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The Cochrane Database of Systematic... Oct 2013It is well known that physical exercise can trigger asthma symptoms and can induce bronchial obstruction in people without clinical asthma. International guidelines on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is well known that physical exercise can trigger asthma symptoms and can induce bronchial obstruction in people without clinical asthma. International guidelines on asthma management recommend the use of beta2-agonists at any stage of the disease. At present, however, no consensus has been reached about the efficacy and safety of beta2-agonists in the pretreatment of exercise-induced asthma and exercise-induced bronchoconstriction. For the purpose of the present review, both of these conditions are referred to by the acronymous EIA, independently from the presence of an underlying chronic clinical disease.
OBJECTIVES
To assess the effects of inhaled short- and long-acting beta2-agonists, compared with placebo, in the pretreatment of children and adults with exercise-induced asthma (or exercise-induced bronchoconstriction).
SEARCH METHODS
Trials were identified by electronic searching of the Cochrane Airways Group Specialised Register of Trials and by handsearching of respiratory journals and meetings. Searches are current as of August 2013.
SELECTION CRITERIA
We included randomised, double-blind, placebo-controlled trials of any study design, published in full text, that assessed the effects of inhaled beta2-agonists on EIA in adults and children. We excluded studies that did not clearly state diagnostic criteria for EIA.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by The Cochrane Collaboration.
MAIN RESULTS
We included 53 trials consisting of 1139 participants. Forty-eight studies used a cross-over design, and five were performed in accordance with a parallel-group design. Forty-five studies addressed the effect of a single beta2-agonist administration, and eight focused on long-term treatment. We addressed these two different intervention regimens as different comparisons.Among primary outcomes for short-term administration, data on maximum fall in forced expiratory volume in 1 second (FEV1) showed a significant protective effect for both short-acting beta-agonists (SABA) and long-acting beta-agonists (LABA) compared with placebo, with a mean difference of -17.67% (95% confidence interval (CI) -19.51% to -15.84%, P = 0.00001, 799 participants from 72 studies). The subgroup analysis of studies performed in adults compared with those performed in children showed high heterogeneity confined to children, despite the comparable mean bronchoprotective effect.Secondary outcomes on other pulmonary function parameters confirmed a more positive and protective effect of beta2-agonists on EIA compared with placebo. Occurrence of side effects was not significantly different between beta2-agonists and placebo.Overall evaluation of the included long-term studies suggests a beta2-agonist bronchoprotective effect for the first dose of treatment. However, long-term use of both SABA and LABA induced the onset of tolerance and decreased the duration of drug effect, even after a short treatment period.
AUTHORS' CONCLUSIONS
Evidence of low to moderate quality shows that beta2-agonists, both SABA and LABA, when administered in a single dose, are effective and safe in preventing EIA.Long-term regular administration of inhaled beta2-agonists induces tolerance and lacks sufficient safety data. This finding appears to be of particular clinical relevance in view of the potential for prolonged regular use of beta2-agonists as monotherapy in the pretreatment of EIA, despite the warnings of drug agencies (FDA, EMA) regarding LABA.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Antagonists; Adult; Asthma, Exercise-Induced; Bronchoconstriction; Bronchodilator Agents; Child; Forced Expiratory Volume; Humans; Randomized Controlled Trials as Topic
PubMed: 24089311
DOI: 10.1002/14651858.CD003564.pub3 -
American Journal of Transplantation :... Sep 2020Solid organ transplant (SOT) is frequently complicated by cancers, which render immunosuppression challenging. Immune checkpoint inhibitors have emerged as treatments...
Solid organ transplant (SOT) is frequently complicated by cancers, which render immunosuppression challenging. Immune checkpoint inhibitors have emerged as treatments for many cancers. Data are lacking regarding efficacy and rejection risk in the SOT population. We conducted a systematic literature review and analyzed 83 cases of immune checkpoint inhibitor use for cancer in SOT. Two thirds of these patients received anti-programmed death ligand 1 therapy, 15.7% received anti-cytotoxic T lymphocyte-associated protein 4 therapy, and 10.8% received a combination. Allograft rejection occurred in 39.8% of patients, leading to end-stage organ failure in 71.0% of cases. Outcomes were similar across organs and immunotherapy regimens. The use of immunosuppressants other than steroids, time since transplant, and prior episodes of rejection were associated with the risk of rejection. The median overall survival of patients was 36 weeks. Most of the deaths were related to cancer progression. In nonkidney recipients, graft rejection was strongly associated with worse survival. At the end of the study, 19.3% of the patients were alive, free from rejection and tumor progression. This study highlights the difficult tradeoff facing oncologists and transplant specialists managing transplant recipients with cancer, and the need for prospective data and novel biomarkers for identifying the patients likely to benefit from immunotherapy in the SOT setting.
