Beta-blocker use and COPD mortality: a systematic review and meta-analysis

ABSTRACT: BACKGROUND: Despite the benefits of beta-blockers in patients with established or sub-clinical coronary artery disease, their use in patients with chronic obstructive pulmonary disease (COPD) has been controversial. Currently, no systematic review has examined the impact of beta-blockers on mortality in COPD. METHODS: We systematically searched electronic bibliographic databases including MEDLINE, EMBASE and Cochrane Library for clinical studies that examine the association between beta-blocker use and all cause mortality in patients with COPD. Risk ratios across studies were pooled using random effects models to estimate a pooled relative risk across studies. Publication bias was assessed using a funnel plot. RESULTS: Our search identified nine retrospective cohort studies that met the study inclusion criteria. The pooled relative risk of COPD related mortality secondary to beta-blocker use was 0.69 (95% CI: 0.62-0.78; I2=82%). CONCLUSION: The results of this review are consistent with a protective effect of beta-blockers with respect to all cause mortality. Due to the observational nature of the included studies, the possibility of confounding that may have affected these results cannot be excluded. The hypothesis that beta blocker therapy might be of benefit in COPD needs to be evaluated in randomised controlled trials.     

Pulmonary biomarkers in COPD exacerbations: a systematic review

Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems. Innovative sampling techniques have led to the identification of several pulmonary biomarkers. Although some molecules are promising, their usefulness in clinical practice is not yet established. Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD. We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method. Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further. Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment. According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels. Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis. Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited. In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes. However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use. Clinical trials that incorporate biomarkers in decisional algorithms are required.     

Daily average temperature and mortality among the elderly: a meta-analysis and systematic review of epidemiological evidence

The impact of climate change on the health of vulnerable groups such as the elderly has been of increasing concern. However, to date there has been no meta-analysis of current literature relating to the effects of temperature fluctuations upon mortality amongst the elderly. We synthesised risk estimates of the overall impact of daily mean temperature on elderly mortality across different continents. A comprehensive literature search was conducted using MEDLINE and PubMed to identify papers published up to December 2010. Selection criteria including suitable temperature indicators, endpoints, study-designs and identification of threshold were used. A two-stage Bayesian hierarchical model was performed to summarise the percent increase in mortality with a 1°C temperature increase (or decrease) with 95% confidence intervals in hot (or cold) days, with lagged effects also measured. Fifteen studies met the eligibility criteria and almost 13 million elderly deaths were included in this meta-analysis. In total, there was a 2-5% increase for a 1°C increment during hot temperature intervals, and a 1-2 % increase in all-cause mortality for a 1°C decrease during cold temperature intervals. Lags of up to 9 days in exposure to cold temperature intervals were substantially associated with all-cause mortality, but no substantial lagged effects were observed for hot intervals. Thus, both hot and cold temperatures substantially increased mortality among the elderly, but the magnitude of heat-related effects seemed to be larger than that of cold effects within a global context.     

Toxocariasis and epilepsy: systematic review and meta-analysis

Objective

Human toxocariasis is a zoonotic infection caused by the larval stages of Toxocara canis (T. canis) and less frequently Toxocara cati (T. cati). A relationship between toxocariasis and epilepsy has been hypothesized. We conducted a systematic review and a meta-analysis of available data to evaluate the strength of association between epilepsy and Toxocara spp. seropositivity and to propose some guidelines for future surveys.

Data Sources

Electronic databases, the database from the Institute of Neuroepidemiology and Tropical Neurology of the University of Limoges (http://www-ient.unilim.fr/) and the reference lists of all relevant papers and books were screened up to October 2011.

Methods

We performed a systematic review of literature on toxocariasis (the exposure) and epilepsy (the outcome). Two authors independently assessed eligibility and study quality and extracted data. A common odds ratio (OR) was estimated using a random-effects meta-analysis model of aggregated published data.

