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[Critical appraisal of a meta-analysis on the effects of hormone replacement therapy on non-vertebral fractures and suggestions to increase the transparency of meta-analyses].

The present article discusses the difficulties in using data from a meta-analysis of the effects of hormone replacement therapy on non-vertebral fractures. Comparison between the fracture data extracted from the primary studies and the data included in the meta-analysis showed discrepancies for the primary endpoint in three out of 14 studies. Since the complex decision processes behind meta-analyses are often not transparent to the reader it is recommended to provide further details on decision processes for data collection, selection and inclusion criteria for unpublished data. This information could be made available on the website of the publishing journal.

Aged↗

Global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD: a systematic review and meta-analysis.

BACKGROUND: The presence of diabetes increases the risk of adverse outcomes of patients with non-alcoholic fatty liver disease (NAFLD) even in those with lean or non-obese NAFLD. However, the epidemiological data regarding the prevalence of diabetes and prediabetes in lean or non-obese NAFLD populations remain limited. We assessed the global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD. METHODS: Published studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science databases from the inception of the databases to October 2024. The pooled global prevalence of diabetes or prediabetes in patients with NAFLD was evaluated using random-effects meta-analysis. Subgroup meta-analysis and meta-regression were used to investigate potential sources of heterogeneity. RESULTS: A total of 54 studies involving 146,714 patients with non-obese or lean NAFLD were included. The pooled global prevalence of diabetes among patients with lean or non-obese NAFLD was 15.6% (95% CI 10.8%-22.7%). Studies from South America reported the highest prevalence (41.3%, CI 39.1%-43.5%). Meta-regression models showed that geographic region and mean age (p&#x2009;<&#x2009;0.05) were associated with the were associated with the prevalence of diabetes, jointly accounting for 51.61% of the heterogeneity. The global prevalence of prediabetes among patients with lean or non-obese NAFLD was 22.9% (95% CI 12.5%-41.9%) with the highest prevalence reported in studies from Europe (34.4%, CI 23.0%-51.4%). Meta-regression models showed that geographic region and country (p&#x2009;<&#x2009;0.05) were associated with the prevalence of prediabetes, jointly accounting for 73.65% of the heterogeneity. CONCLUSION: The pooled global prevalence of diabetes and prediabetes were 15.6% and 22.9% in lean or non-obese patients with NAFLD, respectively. These findings suggest the importance of diabetes screening in these patients.

Humans↗

Extracorporeal shock wave therapy for Peyronie's disease: exploratory meta-analysis of clinical trials.

PURPOSE: Extracorporeal shock wave therapy (ESWT) for the treatment of Peyronie's disease is still controversial. This exploratory meta-analysis of published studies in the international literature investigates its therapeutic effects. MATERIALS AND METHODS: The treatment outcomes from 17 study groups identified by a computerized literature search were compared with natural history outcomes and data from control groups from 2 controlled ESWT studies. An exploratory meta-analysis was performed because a methodologically sound meta-analysis lege artis did not appear appropriate, since treated groups differ considerably in structure, the selection of outcome measures is inconsistent and measurement is not standardized. RESULTS: ESWT seems to have an effect on penile pain during erection and on the improvement of sexual function. Pain seems to resolve faster after ESWT than during the course of the natural history. The effect on plaque size and penile curvature is less impressive. CONCLUSIONS: ESWT in Peyronie's disease at least seems to be effective in regard to penile pain and sexual function compared to natural history. Deducing from these data the effect on plaque size and curvature remains questionable. However, ESWT is not an evidence based therapy at present. A controlled (preferably pairwise matched), single blind, multicenter study with careful, detailed documentation of disease symptoms before intervention and of outcomes is required to evaluate the real effect of ESWT.

Clinical Trials as Topic↗

Controversy of oral contraceptives and risk of rheumatoid arthritis: meta-analysis of conflicting studies and review of conflicting meta-analyses with special emphasis on analysis of heterogeneity.

The authors analyze the heterogeneity present in the combined results of past observational studies that investigated the association between oral contraceptive use and rheumatoid arthritis. The authors also evaluate discrepancies among meta-analyses that focus on the same relation. Of the 15 initially reviewed studies, 10 were selected for this meta-analysis, which also includes a qualitative summary of study characteristics and a critical appraisal of study quality. The authors used the direct method to combine the study results when there was no evidence of heterogeneity and the DerSimonian-Laird method when heterogeneity was present. Using a meta-regression to assess the sources of heterogeneity, the authors weighted summary estimates by sample size and undertook a sensitivity analysis. There was a strong indication of heterogeneity when combining all studies (x2 = 29.34, p = 0.00060) with the source of controls explaining most of the heterogeneity. The most important factor in explaining the differences among the overall summary estimates given by the meta-analyses is that different effect estimates had been selected for the same studies. There is no conclusive evidence of a protective effect of oral contraceptives on the risk of developing rheumatoid arthritis. Consensus is needed on how meta-analyses of observational studies should be conducted.

Arthritis, Rheumatoid↗

Meta-analysis of polytetrafluoroethylene bypass grafts to infrapopliteal arteries.

