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The Cochrane Database of Systematic... Apr 2013Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems.
OBJECTIVES
To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012.
SELECTION CRITERIA
Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached.
MAIN RESULTS
The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Nebulisers using adaptive aerosol delivery or vibrating mesh technology reduce treatment time to a far greater extent. Deposition (as a percentage of priming dose) is greater than conventional with adaptive aerosol delivery. Vibrating mesh technology systems may give greater deposition than conventional when measuring sputum levels, but lower deposition when measuring serum levels or using gamma scintigraphy. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved with systems which use these newer technologies, but also that some nebuliser systems using vibrating mesh technology may be subject to increased failures.
AUTHORS' CONCLUSIONS
Clinicians should be aware of the variability in the performance of different nebuliser systems. Technologies such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, patient preference and adherence. There is a need for long-term randomised controlled trials of these technologies to determine patient-focused outcomes (such as quality of life and burden of care), safe and effective dosing levels of medications and clinical outcomes (such as hospitalisations and need for antibiotics) and an economic evaluation of their use.
Topics: Aerosols; Albuterol; Anti-Bacterial Agents; Bronchodilator Agents; Carbenicillin; Colistin; Cromolyn Sodium; Cystic Fibrosis; Deoxyribonuclease I; Drug Delivery Systems; Humans; Medication Adherence; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Recombinant Proteins; Saline Solution, Hypertonic; Tobramycin
PubMed: 23633344
DOI: 10.1002/14651858.CD007639.pub2 -
The Cochrane Database of Systematic... Nov 2012Bronchiolitis is one of the most common respiratory problems in the first year of life. The sputum of infants with bronchiolitis has increased deoxyribonucleic acid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is one of the most common respiratory problems in the first year of life. The sputum of infants with bronchiolitis has increased deoxyribonucleic acid (DNA) content, leading to mucous plugging and airway obstruction. Recombinant human deoxyribonuclease (rhDNase), an enzyme that digests extracellular DNA, might aid the clearance of mucus and relieve peripheral airway obstruction.
OBJECTIVES
To determine the effect of nebulised rhDNase on the severity and duration of viral bronchiolitis in children younger than 24 months of age in the hospital setting.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2012, Issue 7 which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to July Week 4, 2012), EMBASE (1974 to August 2012) and LILACS (1982 to August 2012).
SELECTION CRITERIA
Randomised controlled trials (RCTs) using nebulised rhDNase alone or with concomitant therapy in children younger than 24 months of age hospitalised with acute bronchiolitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed literature searches, assessed trial quality and extracted data. We obtained unpublished data from trial authors. We used Review Manager 5.1 to pool treatment effects expressed as the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI).
MAIN RESULTS
Three RCTs (333 participants) were identified, two of which were multicentre trials comprising only participants positive for respiratory syncytial virus (RSV). The other trial enrolled participants clinically diagnosed with bronchiolitis from a hospital in Italy. All studies used 2.5 mL (1 mg/mL) of nebulised rhDNase compared with placebo either as a daily or a twice daily dose. Adjunctive therapy included nebulised salbutamol, steroids, supplemental oxygen, intravenous fluids or tube feeding, nasal washing, nasal decongestants and antibiotics.Overall, nebulised rhDNase showed no benefit in clinically meaningful outcomes. Meta-analysis favoured the control group with a shorter duration of hospital stay (MD 0.50; 95% CI 0.10 to 0.90, P = 0.01) and better clinical score improvement (SMD -0.24; 95% CI -0.50 to 0.01, P = 0.06). The largest trial showed no difference in supplemental oxygen use or intensive care unit (ICU) admission.In one RCT, four out of 11 patients in the treatment group had atelectasis. Two of these patients showed distinctive clinical improvement after nebulised rhDNase.There was no significant difference in adverse events. These included temporary desaturation, temporary coughing, increased coughing, facial rash, hoarseness, dyspnoea and bad taste, reported in a total of 11 patients from both treatment groups.