Results

Seven case-control studies met the inclusion criteria, for a total of 1867 participants (850 cases and 1017 controls). The percentage of seropositivity (presence of anti-Toxocara spp. antibodies) was higher among people with epilepsy (PWE) in all the included studies even if the association between epilepsy and Toxocara spp. seropositivity was statistically significant in only 4 studies, with crude ORs ranging 2.04–2.85. Another study bordered statistical significance, while in 2 of the included studies no significant association was found. A significant (p<0.001) common OR of 1.92 [95% confidence interval (CI) 1.50–2.44] was estimated. Similar results were found when meta-analysis was restricted to the studies considering an exclusively juvenile population and to surveys using Western Blot as confirmatory or diagnostic serological assay.

Conclusion

Our results support the existence of a positive association between Toxocara spp. seropositivity and epilepsy. Further studies, possibly including incident cases, should be performed to better investigate the relationship between toxocariasis and epilepsy.     

Statins reduce all-cause mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis of observational studies

Background

Recent observational studies have suggested that use of statins reduces mortality in patients suffering from chronic obstructive pulmonary disease. However, no meta-analysis has reported the pooled hazard ratio of statins to all-cause mortality.

Methods

We searched for eligible articles using five databases. We included randomized controlled trials and cohort studies written in English using original data reporting the hazard ratio of statins to all-cause, cardiovascular-related, cancer-related, or respiratory-related mortality. A fixed model with the confidence interval method was used. Publication bias was evaluated by funnel plot and Begg’s test, and was corrected using Duval’s trim and fill method. Sensitivity analyses were also conducted.

Results

We included 10 out of 128 articles. The pooled hazard ratio of statins to all-cause mortality involving 16269 patients was 0.81 (95% CI: 0.75-0.86, P < 0.001) with moderate heterogeneity (I2 = 52%, P = 0.032). The sensitivity analysis and funnel plot suggested the existence of publication bias. After three possibly unpublished cohorts were imputed, the pooled hazard ratio of 0.83 (95% CI: 0.78-0.88, P < 0.001) still suggested a favorable prognosis in statin-treated patients. The pooled hazard ratio of statins to cardiovascular-related, cancer-related, and respiratory-related mortality were 0.52 (95% CI: 0.27-1.01, P = 0.052), 0.57 (95% CI: 0.32-1.01, P = 0.056), and 0.55 (95% CI: 0.43-0.78, P < 0.001), respectively, although these results were not conclusive as we could not find a sufficient number of original studies dealing with those forms of mortality.

Conclusions

The use of statins for patients suffering from chronic obstructive pulmonary disease may reduce all-cause mortality. This conclusion should be re-evaluated by a registered large-scale randomized controlled trial.     

Post-stroke infection: A systematic review and meta-analysis

Background  

stroke is the main cause of disability in high-income countries, and ranks second as a cause of death worldwide. Patients with acute stroke are at risk for infections, but reported post-stroke infection rates vary considerably. We performed a systematic review and meta-analysis to estimate the pooled post-stroke infection rate and its effect on outcome.     

Effect of early surgery after hip fracture on mortality and complications: systematic review and meta-analysis

Background

Guidelines exist for the surgical treatment of hip fracture, but the effect of early surgery on mortality and other outcomes that are important for patients remains unclear. We conducted a systematic review and meta-analysis to determine the effect of early surgery on the risk of death and common postoperative complications among elderly patients with hip fracture.

Methods

We searched electronic databases (including MEDLINE and EMBASE), the archives of meetings of orthopedic associations and the bibliographies of relevant articles and questioned experts to identify prospective studies, published in any language, that evaluated the effects of early surgery in patients undergoing procedures for hip fracture. Two reviewers independently assessed methodologic quality and extracted relevant data. We pooled data by means of the DerSimonian and Laird random-effects model, which is based on the inverse variance method.

