-
The Cochrane Database of Systematic... Jul 2015Bronchiectasis is a chronic respiratory disease characterised by abnormal dilatation of the bronchi, and presents typically with a chronic productive cough (or chronic... (Review)
Review
BACKGROUND
Bronchiectasis is a chronic respiratory disease characterised by abnormal dilatation of the bronchi, and presents typically with a chronic productive cough (or chronic wet cough in children) and recurrent infective exacerbations. It significantly impacts daily activities and quality of life, and can lead to recurrent hospitalisations, severe lung function impairment, respiratory failure and even death.
OBJECTIVES
To provide an overview of the efficacy and safety of interventions for adults and children with bronchiectasis from Cochrane reviews.To identify gaps in the evidence base that will inform recommendations for new research and reviews, and to summarise information on reported outcomes and make recommendations for the reporting of standard outcomes in future trials and reviews.
METHODS
We included Cochrane reviews of non-cystic fibrosis (CF) bronchiectasis. We searched the Cochrane Database of Systematic Reviews. The search is current to 11 February 2015. We also identified trials that were potentially eligible for, but not currently included in, published reviews to make recommendations for new Cochrane reviews. We assessed the quality of included reviews using the AMSTAR criteria. We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials and guideline data. The primary outcomes were exacerbations, lung function and quality of life.
MAIN RESULTS
We included 21 reviews but extracted data from, and rated the quality of, only nine reviews that reported results for people with bronchiectasis alone. Of the reviews with no usable data, two reviews included studies with mixed clinical populations where data were not reported separately for people with bronchiectasis and 10 reviews did not contain any trials. Of the 40 studies included across the nine reviews, three (number of participants nine to 34) included children. The studies ranged from single session to year-long studies. Each review included from one to 11 trials and 28 (70%) trials in the overview included 40 or fewer participants. The total number of participants included in reviews ranged from 40 to 1040. The age range of adult participants was from 36 to 73 years and children ranged from six to 16 years. The proportion of male participants ranged from 21% to 72%. Where reported, mean baseline forced expiratory volume in one second (FEV1) ranged from 1.17 L to 1.66 L and from 47% to 88% predicted. Most of the reviews had search dates older than two years.We have summarised the published evidence as outlined in Cochrane reviews, but it was not possible to draw definitive conclusions. There was inconclusive evidence on the use of long-term antibiotics and nebulised hypertonic saline for reducing exacerbation frequency and evidence that human deoxyribonuclease (RhDNase) increases exacerbation frequency. Improvements in lung function were reported for inhaled corticosteroids (ICS) though this was small and not clinically relevant. Evidence of benefit for hyperosmolar agents and mucolytics was inconclusive. There was limited evidence of improvements in quality of life with airway clearance techniques and physical therapy but evidence of benefit for hyperosmolar agents was inconclusive. Secondary outcomes were not clearly reported in all trials in the included reviews. Improvements in dyspnoea, wheeze and cough-free days were reported for small trials of ICS and LABA (long-acting beta2-agonsts)/ICS and cough reduction was also reported for a small bromhexine trial. Reduction in sputum production was reported for long-term antibiotics and airway clearance techniques but evidence of benefit for hyperosmolar agents was inconclusive.Adverse events were included as outcomes in seven reviews. The review of long-term (four weeks to one year) prophylactic courses of antibiotics reported significantly more cases of wheeze (Peto odd ratio (OR) 8.56, 95% confidence intervals (CI) 1.63 to 44.93), dyspnoea (12 versus three, P value = 0.01) and chest pain (seven versus zero, P value = 0.01) from the same trial (74 participants) but no differences in occurrence of diarrhoea, rash or number of withdrawals. In the review of mucolytics versus placebo, relevant outcomes were not reported for erdosteine comparisons and no significant adverse effects were reported for bromhexine, though adverse events were associated with RhDNase (OR 28.19, 95% CI 3.77 to 210.85, 1 study). Of the remaining five reviews, adverse events were not reported in the single trials included in the ICS review or the physical therapy review and the impact of adverse events in the single trial included in the inhaled LABA/ICS combination versus ICS review were unclear. The reviews of short-term courses of antibiotics and inhaled hyperosmolar agents reported no significant differences in occurrence of adverse events. Fewer admissions to hospital were reported for long-term antibiotics, but this outcome was not reported in all reviews. No reviews reported differences in mortality, but again this outcome was not included in all reviews.We did not explicitly include antibiotic resistance as an outcome in the review, but this was unclear in the Cochrane reviews and evidence from other trials should be considered.We rated all reviews as high quality (AMSTAR), though opportunities for improved reporting (e.g. summary of findings and GRADE evaluation of the evidence) were identified for inclusion in future updates of the reviews. However, the majority of trials were not high quality and confidence in the effects of treatments, therefore, requires additional evidence from larger and more methodologically robust trials. We evaluated the overall coverage of important topics in bronchiectasis by mapping the quality of the current evidence base against published guidelines and identifying high priority areas for new research on; use of short-course and long-term antibiotics, ICS and oral corticosteroids, inhaled hyperosmolars, mucolytics, and use of airway clearance techniques.
