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Heliyon Feb 2024Cancers are one of the most public health problems worldwide. Among them, cervical cancer (CC) is the fourth most prevalent cancer with 604 000 new cases and 342 000... (Review)
Review
Cancers are one of the most public health problems worldwide. Among them, cervical cancer (CC) is the fourth most prevalent cancer with 604 000 new cases and 342 000 deaths. Mostly, it is associated with Human papillomavirus (HPV). It has been caused by the aggregation of genetic and epigenetic modifications in cervical epithelial cells. Although genetic mutations are given great attention for the carcinogenesis of CC, epigenetic changes have emerged as a hotspot area for CC biomarkers research with great implications for early diagnosis, prognosis, and treatment response prediction of the disease. Recently, there are several studies focused on miRNAs as biomarkers of cervical cancer. However, the precise function of miRNAs in the development of cervical cancer is not still completely understood, particularly when it comes to unconventional sampling materials like cervical mucus and plasma serum. Hence, this review article will give a summary of the miRNAs profiles that emerge at different stages of cervical cancer progression and their downstream effects on target genes and associated signaling pathways. Finally, these results may provide insight into the use of miRNAs as biomarkers for the prediction or diagnosis of cervical cancer or the development of miRNA-based therapeutics against cervical cancer.
PubMed: 38317930
DOI: 10.1016/j.heliyon.2024.e24398 -
The Cochrane Database of Systematic... Apr 2016This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Systemic and topical antibiotics are used with the aim of eliminating infection in the short term (and some to reduce inflammation in the long term), in order to normalise nasal mucus and improve symptoms.
OBJECTIVES
To assess the effects of systemic and topical antibiotics in people with chronic rhinosinusitis.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL (2015, Issue 8); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 29 September 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing systemic or topical antibiotic treatment to (a) placebo or (b) no treatment or (c) other pharmacological interventions.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - gastrointestinal disturbance. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of suspected allergic reaction (rash or skin irritation) and anaphylaxis or other very serious reactions. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included five RCTs (293 participants), all of which compared systemic antibiotics with placebo or another pharmacological intervention.The varying study characteristics made comparison difficult. Four studies recruited only adults and one only children. Three used macrolide, one tetracycline and one a cephalosporin-type antibiotic. Three recruited only patients with chronic rhinosinusitis without nasal polyps, one recruited patients with chronic rhinosinusitis with nasal polyps and one had a mixed population. Three followed up patients for 10 to 12 weeks after treatment had finished. Systemic antibiotics versus placebo Three studies compared antibiotics with placebo (176 participants).One study (64 participants, without polyps) reported disease-specific HRQL using the SNOT-20 (0 to 5, 0 = best quality of life). At the end of treatment (three months) the SNOT-20 score was lower in the group receiving macrolide antibiotics than the placebo group (mean difference (MD) -0.54 points, 95% confidence interval (CI) -0.98 to -0.10), corresponding to a moderate effect size favouring antibiotics (moderate quality evidence). Three months after treatment, it is uncertain if there was a difference between groups.One study (33 participants, with polyps) provided information on gastrointestinal disturbances and suspected allergic reaction (rash or skin irritation) after a short course of tetracycline antibiotic compared with placebo. We are very uncertain if antibiotics were associated with an increase in gastrointestinal disturbances (risk ratio (RR) 1.36, 95% CI 0.22 to 8.50) or skin irritation (RR 6.67, 95% CI 0.34 to 128.86) (very low quality evidence). Systemic antibiotics plus saline irrigation and intranasal corticosteroids versus placebo plus saline irrigation and intranasal corticosteroids One study (60 participants, some with and some without polyps) compared a three-month course of macrolide antibiotic with placebo; all participants also used saline irrigation and 70% used intranasal corticosteroids. Disease-specific HRQL was reported using SNOT-22 (0 to 110, 0 = best quality of life). Data were difficult to interpret (highly skewed and baseline imbalances) and it is unclear if there was an important difference at any time point (low quality evidence). To assess patient-reported disease severity participants rated the effect of treatment on a five-point scale (-2 for "desperately worse" to 2 for "cured") at the end of treatment (three months). For improvement in symptoms there was no difference between the antibiotics and placebo groups; the RR was 1.50 (95% CI 0.81 to 2.79; very low quality evidence), although there were also slightly more people who felt worse after treatment in the antibiotics group. There was no demonstrable difference in the rate of gastrointestinal disturbances between the groups (RR 1.07, 95% CI 0.16 to 7.10). General HRQL was measured using the SF-36. The authors stated that there was no difference between groups at the end of treatment (12 weeks) or two weeks later. Systemic antibiotics versus intranasal corticosteroids One study (43 participants, without polyps) compared a three-month course of macrolide antibiotic with intranasal corticosteroids. Patient-reported disease severity was assessed using a composite symptom score (0 to 40; 0 = no symptoms). It is very uncertain if there was a difference as patient-reported disease severity was similar between groups (MD -0.32, 95% CI -2.11 to 1.47; low quality evidence). Systemic antibiotics versus oral corticosteroids One study (28 participants, with polyps) compared a short course of tetracycline antibiotic (unclear duration, ˜20 days) with a 20-day course of oral corticosteroids. We were unable to extract data on any of the primary efficacy outcomes. It is uncertain if there was a difference ingastrointestinal disturbances (RR 1.00, 95% CI 0.16 to 6.14) or skin irritation (RR 2.00, 95% CI 0.20 to 19.62) as the results for these outcomes were similar between groups (very low quality evidence).