AUTHORS' CONCLUSIONS
The results based on the three included studies in this review did not support the use of nebulised rhDNase in children under 24 months of age hospitalised with acute bronchiolitis. In these patients, treatment did not shorten the length of hospitalisation or improve clinical outcomes. It might have a role in severe bronchiolitis complicated by atelectasis, but further clinical studies would need to be performed.
Topics: Administration, Inhalation; Bronchiolitis, Viral; Deoxyribonucleases; Humans; Infant; Nebulizers and Vaporizers; Pulmonary Atelectasis; Randomized Controlled Trials as Topic
PubMed: 23152257
DOI: 10.1002/14651858.CD008395.pub2 -
The Cochrane Database of Systematic... Oct 2012Tracheomalacia, a disorder of the large airways where the trachea is deformed or malformed during respiration, is commonly seen in tertiary paediatric practice. It is... (Review)
Review
BACKGROUND
Tracheomalacia, a disorder of the large airways where the trachea is deformed or malformed during respiration, is commonly seen in tertiary paediatric practice. It is associated with a wide spectrum of respiratory symptoms from life-threatening recurrent apnoea to common respiratory symptoms such as chronic cough and wheeze. Current practice following diagnosis of tracheomalacia includes medical approaches aimed at reducing associated symptoms of tracheomalacia, ventilation modalities of continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP), and surgical approaches aimed at improving the calibre of the airway (airway stenting, aortopexy, tracheopexy).
OBJECTIVES
To evaluate the efficacy of medical and surgical therapies for children with intrinsic (primary) tracheomalacia.
SEARCH METHODS
The Cochrane Airways Group searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Airways Group's Specialised Register, MEDLINE and EMBASE databases. The Cochrane Airways Group performed the latest searches in March 2012.
SELECTION CRITERIA
All randomised controlled trials (RCTs) of therapies related to symptoms associated with primary or intrinsic tracheomalacia.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data from the included study independently and resolved disagreements by consensus.
MAIN RESULTS
We included one RCT that compared nebulised recombinant human deoxyribonuclease (rhDNase) with placebo in 40 children with airway malacia and a respiratory tract infection. We assessed it to be a RCT with overall low risk of bias. Data analysed in this review showed that there was no significant difference between groups for the primary outcome of proportion cough-free at two weeks (odds ratio (OR) 1.38; 95% confidence interval (CI) 0.37 to 5.14). However, the mean change in night time cough diary scores significantly favoured the placebo group (mean difference (MD) 1.00; 95% CI 0.17 to 1.83, P = 0.02). The mean change in daytime cough diary scores from baseline was also better in the placebo group compared to those on nebulised rhDNase, but the difference between groups was not statistically significant (MD 0.70; 95% CI -0.19 to 1.59). Other outcomes (dyspnoea, and difficulty in expectorating sputum scores, and lung function tests at two weeks also favoured placebo over nebulised rhDNase but did not reach levels of significance.
AUTHORS' CONCLUSIONS
There is currently an absence of evidence to support any of the therapies currently utilised for management of intrinsic tracheomalacia. It remains inconclusive whether the use of nebulised rhDNase in children with airway malacia and a respiratory tract infection worsens recovery. It is unlikely that any RCT on surgically based management will ever be available for children with severe life-threatening illness associated with tracheomalacia. For those with less severe disease, RCTs on interventions such as antibiotics and chest physiotherapy are clearly needed. Outcomes of these RCTs should include measurements of the trachea and physiological outcomes in addition to clinical outcomes.
Topics: Administration, Inhalation; Adolescent; Child; Child, Preschool; Cough; Deoxyribonucleases; Dyspnea; Humans; Randomized Controlled Trials as Topic; Tracheomalacia
PubMed: 23076914
DOI: 10.1002/14651858.CD005304.pub3 -
Chest Aug 2012The purpose of our study was to conduct a systematic review and meta-analysis of all randomized controlled trials to date comparing fibrinolytics with placebo to clarify... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of our study was to conduct a systematic review and meta-analysis of all randomized controlled trials to date comparing fibrinolytics with placebo to clarify their current role in the management of parapneumonic effusions and empyemas.