AUTHORS' CONCLUSIONS
This overview clearly points to significant opportunities for further research aimed at improving outcomes for people with bronchiectasis. We have highlighted important endpoints for studies (particularly exacerbations, quality of life and lung function), and areas of clinical practice that are in most urgent need of evidence-based support (including long-term antibiotics, ICSs and mucolytics).As the evidence is confined to small trials of short duration, it is not currently possible to assess the balance between the benefits and potential harms of treatments for bronchiectasis.
Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Bronchiectasis; Child; Deoxyribonucleases; Expectorants; Humans; Nebulizers and Vaporizers; Review Literature as Topic; Saline Solution, Hypertonic
PubMed: 26171905
DOI: 10.1002/14651858.CD010337.pub2 -
The Cochrane Database of Systematic... Nov 2018Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review.
OBJECTIVES
To determine whether the timing of dornase alfa inhalation (in relation to airway clearance techniques or morning versus evening inhalation) has an impact on objective and subjective measures of clinical efficacy in people with cystic fibrosis.
SEARCH METHODS
Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), clinical trial registries and international cystic fibrosis conference proceedings.Date of the most recent search: 06 June 2018.
SELECTION CRITERIA
Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the trial with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation.
DATA COLLECTION AND ANALYSIS
Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed.
MAIN RESULTS
We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence).
AUTHORS' CONCLUSIONS
The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.
Topics: Administration, Inhalation; Adolescent; Child; Combined Modality Therapy; Cystic Fibrosis; Deoxyribonuclease I; Drug Administration Schedule; Humans; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Respiratory Therapy; Time Factors; Young Adult
PubMed: 30480755
DOI: 10.1002/14651858.CD007923.pub5 -
Systematic Reviews Nov 2015Nebulised dornase alfa is used off-label in critically ill patients. We aimed to assess the benefits and harms of nebulised dornase alfa versus placebo, no prophylaxis,... (Comparative Study)
Comparative Study Meta-Analysis Review
Nebulised dornase alfa versus placebo or hypertonic saline in adult critically ill patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.
BACKGROUND
Nebulised dornase alfa is used off-label in critically ill patients. We aimed to assess the benefits and harms of nebulised dornase alfa versus placebo, no prophylaxis, or hypertonic saline on patient-important outcome measures in adult critically ill patients.
METHODS
We performed a systematic review with meta-analysis and trial sequential analysis (TSA) using the Cochrane Collaboration methodology. Eligible trials were randomised clinical trials comparing nebulised dornase alfa with placebo, no prophylaxis, or hypertonic saline. The predefined outcome measures were all-cause mortality, duration of mechanical ventilation, length of stay, and adverse events. Two reviewers independently assessed trials for inclusion, data extraction, and risk of bias. Risk ratios (RRs) with 95 % confidence intervals (CIs) were estimated by conventional cumulative meta-analysis, and the robustness of the primary estimate was assessed by TSA.
RESULTS
Two trials (n = 63) were included; both were judged to have high risk of bias. There was no statistically significant difference in mortality (random effects model RR (95 % CI) 0.73 (0.09-5.77); P = 0.24; I (2) = 30 %). TSA could not be conducted because less than 1 % of the required information size had been accrued. None of the two trials reported adequate and detailed data on any of the secondary outcome measures.