AUTHORS' CONCLUSIONS
We found very little evidence that systemic antibiotics are effective in patients with chronic rhinosinusitis. We did find moderate quality evidence of a modest improvement in disease-specific quality of life in adults with chronic rhinosinusitis without polyps receiving three months of a macrolide antibiotic. The size of improvement was moderate (0.5 points on a five-point scale) and only seen at the end of the three-month treatment; by three months later no difference was found.Despite a general understanding that antibiotics can be associated with adverse effects, including gastrointestinal disturbances, the results in this review were very uncertain because the studies were small and few events were reported.No RCTs of topical antibiotics met the inclusion criteria.More research in this area, particularly evaluating longer-term outcomes and adverse effects, is required.
Topics: Administration, Intranasal; Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Child; Chronic Disease; Drug Hypersensitivity; Humans; Nasal Polyps; Nasal Sprays; Quality of Life; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis; Time Factors
PubMed: 27113482
DOI: 10.1002/14651858.CD011994.pub2 -
Respiratory Care Jul 2015Pharmacologic agents to promote mucus clearance may reduce the sequelae of obstructive secretions. We systematically reviewed comparative studies of pharmacologic agents... (Review)
Review
Pharmacologic agents to promote mucus clearance may reduce the sequelae of obstructive secretions. We systematically reviewed comparative studies of pharmacologic agents for mucus clearance in hospitalized or postoperative subjects without cystic fibrosis and over 12 months of age. We searched MEDLINE and other databases from January 1970 to July 2014 to identify relevant literature. Two reviewers independently assessed each study against predetermined inclusion/exclusion criteria. Two reviewers also independently extracted data regarding subject and intervention characteristics and outcomes and assigned overall quality ratings. The 9 studies meeting review criteria included 5 randomized controlled trials, 3 crossover randomized controlled trials, and one retrospective cohort study. Studies were small and together included a total of 379 subjects (mean of 42 subjects per study). N-acetylcysteine, heparin plus N-acetylcysteine, albuterol, ipratropium bromide, and saline were assessed. Studies reported no benefit of studied agents on expectoration, pulmonary function, and atelectasis and little effect on changes in sputum volume, weight, or viscosity. Adverse effects of agents were not consistently reported. Nausea was reported in 2 studies of N-acetylcysteine (one paper reported 2 experiments and did not clearly identify in which experiment adverse effects occurred), 3 studies reported that there were no adverse events, and 3 studies did not address adverse effects at all. Further research with clearly characterized populations and interventions is needed to understand the potential benefits and adverse effects of mucoactive agents.