Results

We identified 1939 citations, of which 16 observational studies met our inclusion criteria. These studies had a total of 13 478 patients for whom mortality data were complete (1764 total deaths). Based on the five studies that reported adjusted risk of death (4208 patients, 721 deaths), irrespective of the cut-off for delay (24, 48 or 72 hours), earlier surgery (i.e., within the cut-off time) was associated with a significant reduction in mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68–0.96, p = 0.01). Unadjusted data indicated that earlier surgery also reduced in-hospital pneumonia (RR 0.59, 95% CI 0.37–0.93, p = 0.02) and pressure sores (RR 0.48, 95% CI 0.34–0.69, p < 0.001).

Interpretation

Earlier surgery was associated with a lower risk of death and lower rates of postoperative pneumonia and pressure sores among elderly patients with hip fracture. These results suggest that reducing delays may reduce mortality and complications.Among elderly patients, hip fracture is associated with a one-year mortality rate ranging from 14% to 36%¹ and also with profound temporary and sometimes permanent impairment of independence and quality of life.² As the elderly population increases, the annual number of hip fractures globally is expected to exceed 7 million over the next 40 to 50 years.³Current guidelines⁴ indicate that surgery for hip fracture should be performed within 24 hours of injury, as earlier surgery has been associated with better functional outcome, shorter hospital stay, shorter duration of pain and lower rates of nonunion, postoperative complications and mortality.^5–11Proponents of early treatment argue that this approach minimizes the length of time a patient is confined to bed rest, thereby reducing the risk of associated complications, such as pressure sores, deep vein thrombosis and urinary tract infections.⁸ However, those favouring a delay believe it provides the opportunity to optimize patients’ medical status, thereby decreasing the risk of perioperative complications.⁸ A further challenge to resolving the debate is the lack of an accepted definition of early surgery.¹² Uncertainty exists about whether 24, 48 or 72 hours, or a longer period, should be considered to represent an “unacceptable delay” for hip fracture surgery.We undertook a systematic review and meta-analysis to inform this debate. More specifically, we addressed the following question: Among patients 60 years of age or older who underwent surgery for hip fracture, what was the effect of early surgery, relative to delayed surgery, on all-cause mortality and postoperative complications?     

Molecular typing of Treponema pallidum: a systematic review and meta-analysis

Background

Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance.

Methodology/Principal Findings

Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included “Treponema pallidum,” or “syphilis,” combined with the subject headings “molecular,” “subtyping,” “typing,” “genotype,” and “epidemiology.” Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, χ² = 247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ² = 102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited.

Conclusions/Significance

Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the relationship between clinical presentation and subtype, and further validation of ear lobe blood for obtaining T. pallidum DNA would be useful for future molecular studies of syphilis.     

Pharmacotherapy in pulmonary arterial hypertension: a systematic review and meta-analysis

Background

Previous meta-analyses of treatments for pulmonary arterial hypertension (PAH) have not shown mortality benefit from any individual class of medication.

Methods

MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through November 2009 for randomized trials that evaluated any pharmacotherapy in the treatment of PAH. Reference lists from included articles and recent review articles were also searched. Analysis included randomized placebo controlled trials of at least eight weeks duration and studies comparing intravenous medication to an unblinded control group.

Results

1541 unique studies were identified and twenty-four articles with 3758 patients were included in the meta-analysis. Studies were reviewed and data extracted regarding study characteristics and outcomes. Data was pooled for three classes of medication: prostanoids, endothelin-receptor antagonists (ERAs), and phosphodiesterase type 5 (PDE5) inhibitors. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for mortality, 6-minute walk distance, dyspnea scores, hemodynamic parameters, and adverse effects. Mortality in the control arms was a combined 4.2% over the mean study length of 14.9 weeks. There was significant mortality benefit with prostanoid treatment (RR 0.49, CI 0.29 to 0.82), particularly comparing intravenous agents to control (RR 0.30, CI 0.14 to 0.63). Mortality benefit was not observed for ERAs (RR 0.58, CI 0.21 to 1.60) or PDE5 inhibitors (RR 0.30, CI 0.08 to 1.08). All three classes of medication improved other clinical and hemodynamic endpoints. Adverse effects that were increased in treatment arms include jaw pain, diarrhea, peripheral edema, headache, and nausea in prostanoids; and visual disturbance, dyspepsia, flushing, headache, and limb pain in PDE5 inhibitors. No adverse events were significantly associated with ERA treatment.