CONCLUSIONS
We found very low quantity and quality of evidence for use of nebulised dornase alfa in adult critically ill patients in this systematic review with meta-analysis.
SYSTEMATIC REVIEW REGISTRATION
The International Prospective Register of Systematic Reviews (PROSPERO), no. CRD442015016047.
Topics: Administration, Inhalation; Critical Illness; Deoxyribonuclease I; Expectorants; Humans; Nebulizers and Vaporizers; Placebos; Randomized Controlled Trials as Topic; Recombinant Proteins; Saline Solution, Hypertonic
PubMed: 26547839
DOI: 10.1186/s13643-015-0142-z -
Journal of Microbiology, Immunology,... Dec 2020Polymorphisms of vitamin D receptors (VDRs), ApaI, BsmI, FokI, and TaqI might affect susceptibility to tuberculosis (TB). In this systematic review and meta-analysis,... (Meta-Analysis)
Meta-Analysis
Vitamin D receptor ApaI (rs7975232), BsmI (rs1544410), Fok1 (rs2228570), and TaqI (rs731236) gene polymorphisms and susceptibility to pulmonary tuberculosis in an Iranian population: A systematic review and meta-analysis.
Polymorphisms of vitamin D receptors (VDRs), ApaI, BsmI, FokI, and TaqI might affect susceptibility to tuberculosis (TB). In this systematic review and meta-analysis, all published articles which investigated the effects of these polymorphisms on the risk of TB in the Iranian population were retrieved. PubMed and Scopus were searched with no date or language restrictions. In this meta-analysis, the Comprehensive Meta-Analysis (CMA) version 2.0 and random effects model were applied. The association of polymorphisms with TB risk was assessed by measuring the odds ratio (ORs) at 95% CI. Heterogeneity was investigated based on Cochran Q-test and I2-index statistics. The significance level was set at 0.05. Also, Egger's regression intercept was determined to measure publication bias. A total of six articles on Iranian populations were included. TaqI (5/6 included studies) showed a significant association with the increased risk of TB based on ORs (allele comparison: 1.57 (1.0, 2.3), p-value: 0.02; additive model of tt/TT: 1.57 (0.9, 2.5), p-value: 0.05; recessive model (tt/Tt + TT): 1.99 (1.2, 3.2), p-value: 0.00; dominant model (tt + Tt/TT): 1.98 (1.1, 3.5), p-value: 0.01). BsmI showed a significant positive effect on TB risk only in its dominant genotype (bb + bB/BB) (1.44 (1.0, 1.9); p-value: 0.02). FokI and ApaI did not show any significant effects on TB development in Iranian populations. Findings showed the significant effect of TaqI polymorphism in all genetic models and the dominant model of BsmI on the increased risk of TB. However, the effects of TaqI and BsmI should be further investigated in a larger sample size.
Topics: Aged; Aged, 80 and over; Deoxyribonucleases, Type II Site-Specific; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Iran; Male; Middle Aged; Mycobacterium tuberculosis; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Tuberculosis, Pulmonary; Vitamin D Deficiency
PubMed: 31740220
DOI: 10.1016/j.jmii.2019.08.011 -
Photodermatology, Photoimmunology &... Nov 2020DNA damage is one of the main factors responsible for photoageing and is predominantly attributed to ultraviolet irradiation (UV-R). Photoprotection by conventional...
BACKGROUND
DNA damage is one of the main factors responsible for photoageing and is predominantly attributed to ultraviolet irradiation (UV-R). Photoprotection by conventional sunscreens is exclusively prophylactic, and of no value, once DNA damage has occurred. As a result, the demand for DNA repair mechanisms inhibiting, reversing or delaying the pathologic events in UV-exposed skin has sparked research on anti-photoageing and strategies to improve the effect of conventional sunscreens. This review provides an overview of recent developments in DNA repair enzymes used in sunscreens and their impact on photoageing.
METHODS
A systematic review of the literature, up to March 2019, was conducted using the electronic databases, PubMed and Web of Science. Quality assessment was carried out using the Newcastle-Ottawa scale (NOS) to ensure inclusion of adequate quality studies only (NOS > 5).