Topics: Airway Management; Expectorants; Hospitalization; Humans; Mucociliary Clearance; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 25944943
DOI: 10.4187/respcare.04086 -
The Cochrane Database of Systematic... Dec 2021Cystic fibrosis (CF) is the most common, life-limiting, genetically inherited disease. It affects multiple organs, particularly the respiratory system. However,... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is the most common, life-limiting, genetically inherited disease. It affects multiple organs, particularly the respiratory system. However, gastrointestinal problems such as constipation and distal intestinal obstruction syndrome (DIOS) are also important and well-recognised complications in CF. They share similar symptoms e.g. bloating, abdominal pain, but are distinct conditions. Constipation occurs when there is gradual faecal impaction of the colon, but DIOS occurs when there is an accumulation of faeces and sticky mucus, forming a mass in the distal part of the small intestine. The mass may partially block the intestine (incomplete DIOS) or completely block the intestine (complete DIOS). Symptoms of DIOS can affect quality of life and other aspects of CF health, such as airway clearance, exercise, sleep and nutritional status. Treatment of constipation and prevention of complete bowel obstruction are required for gastrointestinal management in CF. However, many different strategies are used in clinical practice and there is a lack of consensus. The importance of this topic was highlighted in a recent research priority setting exercise by the James Lind Alliance.
OBJECTIVES
To evaluate the effectiveness and safety of laxative agents of differing types for preventing DIOS (complete and incomplete) in children and adults with CF.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of search: 09 September 2021. We also searched online trial registries. Date of last search: 12 October 2021.
SELECTION CRITERIA
Randomised and quasi-randomised controlled parallel trials comparing laxative therapy for preventing DIOS (including osmotic agents, stimulants, mucolytics and substances with more than one action) at any dose to placebo, no treatment or an alternative laxative therapy, in people of any age with pancreatic sufficient or insufficient CF and any stage of lung disease. Randomised cross-over trials were judged on an individual basis.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for inclusion, extracted outcome data and performed a risk of bias assessment for the included data. We judged the certainty of the evidence using GRADE criteria.
MAIN RESULTS
We included one cross-over trial (17 participants) with a duration of 12 months, in which participants were randomly allocated to either cisapride (a gastro-prokinetic agent) or placebo for six months each. The trial had an unclear risk of bias for most domains but had a high risk of reporting bias. Radiograph scores revealed no difference in occurrence of DIOS between cisapride and placebo (narrative report, no data provided). There were no adverse effects. Symptom scores were the only secondary outcome within the review that were reported. Total gastrointestinal symptom scores favoured cisapride with a statistically significant mean difference (MD) of -7.60 (95% confidence interval (CI) -14.73 to -0.47). There was no significant difference at six months between cisapride and placebo for abdominal distension, MD -0.90 (95% CI -2.39 to 0.59) or abdominal pain, MD -0.4 (95% CI -2.05 to 1.25). The global symptom scores (whether individuals felt better or worse) were reported in the paper to favour cisapride and be statistically significant (P < 0.05). We assessed the available data to be very low certainty. There was a great deal of missing data from the included trial and the investigators failed to report numerical data for many outcomes. The overall risk of bias of the trial was unclear and it had a high risk for reporting bias. There was also indirectness; the trial drug (cisapride) has since been removed from the market in several countries due to adverse effects, thus it has no current applicability for preventing DIOS. The included trial also had very few participants, which downgraded the certainty a further level for precision.
AUTHORS' CONCLUSIONS
There is an absence of evidence for interventions for the prevention of DIOS. As there was only one included trial, we could not perform a meta-analysis of the data. Furthermore, the included trial compared a prokinetic agent (cisapride) that is no longer licensed for use in a number of countries due to the risk of serious cardiac events, a finding that came to light after the trial was conducted. Therefore, the limited findings from the trial are not applicable in current clinical practice. Overall, a great deal more research needs to be undertaken on gastrointestinal complications in CF, as this is a very poorly studied area compared to respiratory complications in CF.
Topics: Cisapride; Constipation; Cystic Fibrosis; Humans; Intestinal Obstruction; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 34936085
DOI: 10.1002/14651858.CD012619.pub3 -
Sleep Medicine Reviews Jun 2020Cystic fibrosis (CF) is a genetic disorder that leads to airway mucus accumulation, chronic inflammation, and recurrent respiratory infections - all likely impacting... (Meta-Analysis)
Meta-Analysis
Cystic fibrosis (CF) is a genetic disorder that leads to airway mucus accumulation, chronic inflammation, and recurrent respiratory infections - all likely impacting sleep. However, controlled studies of sleep in CF patients are limited, and have shown mixed results. We reviewed all publications on CF and sleep indexed in PubMed, CINAHL, and Scopus through April 2019. In the meta-analysis, we calculated pooled weighted mean differences for sleep quality, sleepiness, oximetry, and polysomnographic (PSG) parameters, using fixed or random-effects models as appropriate. A total of 87 manuscripts were reviewed. Compared to controls, children with CF had lower nighttime oxygen saturation nadirs, decreased sleep efficiency and a higher respiratory event index, with no differences in the percentage of REM sleep. Adults with CF had lower oxygen saturation nadirs, with a trend towards reduced sleep efficiency and no differences in REM sleep. In addition, patients with CF cough more during sleep and experience painful events that interfere with sleep. Actigraphy and questionnaires suggest disturbed sleep and daytime sleepiness. Noninvasive ventilation appears to improve gas exchange and symptoms. We conclude that when sleep is evaluated objectively or subjectively in patients with CF, perturbations are common, emphasizing the importance of their identification and treatment and inclusion as part of routine care. Additional research, with larger sample sizes and standardized outcomes, are necessary.