METHODS
MEDLINE, EMBASE, PapersFirst, and the Cochrane Collaboration and the Cochrane Register of controlled trials were searched. All searches were inclusive as of October 2011. Two investigators independently reviewed articles and extracted data. Quality was assessed with the Cochrane concealment of allocation approach and the Jadad criteria.
RESULTS
Seven randomized controlled studies (total number of patients, 801) comparing fibrinolytic therapy with placebo were included in the meta-analysis. Fibrinolytic therapy was beneficial for the outcomes of treatment failure (surgical intervention or death) (risk ratio [RR], 0.50; 95% CI, 0.28-0.87) and surgical intervention alone (RR, 0.61; 95% CI, 0.45-0.82). There was no difference in mean duration of hospital stay (standard mean difference, -0.69; 95% CI, -1.54-0.16) or death (RR, 1.14; 95% CI, 0.74-1.74).
CONCLUSIONS
This meta-analysis does reveal that fibrinolytic therapy is potentially beneficial in the management of parapneumonic effusions and empyemas in the adult population. Although there is insufficient evidence to support the routine use of this therapy for all parapneumonic effusions/empyemas, fibrinolytic therapy may be considered in patients with loculated pleural effusions, because it may prevent the need for surgical intervention. Further randomized controlled trials with adequate power are needed to definitively address the effect of fibrinolytics and the combination of fibrinolytics and deoxyribonuclease on the clinical outcomes outlined in this analysis in patients with parapneumonic effusions/empyemas.
Topics: Adult; Empyema, Pleural; Fibrinolytic Agents; Humans; Pleural Effusion; Randomized Controlled Trials as Topic; Thrombolytic Therapy; Treatment Outcome
PubMed: 22459772
DOI: 10.1378/chest.11-3071 -
Journal of Periodontology Sep 2012The purpose of the meta-analysis is to explore the association between vitamin D receptor polymorphisms (including four gene loci: Taq-I, Bsm-I, Apa-I, and Fok-I) for... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The purpose of the meta-analysis is to explore the association between vitamin D receptor polymorphisms (including four gene loci: Taq-I, Bsm-I, Apa-I, and Fok-I) for susceptibility to periodontitis (either chronic [CP] or aggressive [AP]). Up to now, there has been only one systematic review focusing on this topic. We obtained some different findings compared with the previously published literature.
METHODS
Nineteen case-control studies were identified through a search of multiple electronic databases (from January 1, 1999 to June 30, 2011). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) using codominant, dominant, and recessive genetic models from meta-analysis were the main outcome measure. The Harbord test was used to detect the publication bias for each group.
RESULTS
Eighteen identified articles met the eligibility criteria. Through overall analyses, no statistical association was found between polymorphisms of the four gene loci and periodontitis. However, based on subgroup analyses, a significant association between the Taq-I variants and CP rather than AP was shown in Asians (OR = 0.590; 95% CI = 0.425, 0.818) but not in whites (OR = 0.823; 95% CI = 0.637, 1.063). No statistically significant association was found between polymorphisms of Bsm-I and Apa-I with either AP or CP. The Fok-I polymorphism showed a statistical association with AP (OR = 1.583; 95% CI = 1.157, 2.166) instead of CP (OR = 1.081; 95% CI = 0.638, 1.830) in Asians.
CONCLUSIONS
The results of the present meta-analysis indicate the following: 1) the mutant allele t of the Taq-I locus may be a protective factor for CP but not for AP in Asians, although this was not true in whites; 2) the mutant allele F of the Fok-I locus appeared to be a risk factor for AP rather than CP in Asians; and 3) Bsm-I and Apa-I polymorphisms were found to have no significant associations with susceptibility to periodontitis (CP/AP).