RESULTS
Out of the 352 publications, 52 were considered relevant to the key question and included in the present review. Two major enzymes were found to play a major role in DNA damage repair in sunscreens: photolyase and T4 endonuclease V. These enzymes are capable of identifying and removing UV-R-induced dimeric photoproducts. Clinical studies revealed that sunscreens with liposome-encapsulated types of photolyase and/or T4 endonuclease V can enhance these repair mechanisms.
CONCLUSION
There is a lack of randomized controlled trials demonstrating the efficacy of DNA repair enzymes on photoageing, or a superiority of sunscreens with DNA repair enzymes compared to conventional sunscreens. Further studies are mandatory to further reveal pathogenic factors of photoageing and possible therapeutic strategies against it.
Topics: Animals; DNA Damage; DNA Repair; Deoxyribodipyrimidine Photo-Lyase; Deoxyribonuclease (Pyrimidine Dimer); Humans; Skin Aging; Sunscreening Agents; Ultraviolet Rays; Viral Proteins
PubMed: 32772409
DOI: 10.1111/phpp.12597 -
Scientific Reports Jul 2016An increasing number of studies have highlighted the potential link between EXO1 polymorphisms and cancer risk, although no consensus has yet been obtained. Thus, we... (Meta-Analysis)
Meta-Analysis
An increasing number of studies have highlighted the potential link between EXO1 polymorphisms and cancer risk, although no consensus has yet been obtained. Thus, we aimed to obtain a thorough and current assessment of EXO1 polymorphisms and cancer susceptibility by performing a meta-analysis. A comprehensive literature retrieval was performed on PubMed, EMbase, Web of Science and Wanfang databases. The odds ratio (OR) and 95% confidence interval (CI) were applied to assess the results. Finally, 39 case-control studies of the nine EXO1 polymorphisms that involved 21,651 cases and 21,348 controls met our inclusion criteria. The pooled analysis indicated that the rs1047840 polymorphism conferred a significantly increased susceptibility to cancer in an allelic model. Similarly, the rs3754093, rs1776177, rs9350, rs10802996, rs1635498, rs1776148 and rs851797 polymorphisms were also associated with an increased susceptibility to cancer in an allelic model, respectively, while no significant association was identified for rs1635517 polymorphism. For the rs1047840 polymorphism, in an ethnicity subgroup analysis, a significantly increased susceptibility to cancer for Asians was identified in all the genetic models, and for Caucasians in an allelic model. Our findings provide the evidence that the rs1047840, rs9350, rs10802996, rs1635498, rs1776148, rs1776177, rs3754093 and rs851797 polymorphisms may act as risk factors for cancer.
Topics: Case-Control Studies; DNA Repair Enzymes; Ethnicity; Exodeoxyribonucleases; Genetic Predisposition to Disease; Humans; Neoplasms; Polymorphism, Single Nucleotide
PubMed: 27387683
DOI: 10.1038/srep29270 -
Histopathology Oct 2021There has been an increased demand for mismatch repair (MMR) status testing in sarcoma patients after the success of immune checkpoint inhibition (ICI) in MMR deficient...
INTRODUCTION
There has been an increased demand for mismatch repair (MMR) status testing in sarcoma patients after the success of immune checkpoint inhibition (ICI) in MMR deficient tumors. However, data on MMR deficiency in bone and soft tissue tumors is sparse, rendering it unclear if routine screening should be applied. Hence, we aimed to study the frequency of MMR deficiency in bone and soft tissue tumors after we were prompted by two (potential) Lynch syndrome patients developing sarcomas.
METHODS
Immunohistochemical expression of MLH1, PMS2, MSH2 and MSH6 was assessed on tissue micro arrays (TMAs), and included 353 bone and 539 soft tissue tumors. Molecular data was either retrieved from reports or microsatellite instability (MSI) analysis was performed. In MLH1 negative cases, additional MLH1 promoter hypermethylation analysis followed. Furthermore, a systematic literature review on MMR deficiency in bone and soft tissue tumors was conducted.
RESULTS
Eight MMR deficient tumors were identified (1%), which included four leiomyosarcoma, two rhabdomyosarcoma, one malignant peripheral nerve sheath tumor and one radiation-associated sarcoma. Three patients were suspected for Lynch syndrome. Literature review revealed 30 MMR deficient sarcomas, of which 33% were undifferentiated/unclassifiable sarcomas. 57% of the patients were genetically predisposed.