Topics: Graft Rejection; Humans; Immune Checkpoint Inhibitors; Immunosuppressive Agents; Neoplasms; Organ Transplantation; Prospective Studies
PubMed: 32027461
DOI: 10.1111/ajt.15811 -
The Patient Jan 2022Regulators have called for greater emphasis on the role of the patient voice to inform medical product development and decision making, and expert guidelines and reports...
BACKGROUND
Regulators have called for greater emphasis on the role of the patient voice to inform medical product development and decision making, and expert guidelines and reports for asthma and chronic obstructive pulmonary disease (COPD) both explicitly recommend the consideration of patient preferences in the management of these diseases. Discrete choice experiments (DCEs) are commonly used to quantify stakeholders' treatment preferences and estimate the trade-offs they are willing to make between outcomes such as treatment benefits and risks.
OBJECTIVE
The aim of this systematic literature review is to provide an up-to-date and critical review of DCEs published in asthma and COPD; specifically, we aim to evaluate the subject of preference studies conducted in asthma and COPD, what attributes have been included, stakeholders' preferences, and the consistency in reporting of instrument development, testing and reporting of results.
METHODS
A systematic review of published DCEs on asthma and COPD treatments was conducted using Embase, Medline and the Cochrane Database of Systematic Reviews. Studies were included if they included a DCE conducted in a relevant population (e.g. patients with asthma or COPD or their caregivers, asthma or COPD-treating clinicians, or the general population), and reported quantitative outcomes on participants' preferences. Study characteristics were summarised descriptively, and descriptive analyses of attribute categories, consistency in reporting on key criteria, and stakeholder preferences were undertaken.
RESULTS
A total of 33 eligible studies were identified, including 28 unique DCEs. The majority (n = 20; 71%) of studies were conducted in a patient sample. Studies focused on inhaler treatments, and included attributes in five key categories: symptoms and treatment benefits (n = 23; 82%), treatment convenience (n = 19; 68%), treatment cost (n = 17; 61%), treatment risks (n = 13; 46%), and other (n = 10; 36%). Symptoms and treatment benefits were the attributes most frequently ranked as important to patients (n = 26, 72%), followed by treatment risks (n = 7, 39%). Several studies (n = 9, 32%) did not qualitatively pre-test their DCE, and a majority did not report the uncertainty in estimated outcomes (n = 18; 64%).
CONCLUSIONS
DCEs in asthma and COPD have focused on treatment benefits and convenience, with less evidence generated on participants' risk tolerance. Quality criteria and reporting standards are needed to promote study quality and ensure consistency in reporting between studies.
Topics: Asthma; Choice Behavior; Humans; Patient Preference; Pulmonary Disease, Chronic Obstructive; Systematic Reviews as Topic
PubMed: 34250574
DOI: 10.1007/s40271-021-00536-w -
Helicobacter Sep 2014This review summarizes important studies regarding H.pylori therapy published from April 2013 to April 2014. The main themes that emerge are assessing the efficacy of... (Review)
Review
This review summarizes important studies regarding H.pylori therapy published from April 2013 to April 2014. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, predominantly optimized triple therapies and non-bismuth quadruple schemes. Regarding newer non-bismuth quadruple regimens, the compliance and tolerance seem to be similar for sequential and concomitant regimens. Notably, no study yet has demonstrated a clear statistical superiority for either, and a systematic review and meta-analysis may be warranted. Other studies examined the role of levofloxacin and bismuth based therapies in H. pylori eradication. The efficacy of bismuth as a second-line after sequential therapy was particularly noteworthy. Levofloxacin-based therapies also appear to be useful and versatile as part of different antibiotic combinations and in first-, second-, and third-line therapies. The emerging problem of quinolone resistance remains a worry. Individualized therapy, based on factors such as antimicrobial information, resistance data, and CYP2C19 metabolism, may well be the most notable future trend to emerge this year.
Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans
PubMed: 25167944
DOI: 10.1111/hel.12163 -
Current Urology Reports Feb 2022Urinary tract infections (UTIs) are a common problem, especially in women. Recurrent UTIs (rUTIs) are difficult to treat and while prophylactic antibiotics can be an... (Review)
Review
PURPOSE OF REVIEW
Urinary tract infections (UTIs) are a common problem, especially in women. Recurrent UTIs (rUTIs) are difficult to treat and while prophylactic antibiotics can be an effective strategy, they worsen antimicrobial resistance and incur side effects. We conducted a systematic review of literature to assess the role of probiotics in management of UTIs. All English language articles reporting on randomised trials and cohort studies were selected, while paediatric patients (< 18 years) and patients with neurogenic bladders were excluded.
RECENT FINDINGS
A total of 9 articles (772 patients) met the inclusion criteria with a mean age of 34.2 years (range 18-65 years). A variety of different probiotics were used. Two studies concluded that probiotics could reduce risk of rUTIs; however, the remainder provided inconclusive results. A key advantage demonstrated, however, was the limited side effect profile and tolerance, which allows for good patient compliance with this treatment strategy. There exists only limited clinical evidence to support the role of probiotics in the management of rUTIs, and based on the current evidence, probiotics can be a potential measure to reduce rUTIs, although further randomised studies will help delineate its formal position in the treatment algorithm.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Middle Aged; Probiotics; Urinary Bladder, Neurogenic; Urinary Tract Infections; Young Adult
PubMed: 35156175
DOI: 10.1007/s11934-022-01085-x -
Caspian Journal of Internal Medicine 2016Chronic obstructive pulmonary disease (COPD) is usually considered one of the leading causes of death worldwide, so finding proper therapeutic strategies for this... (Review)
Review
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is usually considered one of the leading causes of death worldwide, so finding proper therapeutic strategies for this disease is of high importance. In this meta-analysis, we reviewed the existing literature on the efficacy and safety of conventional long acting beta agonists (LABAs) in COPD patients.
METHODS
We searched MEDLINE and Google scholar to identify relevant articles. We limited data to double-blinded randomized controlled trials (RCTs). Data of 14, 832 COPD subjects including 7540 patients under a β2 agonist (cases) and 7292 taking placebo (controls) retrieved from 20 randomized controlled trials and were enrolled into this meta-analysis. Evaluated outcomes included overall mortality, exacerbations and tolerance to the drug.
RESULTS
The analysis of survival showed no significant difference between those taking LABAs or placebo (relative risk (RR): 0.945, 95% confidence interval (CI): 0.821-1.088, P=0.432). Exacerbation rate, however, was significantly lower among the cases than among the controls (RR: 0.859, 95%CI: 0.800-0.922, p<0.001). Similar observation was detected in analyzing the rate of drug withdrawal in patients of the two groups with patients under placebo having significantly higher rate of drug discontinuation due to adverse events or disease symptoms (RR:0.821, 95% CI: 0.774-0.871; p<0.007).
CONCLUSION
In conclusion, we found that the use of conventional LABA therapy in COPD patients is associated with a lower exacerbation rate of the disease as well as higher tolerance to the drug, but no survival advantage is expectable. Substitution of LABAs with new agents is recommended.
PubMed: 27386055
DOI: No ID Found -
The Journal of Clinical Endocrinology... Mar 2020The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of... (Meta-Analysis)
Meta-Analysis
CONTEXT
The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear.
OBJECTIVE
The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function.
METHODS
Eight electronic databases were searched for articles published up to May 8, 2018. Fixed or random effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals (CI). This study is reported following the PRISMA and MOOSE guidelines.
DATA SYNTHESIS
52 studies (22 low risk of bias) were included describing 18 428 subjects, consisting of patients with chronic pain (n = 21 studies) or on maintenance treatment for opioid addiction (n = 9) and healthy volunteers (n = 4). The most frequently used opioid was methadone (n = 13 studies), followed by morphine (n = 12). Prevalence of hypogonadism was 63% (95% CI: 55%-70%, 15 studies, 3250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and nondynamic testing was 15% (95% CI: 6%-28%, 5 studies, 205 patients, 57.5% males) and including only studies using the insulin tolerance tests 24% (95% CI 16%-33%, 2 studies, n = 97 patients). In 5 out of 7 studies, hyperprolactinemia was present. No clear effects on the somatotropic and hypothalamo-pituitary-thyroid axes were described.