Topics: Aggressive Periodontitis; Alleles; Asian People; Case-Control Studies; Chromosome Mapping; Chronic Periodontitis; Deoxyribonucleases, Type II Site-Specific; Genes, Dominant; Genes, Recessive; Genetic Predisposition to Disease; Humans; Mutation; Periodontitis; Polymorphism, Genetic; Receptors, Calcitriol; Risk Factors; Thymine; White People
PubMed: 22181683
DOI: 10.1902/jop.2011.110518 -
BMJ Clinical Evidence Aug 2011Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent.... (Review)
Review
INTRODUCTION
Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent. Bronchiectasis may cause signs of chronic obstructive pulmonary disease. It can also be associated with cystic fibrosis and other congenital disorders, foreign body inhalation, and other causes of lung damage.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions.
RESULTS
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergic therapy, beta(2) agonists, bronchopulmonary hygiene physical therapy, corticosteroids (inhaled, oral), exercise or physical training, hyperosmolar agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral), mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, and surgery.
Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Bronchiectasis; Cystic Fibrosis; Humans; Leukotriene Antagonists; Lung
PubMed: 21846412
DOI: No ID Found -
The Cochrane Database of Systematic... May 2011Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis.
OBJECTIVES
To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day).
SEARCH STRATEGY
Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international CF conference proceedings.Search date: 6 October 2010.
SELECTION CRITERIA
Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study 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 92 trial reports representing 47 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change FEV(1). Similarly, FVC and quality of life were not significantly affected; FEF(25) was significantly worse with dornase alfa inhalation after airway clearance, MD -0.17 litres (95% CI -0.28 to -0.05), based on the pooled data from two small studies in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms.
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 studies with variable follow-up. Apart from this, 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; Respiratory Therapy; Time Factors; Young Adult
PubMed: 21563162
DOI: 10.1002/14651858.CD007923.pub2 -
The Cochrane Database of Systematic... May 2011Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue will expedite wound healing. There... (Review)
Review
BACKGROUND
Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue will expedite wound healing. There are numerous methods available but no consensus on which one is most effective for surgical wounds.
OBJECTIVES
To determine the effect of different methods of debridement on the rate of debridement and healing of surgical wounds.
SEARCH STRATEGY
For this second update we searched the Cochrane Wounds Group Specialised Register (searched 13 April 2011); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1); Ovid MEDLINE (2007 to March Week 5 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, April 11, 2011); Ovid EMBASE (2007 to 2011 Week 14); and EBSCO CINAHL (2007 to 8 April 2011).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with outcomes including at least one of the following: time to complete debridement or time to complete healing.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the abstracts and titles obtained from the search, extracted data independently using a standardised extraction sheet and independently assessed methodological quality. One review author was involved in all stages of the data collection and extraction process, thus ensuring continuity.
MAIN RESULTS
Five RCTs (159 participants) were eligible for inclusion; all compared treatments for infected surgical wounds and reported time required to achieve a clean wound bed (complete debridement). One trial compared an enzymatic agent (streptokinase/streptodornase) with saline-soaked dressings. Four trials compared the effectiveness of dextranomer beads or paste with other products (different comparator in each trial) to achieve complete debridement. Meta-analysis was not possible due to the unique comparisons within each trial. One trial reported that dextranomer achieved a clean wound bed significantly more quickly than Eusol, and one trial comparing enzymatic debridement with saline-soaked dressings reported that the enzyme-treated wounds were cleaned more quickly. However, methodological quality was poor in these two trials.
AUTHORS' CONCLUSIONS
There is a lack of large, high-quality published RCTs evaluating debridement per se, or comparing different methods of debridement for surgical wounds, to guide clinical decision-making.
Topics: Debridement; Dextrans; Humans; Randomized Controlled Trials as Topic; Streptodornase and Streptokinase; Surgical Wound Infection; Wound Healing
PubMed: 21563150
DOI: 10.1002/14651858.CD006214.pub3 -
The Cochrane Database of Systematic... Mar 2010Dornase alfa is currently used to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dornase alfa is currently used to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis.
OBJECTIVES
To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other mucolytics and to identify any adverse events associated with its use.
SEARCH STRATEGY
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences.Date of the most recent search of the Group's Cystic Fibrosis Register: 17 July 2009.