Conclusions

Treatment of PAH with prostanoids reduces mortality and improves multiple other clinical and hemodynamic outcomes. ERAs and PDE5 inhibitors improve clinical and hemodynamic outcomes, but have no proven effect on mortality. The long-term effects of all PAH treatment requires further study.     

Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis

Many randomized clinical controlled trials have confirmed the efficacy and safety of calcium dobesilate in treating diabetic retinopathy(DR).This systematic review critically evaluated the evidence that links calcium dobesilate to DR.In this fixed-effects meta-analysis,a total of 221 pertinent English-language articles published between January 1975 and October 2013 were identified.Systematic searches of PUBMED,Springer Link and the Cochrane Clinical Trials Database were conducted using the keywords “diabetic retinopathy” and “calcium dobesilate”.The extracted information included the study design,inclusion and exclusion criteria,setting,sample size,participant mean age,treatment regime,mean change in best corrected visual acuity,laboratory parameters,capillary fragility,intraocular pressure and fundus manifestations based on the findings of fluorescent angiography.The summary statistics indicated that calcium dobesilate was significantly associated with improving retinal microaneurysms(RR: 0.62,95%CI: 0.42?0.90,P=0.01),retinalhemorrhages(RR: 0.39,95% CI: 0.17?0.88,P=0.02); exudates(RR: 0.31,95% CI: 0.12?0.81,P=0.02),reduction of whole blood viscosity(MD: ?0.57 CP,95% CI: ?0.75 to ?0.38,P<0.001),plasma viscosity(MD: ?0.36 CP,95% CI: ?0.63 to ?0.09,P=0.01) and blood cholesterol(MD: ?0.48 mg m L?1,95% CI: ?0.64?0.33,P<0.00001).Intraocular pressure was also significantly reduced(MD: ?5.59 mm Hg,95% CI: ?6.69 to ?4.50,P<0.00001).The results indicate that calcium dobesilate effectively treats DR at the systematic and local ocular levels.     

Derivation and validation of clinical phenotypes for COPD: a systematic review

Background

The traditional classification of COPD, which relies solely on spirometry, fails to account for the complexity and heterogeneity of the disease. Phenotyping is a method that attempts to derive a single or combination of disease attributes that are associated with clinically meaningful outcomes. Deriving phenotypes entails the use of cluster analyses, and helps individualize patient management by identifying groups of individuals with similar characteristics. We aimed to systematically review the literature for studies that had derived such phenotypes using unsupervised methods.

Methods

Two independent reviewers systematically searched multiple databases for studies that performed validated statistical analyses, free of definitive pre-determined hypotheses, to derive phenotypes among patients with COPD. Data were extracted independently.

Results

9156 citations were retrieved, of which, 8 studies were included. The number of subjects ranged from 213 to 1543. Most studies appeared to be biased: patients were more likely males, with severe disease, and recruited in tertiary care settings. Statistical methods used to derive phenotypes varied by study. The number of phenotypes identified ranged from 2 to 5. Two phenotypes, with poor longitudinal health outcomes, were common across multiple studies: young patients with severe respiratory disease, few cardiovascular co-morbidities, poor nutritional status and poor health status, and a phenotype of older patients with moderate respiratory disease, obesity, cardiovascular and metabolic co-morbidities.

Conclusions

The recognition that two phenotypes of COPD were often reported may have clinical implications for altering the course of the disease. This review also provided important information on limitations of phenotype studies in COPD and the need for improvement in future studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0208-4) contains supplementary material, which is available to authorized users.     

Cosleeping and sleep problems in children: a systematic review and meta-analysis

Sleep and Biological Rhythms - There exist inconsistent findings about the relation between cosleeping and sleep problems in children. We conducted a meta-analysis to assess these relations and...     

