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The Lancet. Infectious Diseases Jan 2018In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings.
METHODS
Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects.
FINDINGS
We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p>0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI -2·71 to -2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001).
INTERPRETATION
Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance.
FUNDING
National Institute for Health Research.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Length of Stay; Male; Middle Aged; Procalcitonin; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Survival Analysis
PubMed: 29037960
DOI: 10.1016/S1473-3099(17)30592-3 -
Jornal de Pediatria 2017The aim of this review was to address advances in management and treatment of acute viral bronchiolitis in infants. (Review)
Review
OBJECTIVE
The aim of this review was to address advances in management and treatment of acute viral bronchiolitis in infants.
SOURCES
A systematic review search was made including all articles published in English between 2010 and 2017, and available in the electronic databases PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) and specialized register of the Acute Respiratory Infections Group (Cochrane review group). The following MESH terms in English were included, using different Boolean operators for the search strategy: "bronchiolitis, viral," "diagnosis," "epidemiology," "etiology," "therapy," "virology," "prevention and control," "respiratory syncytial virus, human." Additional filters were used.
SUMMARY OF FINDINGS
Few effective interventions are recommended for the management of RSV bronchiolitis in young infants. The main goal is to ensure an adequate oxygen supplementation and fluid balance whenever deemed necessary. Hypertonic saline nebulization is helpful only for hospitalized infants. Numerous antiviral drugs and specific vaccines for RSV are under evaluation and foretell advances in disease management in the near future.
CONCLUSION
A number of promising new technologies are advancing in the field. Until new interventions became feasible, early detection and modification of preventable risk factors is essential to improve outcomes.
Topics: Acute Disease; Bronchiolitis, Viral; Humans; Infant, Newborn; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 28859915
DOI: 10.1016/j.jped.2017.07.003 -
The Cochrane Database of Systematic... Aug 2017Bronchiolitis is a common acute respiratory condition with high prevalence worldwide. This clinically diagnosed syndrome is manifested by tachypnoea (rapid breathing),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is a common acute respiratory condition with high prevalence worldwide. This clinically diagnosed syndrome is manifested by tachypnoea (rapid breathing), with crackles or wheeze in young children. In the acute phase of bronchiolitis (≤ 14 days), antibiotics are not routinely prescribed unless the illness is severe or a secondary bacterial infection is suspected. Although bronchiolitis is usually self-limiting, some young children continue to have protracted symptoms (e.g. cough and wheezing) beyond the acute phase and often re-present to secondary care.
OBJECTIVES
To compare the effectiveness of antibiotics versus controls (placebo or no treatment) for reducing or treating persistent respiratory symptoms following acute bronchiolitis within six months of acute illness.
SEARCH METHODS
We searched the following databases: the Cochrane Airways Group Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), the World Health Organization (WHO) trial portal, the Australian and New Zealand Clinical Trials Registry, and ClinicalTrials.gov, up to 26 August 2016.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing antibiotics versus controls (placebo or no treatment) given in the post-acute phase of bronchiolitis (> 14 days) for children younger than two years with a diagnosis of bronchiolitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies against predefined criteria, and selected, extracted, and assessed data for inclusion. We contacted trial authors for further information.
MAIN RESULTS
In this review update, we added one study with 219 children. A total of two RCTs with 249 children (n = 240 completed) were eligible for inclusion in this review. Both studies contributed to our primary and secondary outcomes, but we assessed the quality of evidence for our three primary outcomes as low, owing to the small numbers of studies and participants; and high attrition in one of the studies. Data show no significant differences between treatment groups for our primary outcomes: proportion of children (n = 249) who had persistent symptoms at follow-up (odds ratio (OR) 0.69, 95% confidence interval (CI) 0.37 to 1.28; fixed-effect model); and number of children (n = 240) rehospitalised with respiratory illness within six months (OR 0.54, 95% CI 0.05 to 6.21; random-effects model). We were unable to analyse exacerbation rate because studies used different methods to report this information. Data showed no significant differences between treatment groups for our secondary outcome: proportion of children (n = 240) with wheeze at six months (OR 0.47, 95% CI 0.06 to 3.95; random-effects model). One study reported bacterial resistance, but only at 48 hours (thus with limited applicability for this review). Another study reported adverse events from which all children recovered and remained in the study.
AUTHORS' CONCLUSIONS
Current evidence is insufficient to inform whether antibiotics should be used to treat or prevent persistent respiratory symptoms in the post-acute bronchiolitis phase. Future RCTs are needed to evaluate the efficacy of antibiotics for reducing persistent respiratory symptoms. This is particularly important in populations with high acute and post-acute bronchiolitis morbidity (e.g. indigenous populations in Australia, New Zealand, and the USA).