SELECTION CRITERIA
All randomised and quasi-randomised controlled trials where dornase alfa was compared to placebo, standard therapy or another mucolytic.
DATA COLLECTION AND ANALYSIS
Authors independently assessed trials for inclusion criteria; the lead author and a colleague carried out analysis of methodological quality and data extraction.
MAIN RESULTS
The searches identified 43 trials, of which 15 met our inclusion criteria, including a total of 2469 participants. Three additional studies examined the healthcare cost from one of the clinical trials. Twelve studies compared dornase alfa to placebo or no dornase alfa treatment; one compared daily dornase alfa with hypertonic saline and alternate day dornase alfa; and two compared daily dornase alfa to hypertonic saline. Study duration varied from six days to two years. The number of deaths was not significant between treatment groups. Spirometric lung function improved in the treated groups, with significant differences at one month, three months, six months and two years, there was a non-significant difference at three years. There was no excess of adverse effects except voice alteration and rash, which were reported more frequently in one trial in the treated groups. Insufficient data were available to analyse differences in antibiotic treatment, inpatient stay and quality of life.
AUTHORS' CONCLUSIONS
There is evidence to show that therapy with dornase alfa over a one-month period is associated with an improvement in lung function in CF; results from a trial lasting six months also showed the same effect. Therapy over a two-year period (based on one trial) significantly improved FEV(1) in children and there was a non-significant reduction in the risk of infective exacerbations. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials.
Topics: Adolescent; Child; Child, Preschool; Cystic Fibrosis; Deoxyribonuclease I; Expectorants; Humans; Infant; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic
PubMed: 20238314
DOI: 10.1002/14651858.CD001127.pub2 -
Cancer Epidemiology, Biomarkers &... Nov 2009Low levels of plasma vitamin D have been implicated as a possible risk factor for both prostate cancer incidence and advanced disease, and recent phase II trials suggest... (Review)
Review
Genetic variants in the vitamin d receptor are associated with advanced prostate cancer at diagnosis: findings from the prostate testing for cancer and treatment study and a systematic review.
Low levels of plasma vitamin D have been implicated as a possible risk factor for both prostate cancer incidence and advanced disease, and recent phase II trials suggest that vitamin D supplementation might delay progression of prostate cancer. Common polymorphisms in the vitamin D receptor (VDR) are associated with VDR activity and are therefore potentially useful proxies for assessing whether vitamin D is causally related to advanced prostate cancer. We genotyped five well-known VDR polymorphisms in 1,604 men with prostate cancer from the Prostate Testing for Cancer and Treatment study. Our aim was to examine the association between VDR polymorphisms and cancer stage (localized versus advanced) as well as cancer grade (Gleason score <7 versus >or=7). Moreover, we also carried out a systematic review and meta-analysis of 13 similar studies. As a result of our meta-analysis, we revealed three polymorphisms, BsmI, ApaI, and TaqI, associated with high Gleason score with an overall summary odds ratios (95% confidence intervals) of 1.12 (1.00-1.25; bb versus BB + Bb), 1.25 (1.02-1.53; aa versus AA + Aa), and 0.82 (0.69-0.98; Tt + tt versus TT), respectively. The haplotype analysis revealed that the BsmI (B)-ApaI (A)-TaqI (t) participants compared with BsmI (b)-ApaI (a)-TaqI (T) individuals were less likely to have high Gleason scores (odds ratio, 0.84; 95% confidence interval, 0.71-1.00; P(unadjusted) = 0.050; P(adjusted) = 0.014). Our finding provides some support for the hypothesis that low levels of vitamin D may increase the risk of prostate cancer progression.
Topics: Aged; DNA Restriction Enzymes; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Middle Aged; Neoplasm Staging; Odds Ratio; Polymorphism, Genetic; Prognosis; Prostatic Neoplasms; Receptors, Calcitriol; Risk Factors; United Kingdom
PubMed: 19861519
DOI: 10.1158/1055-9965.EPI-09-0544