Topics: Actigraphy; Cystic Fibrosis; Disorders of Excessive Somnolence; Humans; Oximetry; Polysomnography; Severity of Illness Index; Sleep Wake Disorders
PubMed: 32145647
DOI: 10.1016/j.smrv.2020.101279 -
Nutrients Oct 2019In physiological conditions, the gut is heavily infiltrated with various subsets of inflammatory cells, whose activity is tightly controlled by counter-regulatory...
In physiological conditions, the gut is heavily infiltrated with various subsets of inflammatory cells, whose activity is tightly controlled by counter-regulatory mechanisms. Defects in such mechanisms can favour the development of chronic intestinal disorders, such as Crohn's disease (CD) and ulcerative colitis (UC), the principal forms of inflammatory bowel diseases (IBD) in humans, as well as systemic disorders. Over the last years, the frequency of intestinal and systemic immune-inflammatory disorders has increased in previously low incidence areas, likely due to the Westernization of lifestyles, including dietary habits. The Western diet is characterized by high consumption of proteins, saturated fats and sweets, as well as by a broad use of food additives (e.g., emulsifiers, bulking agents), which are used to preserve and enhance food quality. Accumulating evidence suggests that food additives can perturb gut homeostasis, thereby contributing to promote tissue-damaging inflammatory responses. For instance, mice given the emulsifiers carboxymethylcellulose and polysorbate 80 develop dysbiosis with overgrowth of mucus-degrading bacteria. Such an effect triggers colitis in animals deficient in either interleukin-10, a cytokine exerting anti-inflammatory and regulatory functions, or Toll-like receptor 5, a receptor recognizing the bacterial flagellin. Similarly, the polysaccharide maltodextrin induces endoplasmic reticulum stress in intestinal goblet cells, thereby impairing mucus release and increasing host susceptibility to colitis. In this review, we report and discuss the current knowledge about the impact of food additives on gut homeostasis and their potential contribution to the development of inflammatory disorders.
Topics: Animals; Colitis; Diet, Western; Dysbiosis; Food Additives; Gastrointestinal Microbiome; Homeostasis; Humans; Immunity, Mucosal; Intestines; Metabolic Diseases; Risk Assessment; Risk Factors
PubMed: 31581570
DOI: 10.3390/nu11102334 -
The Cochrane Database of Systematic... Jun 2018Cystic fibrosis (CF) is the most common, life-limiting, genetically inherited disease. It affects multiple organs, particularly the respiratory system. However,... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is the most common, life-limiting, genetically inherited disease. It affects multiple organs, particularly the respiratory system. However, gastrointestinal problems such as constipation and distal intestinal obstruction syndrome (DIOS) are also important and well-recognised complications in CF. They share similar symptoms e.g. bloating, abdominal pain, but are distinct conditions. Constipation occurs when there is gradual faecal impaction of the colon, but DIOS occurs when there is an accumulation of faeces and sticky mucus, forming a mass in the distal part of the small intestine. The mass may partially block the intestine (incomplete DIOS) or completely block the intestine (complete DIOS). Symptoms of DIOS can affect quality of life and other aspects of CF health, such as airway clearance, exercise, sleep and nutritional status. Treatment of constipation and prevention of complete bowel obstruction are required for gastrointestinal management in CF. However, many different strategies are used in clinical practice and there is a lack of consensus. The importance of this topic was highlighted in a recent research priority setting exercise by the James Lind Alliance.
OBJECTIVES
To evaluate the effectiveness and safety of laxative agents of differing types for preventing DIOS (complete and incomplete) in children and adults with CF.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of search: 22 May 2018.We also searched online trial registries. Date of last search: 10 June 2018.