Topics: Acute Disease; Anti-Bacterial Agents; Bronchiolitis; Clarithromycin; Cough; Humans; Infant; Randomized Controlled Trials as Topic; Respiratory Sounds; Respiratory Syncytial Virus Infections
PubMed: 28828759
DOI: 10.1002/14651858.CD009834.pub3 -
The Cochrane Database of Systematic... Jun 2017Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. Chronic obstructive pulmonary disease is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis.
OBJECTIVES
To assess the effectiveness of an oral, whole-cell NTHi vaccine in protecting against recurrent episodes of acute exacerbations of chronic bronchitis and COPD in adults. To assess the effectiveness of NTHi vaccine in reducing NTHi colonising the respiratory tract during recurrent episodes of acute exacerbations of COPD.
SEARCH METHODS
We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), CINAHL (1981 to January 2017), LILACS (1985 to January 2017), and Web of Science (1955 to January 2017). We also searched trials registries and contacted authors of trials requesting unpublished data.
SELECTION CRITERIA
We included randomised controlled trials comparing the effects of an oral monobacterial NTHi vaccine in adults with recurrent acute exacerbations of chronic bronchitis or COPD when there was overt matching of the vaccine and placebo groups on clinical grounds. The selection criteria considered populations aged less than 65 years and those older than 65 years.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data from original records and publications for incidence and severity of bronchitis episodes and carriage rate of NTHi measured in the upper respiratory tract, as well as data relevant to other primary and secondary outcomes.
MAIN RESULTS
We identified six placebo-controlled randomised controlled trials with a total of 557 participants. These trials investigated the efficacy of enteric-coated, killed preparations of H influenzae in populations prone to recurrent acute exacerbations of chronic bronchitis or COPD. The vaccine preparation and immunisation regimen in all trials consisted of at least three courses of formalin-killed H influenzae in enteric-coated tablets taken at intervals (e.g. days 0, 28, and 56). Each course generally consisted of two tablets taken after breakfast over three consecutive days. In all cases the placebo groups took enteric-coated tablets containing glucose. Risk of bias was moderate across the studies, namely due to the lack of information provided about methods and inadequate presentation of results.Meta-analysis of the oral NTHi vaccine showed a small, non-statistically significant reduction in the incidence of acute exacerbations of chronic bronchitis or COPD (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.57 to 1.10; P = 0.16). There was no significant difference in mortality rate between the vaccine and placebo groups (odds ratio (OR) 1.62, 95% CI 0.63 to 4.12; P = 0.31).We were unable to meta-analyse the carriage levels of NTHi in participants as each trial reported this result using different units and tools of measurement. Four trials showed no significant difference in carriage levels, while two trials showed a significant decrease in carriage levels in the vaccinated group compared with the placebo group.Four trials assessed severity of exacerbations measured by requirement for antibiotics. Three of these trials were comparable and when meta-analysed showed a statistically significant 80% increase in antibiotic courses per person in the placebo group (RR 1.81, 95% CI 1.35 to 2.44; P < 0.001). There was no significant difference between the groups with regard to hospital admission rates (OR 0.96, 95% CI 0.13 to 7.04; P = 0.97). Adverse events were reported in five trials but were not necessarily related to the vaccine; a point estimate is suggestive that they occurred more frequently in the vaccine group, however this result was not statistically significant (RR 1.43, 95% CI 0.70 to 2.92; P = 0.87). Quality of life was not meta-analysed but was reported in two trials, with results at six months showing an improvement in quality of life in the vaccinated group (scoring at least two points better than placebo).
AUTHORS' CONCLUSIONS
Analyses demonstrate that NTHi oral vaccination of people with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations. Evidence was mixed, and the individual trials that showed a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchitis, Chronic; Disease Progression; Haemophilus Vaccines; Haemophilus influenzae; Humans; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Secondary Prevention; Tablets, Enteric-Coated
PubMed: 28626902
DOI: 10.1002/14651858.CD010010.pub3 -
The Cochrane Database of Systematic... Jun 2017The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care.
OBJECTIVES
To assess the effects of antibiotics in improving outcomes and to assess adverse effects of antibiotic therapy for people with a clinical diagnosis of acute bronchitis.
SEARCH METHODS
We searched CENTRAL 2016, Issue 11 (accessed 13 January 2017), MEDLINE (1966 to January week 1, 2017), Embase (1974 to 13 January 2017), and LILACS (1982 to 13 January 2017). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 5 April 2017.
SELECTION CRITERIA
Randomised controlled trials comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in people without underlying pulmonary disease.