The protective role of coastal marshes: a systematic review and meta-analysis

Background

Salt marshes lie between many human communities and the coast and have been presumed to protect these communities from coastal hazards by providing important ecosystem services. However, previous characterizations of these ecosystem services have typically been based on a small number of historical studies, and the consistency and extent to which marshes provide these services has not been investigated. Here, we review the current evidence for the specific processes of wave attenuation, shoreline stabilization and floodwater attenuation to determine if and under what conditions salt marshes offer these coastal protection services.

Methodology/Principal Findings

We conducted a thorough search and synthesis of the literature with reference to these processes. Seventy-five publications met our selection criteria, and we conducted meta-analyses for publications with sufficient data available for quantitative analysis. We found that combined across all studies (n = 7), salt marsh vegetation had a significant positive effect on wave attenuation as measured by reductions in wave height per unit distance across marsh vegetation. Salt marsh vegetation also had a significant positive effect on shoreline stabilization as measured by accretion, lateral erosion reduction, and marsh surface elevation change (n = 30). Salt marsh characteristics that were positively correlated to both wave attenuation and shoreline stabilization were vegetation density, biomass production, and marsh size. Although we could not find studies quantitatively evaluating floodwater attenuation within salt marshes, there are several studies noting the negative effects of wetland alteration on water quantity regulation within coastal areas.

Conclusions/Significance

Our results show that salt marshes have value for coastal hazard mitigation and climate change adaptation. Because we do not yet fully understand the magnitude of this value, we propose that decision makers employ natural systems to maximize the benefits and ecosystem services provided by salt marshes and exercise caution when making decisions that erode these services.     

Soil-transmitted helminth reinfection after drug treatment: a systematic review and meta-analysis

Background

Soil-transmitted helminth (STH) infections (i.e., Ascaris lumbricoides, hookworm, and Trichuris trichiura) affect more than a billion people. Preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations), is the mainstay of control. This strategy, however, does not prevent reinfection. We performed a systematic review and meta-analysis to assess patterns and dynamics of STH reinfection after drug treatment.

Methodology

We systematically searched PubMed, ISI Web of Science, EMBASE, Cochrane Database of Systematic Reviews, China National Knowledge Infrastructure, WanFang Database, Chinese Scientific Journal Database, and Google Scholar. Information on study year, country, sample size, age of participants, diagnostic method, drug administration strategy, prevalence and intensity of infection pre- and posttreatment, cure and egg reduction rate, evaluation period posttreatment, and adherence was extracted. Pooled risk ratios from random-effects models were used to assess the risk of STH reinfection after treatment. Our protocol is available on PROSPERO, registration number: CRD42011001678.

Principal Findings

From 154 studies identified, 51 were included and 24 provided STH infection rates pre- and posttreatment, whereas 42 reported determinants of predisposition to reinfection. At 3, 6, and 12 months posttreatment, A. lumbricoides prevalence reached 26% (95% confidence interval (CI): 16–43%), 68% (95% CI: 60–76%) and 94% (95% CI: 88–100%) of pretreatment levels, respectively. For T. trichiura, respective reinfection prevalence were 36% (95% CI: 28–47%), 67% (95% CI: 42–100%), and 82% (95% CI: 62–100%), and for hookworm, 30% (95% CI: 26–34%), 55% (95% CI: 34–87%), and 57% (95% CI: 49–67%). Prevalence and intensity of reinfection were positively correlated with pretreatment infection status.

Conclusion

STH reinfections occur rapidly after treatment, particularly for A. lumbricoides and T. trichiura. Hence, there is a need for frequent anthelmintic drug administrations to maximize the benefit of preventive chemotherapy. Integrated control approaches emphasizing health education and environmental sanitation are needed to interrupt transmission of STH.     

Recipient outcomes after ABO-incompatible liver transplantation: a systematic review and meta-analysis

Background

ABO-incompatible live transplantation (ILT) is not occasionally performed due to a relative high risk of graft failure. Knowledge of both graft and patient survival rate after ILT is essential for donor selection and therapeutic strategy. We systematically reviewed studies containing outcomes after ILT compared to that after ABO-compatible liver transplantation (CLT).