SELECTION CRITERIA
Randomised and quasi-randomised controlled parallel trials comparing laxative therapy for preventing DIOS (including osmotic agents, stimulants, mucolytics and substances with more than one action) at any dose to placebo, no treatment or an alternative laxative therapy, in people of any age with pancreatic sufficient or insufficient CF and any stage of lung disease. Randomised cross-over trials were judged on an individual basis.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for inclusion, extracted outcome data and performed a risk of bias assessment for the included data. We judged the quality of the evidence using GRADE criteria.
MAIN RESULTS
We included one cross-over trial (17 participants) with a duration of 12 months, in which participants were randomly allocated to either cisapride (a gastro-prokinetic agent) or placebo for six months each. The trial had an unclear risk of bias for most domains but had a high risk of reporting bias.Radiograph scores revealed no difference in occurrence of DIOS between cisapride and placebo (narrative report, no data provided). There were no adverse effects. Symptom scores were the only secondary outcome within the review that were reported. Total gastrointestinal symptom scores favoured cisapride with a statistically significant mean difference (MD) of -7.60 (95% confidence interval (CI) -14.73 to -0.47). There was no significant difference at six months between cisapride and placebo for abdominal distension, MD -0.90 (95% CI -2.39 to 0.59) or abdominal pain, MD -0.4 (95% CI -2.05 to 1.25). The global symptom scores (whether individuals felt better or worse) were reported in the paper to favour cisapride and be statistically significant (P < 0.05).We assessed the available data to be very low quality. There was a great deal of missing data from the included trial and the investigators failed to report numerical data for many outcomes. The overall risk of bias of the trial was unclear and it had a high risk for reporting bias. There was also indirectness; the trial drug (cisapride) has since been removed from the market in several countries due to adverse effects, thus it has no current applicability for preventing DIOS. The included trial also had very few participants, which downgraded the quality a further level for precision.
AUTHORS' CONCLUSIONS
There is an absence of evidence for interventions for the prevention of DIOS. As there was only one included trial, we could not perform a meta-analysis of the data. Furthermore, the included trial compared a prokinetic agent (cisapride) that is no longer licensed for use in a number of countries due to the risk of serious cardiac events, a finding that came to light after the trial was conducted. Therefore, the limited findings from the trial are not applicable in current clinical practice.Overall, a great deal more research needs to be undertaken on gastrointestinal complications in CF, as this is a very poorly studied area compared to respiratory complications in CF.
Topics: Adolescent; Adult; Cisapride; Cystic Fibrosis; Gastrointestinal Agents; Humans; Intestinal Obstruction; Syndrome
PubMed: 29894558
DOI: 10.1002/14651858.CD012619.pub2 -
The Journal of Infectious Diseases Jul 2023Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection.
METHODS
EMBASE, PubMed, and Web of Science were searched (January 2000-December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types.
RESULTS
Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable.
CONCLUSIONS
RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.
Topics: Adult; Humans; Respiratory Syncytial Virus Infections; Sensitivity and Specificity; Respiratory Syncytial Virus, Human; Nasopharynx; Diagnostic Techniques and Procedures; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 36661222
DOI: 10.1093/infdis/jiad012 -
The Cochrane Database of Systematic... Apr 2016This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is... (Review)
Review
BACKGROUND
This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Topical (intranasal) corticosteroids are used with the aim of reducing inflammation in the sinonasal mucosa in order to improve patient symptoms.