DATA COLLECTION AND ANALYSIS
At least two review authors extracted data and assessed trial quality.
MAIN RESULTS
We did not identify any new trials for inclusion in this 2017 update. We included 17 trials with 5099 participants in the primary analysis. The quality of trials was generally good. At follow-up there was no difference in participants described as being clinically improved between the antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15). Participants given antibiotics were less likely to have a cough (4 studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 6) and a night cough (4 studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7). Participants given antibiotics had a shorter mean cough duration (7 studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated participants were more likely to be improved according to clinician's global assessment (6 studies with 891 participants, RR 0.61, 95% CI 0.48 to 0.79; NNTB 11) and were less likely to have an abnormal lung exam (5 studies with 613 participants, RR 0.54, 95% CI 0.41 to 0.70; NNTB 6). Antibiotic-treated participants also had a reduction in days feeling ill (5 studies with 809 participants, MD -0.64 days, 95% CI -1.16 to -0.13) and days with impaired activity (6 studies with 767 participants, MD -0.49 days, 95% CI -0.94 to -0.04). The differences in proportions with activity limitations at follow-up did not reach statistical significance. There was a significant trend towards an increase in adverse effects in the antibiotic group (12 studies with 3496 participants, RR 1.20, 95% CI 1.05 to 1.36; NNT for an additional harmful outcome 24).
AUTHORS' CONCLUSIONS
There is limited evidence of clinical benefit to support the use of antibiotics in acute bronchitis. Antibiotics may have a modest beneficial effect in some patients such as frail, elderly people with multimorbidity who may not have been included in trials to date. However, the magnitude of this benefit needs to be considered in the broader context of potential side effects, medicalisation for a self limiting condition, increased resistance to respiratory pathogens, and cost of antibiotic treatment.
Topics: Acute Disease; Anti-Bacterial Agents; Bronchitis; Cough; Humans; Randomized Controlled Trials as Topic
PubMed: 28626858
DOI: 10.1002/14651858.CD000245.pub4 -
Annals of Family Medicine Nov 2016Community-acquired pneumonia (CAP), acute cough, bronchitis, and lower respiratory tract infections (LRTI) are often caused by infections with viruses or . The... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Community-acquired pneumonia (CAP), acute cough, bronchitis, and lower respiratory tract infections (LRTI) are often caused by infections with viruses or . The prevalence of atypical pathogens , , , and among patients with these illnesses in the ambulatory setting has not been previously summarized. We set out to derive prevalence information from the existing literature.
METHODS
We performed a systematic review of MEDLINE for prospective, consecutive-series studies reporting the prevalence of and/or in outpatients with cough, acute bronchitis, LRTI, or CAP. Articles were independently reviewed by 2 authors for inclusion and abstraction of data; discrepancies were resolved by consensus discussion. A meta-analysis was performed on each pathogen to calculate the pooled prevalence estimates using a random effects model of raw proportions.
RESULTS
Fifty studies met our inclusion criteria. While calculated heterogeneity was high, most studies reported prevalence for each pathogen within a fairly narrow range. In patients with CAP, the overall prevalences of and were 10.1% (95% CI, 7.1%-13.1%) and 3.5% (95% CI, 2.2%-4.9%), respectively. Consistent with previous reports, prevalence peaked in roughly 6-year intervals. Overall prevalence of was 2.7% (95% CI, 2.0%-3.4%), but the organism was rare in children, with only 1 case in 1,765. In patients with prolonged cough in primary care, the prevalence of was 12.4% (95% CI, 4.9%-19.8%), although it was higher in studies that included only children (17.6%; 95% CI, 3.4%-31.8%).
CONCLUSIONS
Atypical bacterial pathogens are relatively common causes of lower respiratory diseases, including cough, bronchitis, and CAP. Where surveillance data were available, we found higher prevalences in studies where all patients are tested for these pathogens. It is likely that these conditions are underreported, underdiagnosed, and undertreated in current clinical practice.
Topics: Bordetella pertussis; Chlamydophila pneumoniae; Community-Acquired Infections; Cough; Humans; Legionella pneumophila; Mycoplasma pneumoniae; Pneumonia, Bacterial; Prevalence
PubMed: 28376442
DOI: 10.1370/afm.1993 -
Minerva Anestesiologica Jun 2017Non-invasive ventilation (NIV) is a common treatment for bronchiolitis. However, consensus concerning its efficacy is lacking. The aim of this systematic review was to...
INTRODUCTION
Non-invasive ventilation (NIV) is a common treatment for bronchiolitis. However, consensus concerning its efficacy is lacking. The aim of this systematic review was to assess NIV effectiveness to reduce respiratory distress. Secondary objectives were to summarize the effects of NIV, identify predictive factors for failure and describe settings and applications.
