N-Methyl-D-Aspartate
PubMed: 26364274
DOI: 10.1093/ijnp/pyv102 -
Health Technology Assessment... Aug 2016End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival.
OBJECTIVES
To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation.
DATA SOURCES
Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost).
REVIEW METHODS
Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death.
RESULTS
Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC are cost-effective in all considered combinations; MMF was also cost-effective with CSA but not TAC.
LIMITATIONS
The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence.
CONCLUSIONS
TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at £20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42014013544.
FUNDING
The National Institute for Health Research HTA programme.
Topics: Abatacept; Antibodies, Monoclonal; Antilymphocyte Serum; Azathioprine; Basiliximab; Child; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Everolimus; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Models, Economic; Mycophenolic Acid; Recombinant Fusion Proteins; Sirolimus; Tacrolimus; Technology Assessment, Biomedical
PubMed: 27557331
DOI: 10.3310/hta20610 -
Risk Factors for Acquired Rifamycin and Isoniazid Resistance: A Systematic Review and Meta-Analysis.PloS One 2015Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies.
METHODS
Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1) HIV and 2) baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies.
RESULTS
Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I2 58%, 95% CI 26 to 76%). Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11); there was considerable heterogeneity amongst these studies (I2 81%, 95% CI 64 to 90%). Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST) was 0.1% (5th to 95th percentile 0.07 to 3.2%).
CONCLUSION
Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely to contribute to the outcome of ADR. The multifactorial aetiology of ADR in a programmatic setting should be further evaluated via appropriately designed studies.
Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Drug Resistance, Bacterial; Humans; Isoniazid; Rifamycins; Risk; Tuberculosis
PubMed: 26406228
DOI: 10.1371/journal.pone.0139017 -
The Cochrane Database of Systematic... Feb 2014Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system and a leading cause of disability in young and middle-aged adults. Mycophenolate... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system and a leading cause of disability in young and middle-aged adults. Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been used for the prevention of allograft rejection after renal, cardiac, or liver transplant and in patients with autoimmune diseases such as active relapsing-remitting (RRMS) and progressive MS.
OBJECTIVES
To assess the efficacy and safety of MMF for preventing disease activity in patients with RRMS.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (January 14, 2013). We searched three Chinese databases (January 2013) and checked reference lists of identified trials. We contacted authors and pharmaceutical companies to ask for additional information. We applied no language restrictions.
SELECTION CRITERIA
We included randomized controlled trials with a follow-up of at least 12 months that compared MMF as monotherapy or in combination with other treatments versus placebo, another drug, or the same cointervention as the treated group.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the trials for inclusion, assessed trial quality, and extracted data.
MAIN RESULTS
One included study involving 26 participants with new-onset RRMS investigated the efficacy and safety of MMF (13 participants) versus placebo in interferon β-1a-treated participants. It was assessed to be at high risk of bias, and had a small numbers of participants receiving treatment with short-term duration. There was inadequate information provided by the study to determine the effect of MMF in reducing relapses, preventing disability progression, or developing new T2- or new gadolinium (Gd)-enhanced lesions on magnetic resonance imaging (MRI) after a 12-month follow-up period. No data were available at 24 months. No serious adverse effects were reported. All participants in the MMF-treated group suffered from gastrointestinal upset, but none of them discontinued therapy as a result.
AUTHORS' CONCLUSIONS
The evidence we found from one small study was insufficient to determine the effects of MMF as an add-on therapy for interferon β-1a in new-onset RRMS participants.
Topics: Adjuvants, Immunologic; Humans; Immunosuppressive Agents; Interferon beta-1a; Interferon-beta; Multiple Sclerosis, Relapsing-Remitting; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 24505016
DOI: 10.1002/14651858.CD010242.pub2