Methodology/Principal Findings

We carried out a comprehensive search strategy on MEDLINE (1966–July 2010), EMBASE (1980–July 2010), Biosis Preview (1969–July 2010), Science Citation Index (1981–July 2010), Cochrane Database of Systematic Reviews (Cochrane Library, issue 7, 2010) and the National Institute of Health (July 2010). Two reviewers independently assessed the quality of each study and abstracted outcome data. Fourteen eligible studies were included which came from various medical centers all over the world. Meta-analysis results showed that no significantly statistical difference was found in pediatric graft survival rate, pediatric and adult patient survival rate between ILT and CLT group. In adult subgroup, the graft survival rate after ILT was significantly lower than that after CLT. The value of totally pooled OR was 0.64 (0.55, 0.74), 0.92 (0.62, 1.38) for graft survival rate and patient survival rate respectively. The whole complication incidence (including acute rejection and biliary complication) after ILT was higher than that after CLT, as the value of totally pooled OR was 3.02 (1.33, 6.85). Similarly, in acute rejection subgroup, the value of OR was 2.02 (1.01, 4.02). However, it was 4.08 (0.90, 18.51) in biliary complication subgroup.

Conclusions/Significance

In our view, pediatric ILT has not been a contraindication anymore due to a similar graft and patient survival rate between ILT and CLT group. Though adult graft survival rate is not so satisfactory, ILT is undoubtedly life-saving under exigent condition. Most studies included in our analysis are observational researches. Larger scale of researches and Randomized-Control Studies are still needed.     

The relationship between proteinuria and coronary risk: a systematic review and meta-analysis

Background

Markers of kidney dysfunction such as proteinuria or albuminuria have been reported to be associated with coronary heart disease, but the consistency and strength of any such relationship has not been clearly defined. This lack of clarity has led to great uncertainty as to how proteinuria should be treated in the assessment and management of cardiovascular risk. We therefore undertook a systematic review of published cohort studies aiming to provide a reliable estimate of the strength of association between proteinuria and coronary heart disease.

Methods and Findings

A meta-analysis of cohort studies was conducted to obtain a summary estimate of the association between measures of proteinuria and coronary risk. MEDLINE and EMBASE were searched for studies reporting an age- or multivariate-adjusted estimate and standard error of the association between proteinuria and coronary heart disease. Studies were excluded if the majority of the study population had known glomerular disease or were the recipients of renal transplants. Two independent researchers extracted the estimates of association between proteinuria (total urinary protein >300 mg/d), microalbuminuria (urinary albumin 30–300 mg/d), macroalbuminuria (urinary albumin >300 mg/d), and risk of coronary disease from individual studies. These estimates were combined using a random-effects model. Sensitivity analyses were conducted to examine possible sources of heterogeneity in effect size. A total of 26 cohort studies were identified involving 169,949 individuals and 7,117 coronary events (27% fatal). The presence of proteinuria was associated with an approximate 50% increase in coronary risk (risk ratio 1.47, 95% confidence interval [CI] 1.23–1.74) after adjustment for known risk factors. For albuminuria, there was evidence of a dose–response relationship: individuals with microalbuminuria were at 50% greater risk of coronary heart disease (risk ratio 1.47, 95% CI 1.30–1.66) than those without; in those with macroalbuminuria the risk was more than doubled (risk ratio 2.17, 1.87–2.52). Sensitivity analysis indicated no important differences in prespecified subgroups.

Conclusion

These data confirm a strong and continuous association between proteinuria and subsequent risk of coronary heart disease, and suggest that proteinuria should be incorporated into the assessment of an individual''s cardiovascular risk.     

Multidimensional prognostic indices for use in COPD patient care. A systematic review

Background

A growing number of prognostic indices for chronic obstructive pulmonary disease (COPD) is developed for clinical use. Our aim is to identify, summarize and compare all published prognostic COPD indices, and to discuss their performance, usefulness and implementation in daily practice.