OBJECTIVES
To assess the effects of different types of intranasal steroids in people with chronic rhinosinusitis.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing first-generation intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) with second-generation intranasal corticosteroids (e.g. ciclesonide, fluticasone furoate, fluticasone propionate, mometasone furoate, betamethasone sodium phosphate), or sprays versus drops, or low-dose versus high-dose intranasal corticosteroids.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis (nosebleed). Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse event of local irritation. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included nine RCTs (911 participants), including four different comparisons. None of the studies evaluated our first primary outcome measure, disease-specific HRQL. Fluticasone propionate versus beclomethasone dipropionate We identified two small studies (56 participants with polyps) that evaluated disease severity and looked at the primary adverse effect: epistaxis , but no other outcomes. We cannot report any numerical data but the study authors reported no difference between the two steroids. The evidence was of very low quality. Fluticasone propionate versus mometasone furoate We identified only one study (100 participants with polyps) that evaluated disease severity (nasal symptoms scores), which reported no difference (no numerical data available). The evidence was of very low quality. High-dose versus low-dose steroidsWe included five studies (663 participants with nasal polyps), three using mometasone furoate (400 µg versus 200 µg in adults and older children, 200 µg versus 100 µg in younger children) and two using fluticasone propionate drops (800 µg versus 400 µg). We found low quality evidence relating to disease severity and nasal polyps size, with results from the high-dose and low-dose groups being similar. Although all studies reported more improvement in polyp score in the high-dose group, the significance of this is unclear due to the small size of the improvements.The primary adverse effect, epistaxis , was more common when higher doses were used (risk ratio (RR) 2.06, 95% confidence interval (CI) 1.20 to 3.54, 637 participants, moderate quality evidence). Most of the studies that contributed data to this outcome used a broad definition of epistaxis, which ranged from frank bleeding to bloody nasal discharge to flecks of blood in the mucus. Aqueous nasal spray versus aerosol spray We identified only one poorly reported study (unclear number of participants for comparison of interest, 91 between three treatment arms), in which there were significant baseline differences between the participants in the two groups. We were unable to draw meaningful conclusions from the data.
AUTHORS' CONCLUSIONS
We found insufficient evidence to suggest that one type of intranasal steroid is more effective than another in patients with chronic rhinosinusitis, nor that the effectiveness of a spray differs from an aerosol. We identified no studies that compared drops with spray.It is unclear if higher doses result in better symptom improvements (low quality evidence), but there was moderate quality evidence of an increased risk of epistaxis as an adverse effect of treatment when higher doses were used. This included all levels of severity of epistaxis and it is likely that the proportion of events that required patients to discontinue usage is low due to the low numbers of withdrawals attributed to it. If epistaxis is limited to streaks of blood in the mucus it may be tolerated by the patient and it may be safe to continue treatment. However, it may be a factor that affects compliance.There is insufficient evidence to suggest that the different types of corticosteroid molecule or spray versus aerosol have different effects. Lower doses have similar effectiveness but fewer side effects.Clearly more research in this area is needed, with specific attention given to trial design, disease-specific health-related quality of life outcomes and evaluation of longer-term outcomes and adverse effects.
Topics: Administration, Intranasal; Adult; Beclomethasone; Child; Chronic Disease; Fluticasone; Humans; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis; Steroids
PubMed: 27115215
DOI: 10.1002/14651858.CD011993.pub2 -
The Cochrane Database of Systematic... Jul 2016People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs. Repeated infections often cause lung damage and disease.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (also known as ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review.
OBJECTIVES
To compare the clinical effectiveness of the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 25 April 2016.
SELECTION CRITERIA
Randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study.
MAIN RESULTS
Our search identified 62 studies, of which 19 (440 participants) met the inclusion criteria. Five randomised controlled studies (192 participants) were included in the meta-analysis; three were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 22.33 years). In 13 studies, follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis.Included studies compared the active cycle of breathing technique with autogenic drainage, airway oscillating devices, high frequency chest compression devices, conventional chest physiotherapy, and positive expiratory pressure. Preference of technique varied: more participants preferred autogenic drainage over the active cycle of breathing technique; more preferred the active cycle of breathing technique over airway oscillating devices; and more were comfortable with the active cycle of breathing technique versus high frequency chest compression. No significant difference was seen in quality of life, sputum weight, exercise tolerance, lung function, or oxygen saturation between the active cycle of breathing technique and autogenic drainage or between the active cycle of breathing technique and airway oscillating devices. There was no significant difference in lung function and the number of pulmonary exacerbations between the active cycle of breathing technique alone or in conjunction with conventional chest physiotherapy. All other outcomes were either not measured or had insufficient data for analysis.
AUTHORS' CONCLUSIONS
There is insufficient evidence to support or reject the use of the active cycle of breathing technique over any other airway clearance therapy. Five studies, with data from eight different comparators, found that the active cycle of breathing technique was comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of the active cycle of breathing technique on outcomes important for people with cystic fibrosis such as quality of life and preference.
Topics: Chest Wall Oscillation; Cystic Fibrosis; Drainage, Postural; High-Frequency Ventilation; Humans; Patient Preference; Randomized Controlled Trials as Topic; Respiratory Therapy
PubMed: 27378490
DOI: 10.1002/14651858.CD007862.pub4