CONCLUSIONS
Hypogonadism occurs in more than half of male opioid users, and hypocortisolism in approximately one-fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable.
Topics: Analgesics, Opioid; Chronic Pain; Endocrine System Diseases; Humans; Hypogonadism; Pituitary Hormones; Prognosis
PubMed: 31511863
DOI: 10.1210/clinem/dgz022 -
The Journal of Nutrition, Health & Aging 2016The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We... (Review)
Review
BACKGROUND
The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy.
METHOD
We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition.
RESULTS
Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients.
CONCLUSIONS
Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.
Topics: Aged; Antineoplastic Agents; Body Composition; Female; Humans; Male; Middle Aged; Neoplasms
PubMed: 27709238
DOI: 10.1007/s12603-015-0653-2 -
Alimentary Pharmacology & Therapeutics Jun 2024The expanding options in advanced therapies for ulcerative colitis (UC) and Crohn's disease (CD) present challenges in treatment selection. Persistence analysis assesses... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The expanding options in advanced therapies for ulcerative colitis (UC) and Crohn's disease (CD) present challenges in treatment selection. Persistence analysis assesses drug durability in real-world settings, acting as a surrogate marker for medication efficacy and tolerance. Unlike traditional comparative studies, persistence analysis provides insights extending beyond the initial year of treatment.
AIM
To provide real-world evidence on treatment effectiveness, tolerability and preferences of physicians and patients regarding various advanced therapies for IBD.
METHODS
We conducted a systematic review of observational studies up to March 2023 assessing advanced therapies' persistence in UC and CD. Advanced therapies under examination included infliximab, adalimumab, vedolizumab, ustekinumab, golimumab, certolizumab and tofacitinib. We pooled the persistence of each agent and conducted a meta-analysis to compare the persistence of newer agents with traditional TNF inhibitors (TNFi)-specifically infliximab and adalimumab.
RESULTS
Among 63 observational studies, vedolizumab had the highest 1-year persistence in UC (73.8%, 95% CI: 70.0%-77.6%) and ustekinumab in CD (77.5%, 95% CI: 72.9%-82.1%). Compared to TNFi, vedolizumab demonstrated increased persistence with a relative risk (RR) of 1.30 (95% CI: 1.19-1.41) for UC and 1.14 (95% CI: 1.09-1.20) for CD at 1 year, while ustekinumab demonstrated a RR of 1.15 (95% CI: 1.07-1.23) for CD at 1 year. Vedolizumab exhibited sustained increased persistence in UC over 2 years compared to TNFi (RR: 1.33, 95% CI 1.14-1.54).
CONCLUSION
This meta-analysis highlights the superior persistence of ustekinumab and vedolizumab over TNFi, and offers valuable insights for clinicians navigating the challenging landscape of UC and CD therapeutic choices.
Topics: Humans; Gastrointestinal Agents; Ustekinumab; Crohn Disease; Colitis, Ulcerative; Inflammatory Bowel Diseases; Antibodies, Monoclonal, Humanized; Treatment Outcome; Observational Studies as Topic; Infliximab; Piperidines; Antibodies, Monoclonal; Pyrimidines
PubMed: 38651771
DOI: 10.1111/apt.18006 -
Journal of Biomedical Nanotechnology Mar 2016In preceding decades, different mechanisms have been proposed to "instruct" dendritic cells (DCs) to induce immune responses against tumor antigens (TAs), thus breaking... (Review)
Review
In preceding decades, different mechanisms have been proposed to "instruct" dendritic cells (DCs) to induce immune responses against tumor antigens (TAs), thus breaking immune tolerance. Immunotherapy has been, for the last two decades, an attractive and promising therapeutic approach to fight cancer. This review will approach the nature of the immune response during cancer development and its correlation with DC function, as well as cancer vaccine principles and limitations. An overview of several delivery strategies used for in vivo modulation of DCs and direct activation of T cells will be provided, highlighting their advantages, limitations, and optimization strategies. This manuscript also presents a critical and systematic review of recent clinical trials that are investigating the therapeutic effect of these approaches, discussing prognostic outcomes of combined-treatment modalities.
Topics: Animals; Dendritic Cells; Humans; Immunotherapy; Molecular Targeted Therapy; Nanoparticles; Neoplasms; Treatment Outcome
PubMed: 27280242
DOI: 10.1166/jbn.2016.2157