CONCLUSION
MMR deficiency is rare in bone and soft tissue tumors. Screening focusing on tumors with myogenic differentiation, undifferentiated/unclassifiable sarcomas and in patients with a genetic predisposition / co-occurrence of other malignancies can be helpful in identifying patients potentially eligible for ICI.
Topics: Adult; Biomarkers, Tumor; Bone Neoplasms; Brain Neoplasms; Colorectal Neoplasms; DNA-Binding Proteins; Humans; Male; Middle Aged; Mismatch Repair Endonuclease PMS2; MutL Protein Homolog 1; MutS Homolog 2 Protein; Neoplastic Syndromes, Hereditary; Soft Tissue Neoplasms
PubMed: 33825202
DOI: 10.1111/his.14377 -
Journal of Assisted Reproduction and... May 2014Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different... (Meta-Analysis)
Meta-Analysis
PURPOSE
Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different regions of ESR1 and ESR2 genes. However, results from published studies on the association between four well-characterized polymorphisms (PvuII, XbaI, RsaI, and AluI) in the gene of ERs (ESR1 and ESR2) and male infertility risk are inconclusive.
METHODS
To investigate the strength of relationship of PvuII and XbaI in ESR1 and RsaI and AluI in ESR2 with male infertility, we conducted a meta-analysis of 12 eligible studies with odds ratio (OR) and its corresponding 95 % confidence intervals (95 % CI).
RESULTS
Overall, ESR1 PvuII and ESR2 RsaI polymorphisms were significantly associated with male infertility risk. The subgroup analyses by ethnicities demonstrated that in Asians, ESR1 PvuII, XbaI and ESR2 RsaI polymorphisms were significantly associated with a decreased infertility risk, while in Caucasians both ESR1 PvuII and ESR2 RsaI polymorphisms increased the susceptibility to male infertility. As for ESR2 AluI polymorphism, no significant association was detected in either overall analysis or subgroup analyses by ethnicities/genotyping methods.
CONCLUSIONS
This meta-analysis suggested that polymorphisms in the genes of ERs (ESR1 and ESR2) may have differential roles in the predisposition to male infertility according to the different ethnic backgrounds. Further well-designed and unbiased studies with larger sample size and diverse ethnic backgrounds should be conducted to verify our findings.
Topics: Asian People; Deoxyribonucleases, Type II Site-Specific; Estrogen Receptor alpha; Estrogen Receptor beta; Genetic Predisposition to Disease; Humans; Infertility, Male; Male; Odds Ratio; Polymorphism, Genetic; White People
PubMed: 24647635
DOI: 10.1007/s10815-014-0212-5 -
Modern Pathology : An Official Journal... Dec 2022Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been... (Meta-Analysis)
Meta-Analysis
Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been approved as a pan-cancer predictive biomarker for checkpoint inhibitor therapy, leading to a vast increase in the use of MMR IHC in clinical practice. We explored whether immunohistochemical staining with PMS2 and MSH6 can be used as a reliable substitute. This two-antibody testing algorithm has the benefit of saving tissue, cutting costs and saving time. PubMed, Embase and Cochrane library were systematically searched for articles reporting on MMR IHC. The weighed percentage of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was analyzed using a random effects model meta-analysis in R. The search yielded 1704 unique citations, of which 131 studies were included, describing 9014 patients. A weighed percentage of 1.1% (95% CI 0.53-18.87, I = 87%) of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was observed. In the six articles with the main aim of investigating the two-antibody testing algorithm all MMRd cases were detected with the two-antibody testing algorithm, there were no cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone. This high detection rate of MMRd of the two-antibody testing algorithm supports its use in clinical practice by specialized pathologists. Staining of all four antibodies should remain the standard in cases with equivocal results of the two-antibody testing algorithm. Finally, educational sessions in which staining pattern pitfalls are discussed will continue to be important.
Topics: Humans; Mismatch Repair Endonuclease PMS2; MutL Protein Homolog 1; MutS Homolog 2 Protein; DNA-Binding Proteins; Colorectal Neoplasms; DNA Mismatch Repair; Biomarkers, Tumor; Algorithms
PubMed: 36104536
DOI: 10.1038/s41379-022-01149-w