Methods

We performed a systematic literature search in both Pubmed and Embase up to September 2010. Selection criteria included primary publications of indices developed for stable COPD patients, that predict future outcome by a multidimensional scoring system, developed for and validated with COPD patients only. Two reviewers independently assessed the index quality using a structured screening form for systematically scoring prognostic studies.

Results

Of 7,028 articles screened, 13 studies comprising 15 indices were included. Only 1 index had been explored for its application in daily practice. We observed 21 different predictors and 7 prognostic outcomes, the latter reflecting mortality, hospitalization and exacerbation. Consistent strong predictors were FEV₁ percentage predicted, age and dyspnoea. The quality of the studies underlying the indices varied between fairly poor and good. Statistical methods to assess the predictive abilities of the indices were heterogenic. They generally revealed moderate to good discrimination, when measured. Limitations: We focused on prognostic indices for stable disease only and, inevitably, quality judgment was prone to subjectivity.

Conclusions

We identified 15 prognostic COPD indices. Although the prognostic performance of some of the indices has been validated, they all lack sufficient evidence for implementation. Whether or not the use of prognostic indices improves COPD disease management or patients'' health is currently unknown; impact studies are required to establish this.     

Previous lung diseases and lung cancer risk: a systematic review and meta-analysis

Background

In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.

Methods

Relevant studies were identified through MEDLINE searches. Using random effects models, summary effects of specific previous conditions were evaluated separately and combined. Stratified analyses were conducted based on smoking status, gender, control sources and continent.

Results

A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies). The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22–1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI = 1.49, 2.08), (from 30 studies). Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR = 1.22, 0.97–1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).

Conclusions

Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer.     

Association of HLA and post-schistosomal hepatic disorder: a systematic review and meta-analysis

Several human genetic variants, HLA antigens and alleles are reportedly linked to post-schistosomal hepatic disorder (PSHD), but the results from these reports are highly inconclusive. In order to estimate overall associations between human genetic variants, HLA antigens, HLA alleles and PSHD, we systematically reviewed and performed a meta-analysis of relevant studies in both post-schistosomal hepatic disorder and post-schistosomal non-hepatic disorder patients. PubMed, Scopus, Google Scholar, The HuGE Published Literature database, Cochrane Library, and manual search of reference lists of articles published before July 2009 were used to retrieve relevant studies. Two reviewers independently selected articles and extracted data on study characteristics and data regarding the association between genetic variants, HLA antigens, HLA alleles and PSHD in the form of 2×2 tables. A meta-analysis using fixed-effects or random-effects models to pooled odds ratios (OR) with corresponding 95% confidence intervals were calculated only if more than one study had investigated particular variation. We found 17 articles that met our eligibility criteria. Schistosoma mansoni and Schistosoma japonicum were reported as the species causing PSHD. Since human genetic variants were only investigated in one study, these markers were not assessed by meta-analysis. Thus, only HLA-genes (a total of 66 HLA markers) were conducted in the meta-analysis. Our meta-analysis showed that human leucocyte antigens HLA-DQB1*0201 (OR=2.64, P=0.018), DQB1*0303 (OR=1.93, P=0.008), and DRB1*0901 (OR=2.14, P=0.002) alleles and HLA-A1 (OR=5.10, P=0.001), A2 (OR=2.17, P=0.005), B5 (OR=4.63, P=0.001), B8 (OR=2.99, P=0.02), and B12 (OR=5.49, P=0.005) serotypes enhanced susceptibility to PSHD, whereas HLA-DQA1*0501 (OR=0.29, P≤0.001) and DQB1*0301 (OR=0.58, P=0.007) were protective factors against the disease. We further suggested that the DRB1*0901-DQB1*0201, DRB1*0901-DQB1*0303 and A1-B8 haplotypes enhanced susceptibility to PSHD, whereas DQA1*0501-DQB1*0301 linkage decreased the risk of PSHD. The result improved our understanding of the association between the HLA loci and PSHD with regard to pathogenic or protective T-cells and provided novel evidence that HLA alleles may influence disease severity.