EVIDENCE ACQUISITION
Literature searches were conducted in MEDLINE/PubMed, PEDro, Cochrane, EMBASE, CINAHL, Web of Science, UpToDate, and SuDoc from 1990 to April 2015. Randomized controlled trials, controlled non-randomized trials and prospective studies of NIV (continuous positive airway pressure [CPAP], bi-level CPAP, or neurally-adjusted ventilator assist) for bronchiolitis in infants younger than 2 years were included.
EVIDENCE SYNTHESIS
Fourteen studies were included, for a total of 379 children. Of these, 357 were treated with NIV as first intention. Respiratory distress, heart rate, respiratory rate and respiratory effort improved (P<0.05). Results were inconclusive regarding prevention of endotracheal intubation. Few adverse events were reported. NIV reduced carbon dioxide pressure (pCO2) in 10 studies. Two randomized controlled studies reported a decrease of 7 mmHg in pCO2 (P<0.05). Predictive factors of NIV failure were apneas, high pCO2, young age, low weight, elevated heart rate and high pediatric risk of mortality score. NIV is mostly administered through a nasal mask, nasal cannula or helmet, with an initial expiratory positive airway pressure of 7 cmH2O.
CONCLUSIONS
NIV shows promising results for the reduction of respiratory distress in acute viral bronchiolitis, as shown in several recent studies. However, there is a lack of robust studies to confirm this.
Topics: Acute Disease; Bronchiolitis, Viral; Child; Continuous Positive Airway Pressure; Humans; Noninvasive Ventilation; Respiration Disorders
PubMed: 28192893
DOI: 10.23736/S0375-9393.17.11708-6 -
Antimicrobial Agents and Chemotherapy Jul 2016Antibiotic use is a modifiable driver of antibiotic resistance. In many circumstances, antibiotic use is overly broad or unnecessary. We systematically assessed factors... (Review)
Review
Antibiotic use is a modifiable driver of antibiotic resistance. In many circumstances, antibiotic use is overly broad or unnecessary. We systematically assessed factors associated with antibiotic prescribing for respiratory tract infections (RTI). Studies were included if they used actual (not self-reported or intended) prescribing data, assessed factors associated with antibiotic prescribing for RTIs, and performed multivariable analysis of associations. We searched Medline, Embase, and International Pharmaceutical Abstracts using keyword and MeSH (medical subject headings) search terms. Two authors reviewed each abstract and independently appraised all included texts. Data on factors affecting antibiotic prescribing were extracted. Our searches retrieved a total of 2,848 abstracts, with 97 included in full-text review and 28 meeting full inclusion criteria. Compared to other factors, diagnosis of acute bronchitis was associated with increased antibiotic prescribing (range of adjusted odds ratios [aOR], 1.56 to 15.9). Features on physical exam, such as fever, purulent sputum, abnormal respiratory exam, and tonsillar exudate, were also associated with higher odds of antibiotic prescribing. Patient desire for an antibiotic was not associated or was modestly associated with prescription (range of aORs, 0.61 to 9.87), in contrast to physician perception of patient desire for antibiotics, which showed a stronger association (range of aORs, 2.11 to 23.3). Physician's perception of patient desire for antibiotics was strongly associated with antibiotic prescribing. Antimicrobial stewardship programs should continue to expand in the outpatient setting and should emphasize clear and direct communication between patients and physicians, as well as signs and symptoms that do and do not predict bacterial etiology of upper respiratory tract infections.
Topics: Animals; Anti-Bacterial Agents; Bronchitis; Drug Prescriptions; Humans; Respiratory Tract Infections
PubMed: 27139474
DOI: 10.1128/AAC.00209-16 -
Complementary Therapies in Medicine Apr 2016Acute bronchitis (AB) is one of the common diseases. Tanreqing injection (TRQ) was widely used to treat patients with acute bronchitis, and many randomized controlled... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute bronchitis (AB) is one of the common diseases. Tanreqing injection (TRQ) was widely used to treat patients with acute bronchitis, and many randomized controlled trials have been conducted to investigate its efficacy.
OBJECTIVE
The purpose of this systematic review is to evaluate the efficacy and safety of TRQ for AB.
METHODS
Eight English and Chinese electronic databases, up to October 2014, were searched to identify randomized controlled trials on TRQ for AB. Two reviewers independently extracted data and assessed the quality of each trial by using Cochrane handbook. Meta-analysis was carried out by using Review Manager software.
RESULT
A total of 49 trials with 5131 participants were collected. Data of three main outcomes were pooled and analyzed as following: (1) effective rates: TRQ versus antibiotics (RR 1.12; 95% CI 1.05, 1.18; P=0.0002); TRQ plus antiviral drugs versus antiviral drugs (RR: 5.12; 95% CI 3.03, 8.66; P<0.00001); TRQ plus antibiotics versus antibiotics (RR 3.46; 95% CI 2.59, 4.62; P<0.00001); TRQ versus antibiotics plus antiviral drugs (RR 2.03; 95% CI 1.10, 3.74; P=0.02); TRQ plus conventional therapy versus conventional therapy alone (RR 1.21; 95% CI 1.15, 1.27; P<0.00001). (2) Time for fever resolution: TRQ plus antiviral drugs versus antiviral drugs (MD: -1.08; 95% CI -1.59, -0.57; P<0.00001); TRQ plus antibiotics versus antibiotics (MD -1.33; 95% CI -1.81, -0.86; P<0.00001); TRQ versus antibiotics plus antiviral drugs (MD -0.88; 95% CI -1.25, -0.51; P<0.00001); TRQ plus conventional therapy versus conventional therapy alone (MD -1.06; 95% CI -1.13, -0.98; P<0.00001). (3) Resolution of cough: TRQ plus antiviral drugs versus antiviral drugs (MD: -2.09; 95% CI -3.11, -1.43; P<0.00001); TRQ plus antibiotics versus antibiotics (MD: -2.65; 95% CI -2.88, -2.42; P<0.00001); TRQ plus conventional therapy versus conventional therapy alone (MD -1.84; 95% CI -2.85, -0.83; P=0.0003). Four trials described the adverse drug reactions of TRQ, while no severe adverse drug reactions reported.
CONCLUSIONS
As a therapy for AB, TRQ has potentially beneficial effect in improving effective rates, reducing the time to resolution of fever, cough, crackles and absorption of shadows on X-ray. However, due to the limitations of methodological quality of the included trials, it is difficult to make a conclusive recommendation about TRQ treating patients with AB. Further rigorous clinical trials are warranted to evaluate the efficacy and safety of TRQ.
Topics: Acute Disease; Anti-Bacterial Agents; Bronchitis; Drugs, Chinese Herbal; Humans; Randomized Controlled Trials as Topic
PubMed: 27062962
DOI: 10.1016/j.ctim.2016.02.008 -
Anti-cancer Drugs Jul 2016Treatment of acute myeloid leukaemia (AML) is challenging and emerging treatment options include protein phosphatase 2A (PP2A) activators. Fingolimod is a known PP2A... (Meta-Analysis)
Meta-Analysis
Treatment of acute myeloid leukaemia (AML) is challenging and emerging treatment options include protein phosphatase 2A (PP2A) activators. Fingolimod is a known PP2A activator that inhibits multiple signalling pathways and has been used extensively in patients with multiple sclerosis and other indications. The initial positive results of PP2A activators in vitro and mouse models of AML are promising; however, its safety for use in AML has not been assessed. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A literature review was carried out to assess safety before the commencement of Phase I trials of the PP2A activator Fingolimod in AML. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A systematic review of published literature in Medline, EMBASE and the Cochrane Library of critical reviews was carried out. International standards for the design and reporting of search strategies were followed. Search terms and medical subject headings used in trials involving PP2A activators as well as a specific search were performed for 'adverse events', 'serious adverse events', 'delays in treatment', ' side effects' and 'toxicity' for primary objectives. Database searches were limited to papers published in the last 12 years and available in English. The search yielded 677 articles. A total of 69 journal articles were identified as relevant and included 30 clinical trials, 24 review articles and 15 case reports. The most frequently reported adverse events were nausea, diarrhoea, fatigue, back pain, influenza viral infections, nasopharyngitis and bronchitis. Specific safety concerns include monitoring of the heart rate and conduction at commencement of treatment as cardiotoxicity has been reported. There is little evidence to suggest specific bone marrow toxicity. Lymophopenia is a desired effect in the management of multiple sclerosis, but may have implications in patients with acute leukaemia as it may potentially increase susceptibility to viral infections such as influenza. Fingolimod is a potential treatment option for AML with an acceptable risk to benefit ratio, given its lack of bone marrow toxicity and the relatively low rate of serious side effects. As most patients with AML are elderly, specific monitoring for cardiac toxicity as well as infection would be required.
Topics: Antineoplastic Agents; Cardiovascular Diseases; Fingolimod Hydrochloride; Humans; Infections; Leukemia, Myeloid, Acute; Observational Studies as Topic
PubMed: 26967515
DOI: 10.1097/CAD.0000000000000358