CONTEXT: Reports of polytetrafluoroethylene (PTFE) bypass grafting to the infrapopliteal arteries have often used survival analysis of acceptable quality to describe a wide range of long-term results. In theory, these results may be combined if variability between series and time intervals is considered. OBJECTIVE: Meta-analysis was performed to gain insight into long-term graft patency and foot preservation after PTFE bypass grafting to infrapopliteal arteries. DATA SOURCE: Studies published from 1982 through 2001 were identified from the PubMed database and pertinent original articles. STUDY SELECTION: Three investigators selected 43 studies that used survival analysis, reported 2-year patency rates, and included at least 15 bypass procedures. Data extraction and transformation: Based on standard life-tables or survivor curves, an interval success rate was calculated for each month in each series. The monthly success rates were combined across series, enabling construction of pooled survivor curves. DATA SYNTHESIS: Random-effects meta-analysis yielded 5-year pooled estimates (SE) of 30.5% (7.6%) for primary graft patency, 39.7% (5.5%) for secondary graft patency, and 55.7% (5.0%) for foot preservation. During the entire follow-up, pooled estimates were slightly higher for series of PTFE grafts with adjunctive procedures compared with series of PTFE grafts only. Sensitivity analysis: A simulation using only unfavorable assumptions showed a decrease of less than 5% at 5 years for all outcomes, and smaller differences at subgroup meta-analysis. Funnel plots suggested that publication bias was unlikely. CONCLUSION: This meta-analysis indicated moderate success for PTFE bypass grafts to infrapopliteal arteries, but the role of adjunctive procedures at the distal anastomosis remains uncertain.

Arterial Occlusive Diseases↗

Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials.

OBJECTIVE: To conduct a meta-analysis of 11 randomized controlled trials comparing enteral nutritional support supplemented with key nutrients versus standard enteral nutritional support to determine effects on morbidity and mortality rates and hospital stay. BACKGROUND DATA: Recent studies have shown that malnutrition occurs in up to 30% of patients undergoing gastrointestinal surgery, resulting in an increased risk of postoperative complications and death. With the realization that key nutrients can modulate inflammatory, metabolic, and immune processes, enteral nutritional regimens (supplemented with large amounts of key nutrients) have been developed for clinical use. METHODS: Eleven prospective, randomized controlled trials evaluating 1009 patients treated with combinations of key nutrients (Impact, Immun-Aid) were evaluated. Outcome measures examined were the incidences of pneumonia, infectious complications, and death, and length of hospital stay. Meta-analyses were undertaken to obtain the odds ratio and 95% confidence interval for incidences of infectious complications, pneumonia, and death, and the weighted mean difference and 95% confidence interval for length of hospital stay. RESULTS: The provision of nutritional support supplemented with key nutrients to patients with critical illness resulted in a decrease in infectious complications when compared with patients receiving standard nutritional support and a significant reduction in overall hospital stay. Similar results were documented in patients with gastrointestinal cancer. However, there were no differences between patient groups for either pneumonia or death. CONCLUSIONS: This meta-analysis has demonstrated that nutritional support supplemented with key nutrients results in a significant reduction in the risk of developing infectious complications and reduces the overall hospital stay in patients with critical illness and in patients with gastrointestinal cancer. However, there is no effect on death. These data have important implications for the management of such patients.

Abdominal Abscess↗

An updated meta-analysis of calcium-channel blockers in the prevention of restenosis after coronary angioplasty.

BACKGROUND: In 1994, a meta-analysis of 5 small randomized trials reported a 30% reduction in the odds of angiographic restenosis when calcium-channel blockers (CCB) were given after percutaneous coronary intervention. Recently, the results of 2 large similar trials (Nisoldipine In Coronary Artery Disease in Leuven [NICOLE], and Coronary AngioPlasty Amlodipine in REstenosis Study [CAPARES]) were published. An extended meta-analysis including the results of the latter trials was performed. METHODS: A total of 2380 patients were analyzed. Statistical analysis included calculation of odds ratios for each trial, common odds ratio, and homogeneity for treatment effects across trials. RESULTS: The incidence of angiographic restenosis was 36% in the CCB-treated group and 42% in the placebo group. The odds ratio of restenosis with CCB therapy was 0.78 (95% CI 0.64-0.95) compared with control patients (P =.01). Treatment effects were homogeneous across the trials. For the combined end point of death, coronary artery bypass grafting, repeat percutaneous transluminal coronary angioplasty, and myocardial infarction, 126 of 626 events occurred in the CCB group and 191 of 655 in the placebo group (odds ratio 0.61 [95% CI 0.47-0.80], P <.001). CONCLUSIONS: This extended meta-analysis confirmed a reduction in the odds of restenosis and clinical events when CCBs were added to standard therapy after percutaneous coronary intervention.

Amlodipine↗

Borrowing strength from external trials in a meta-analysis.

There exists a variety of situations in which a random effects meta-analysis might be undertaken using a small number of clinical trials. A problem associated with small meta-analyses is estimating the heterogeneity between trials. To overcome this problem, information from other related studies may be incorporated into the meta-analysis. A Bayesian approach to this problem is presented using data from previous meta-analyses in the same therapeutic area to formulate a prior distribution for the heterogeneity. The treatment difference parameters are given non-informative priors. Further, related trials which compare one or other of the treatments of interest with a common third treatment are included in the model to improve inference on both the heterogeneity and the treatment difference. Two approaches to estimating relative efficacy are considered, namely a general parametric approach and a method explicit to binary data. The methodology is illustrated using data from 26 clinical trials which investigate the prevention of cirrhosis using beta-blockers and sclerotherapy. Both sources of external information lead to more precise posterior distributions for all parameters, in particular that representing heterogeneity.

Adrenergic beta-Antagonists↗

A meta-analysis of trials of transurethral needle ablation for treating symptomatic benign prostatic hyperplasia.

OBJECTIVES: To investigate the short- and long-term effectiveness of transurethral needle ablation (TUNA) of the prostate for clinical benign prostatic hyperplasia (BPH), using a meta-analysis of all clinical studies involving TUNA. METHODS: Data were extracted from two randomized trials, two non-randomized observational protocols and 10 single-arm studies conducted on TUNA, according to a determined protocol. The meta-analysis was based on the change in the mean score at the end of study from that at baseline. The estimation of the effects from the meta-analysis used a multilevel model including random effects for the studies. RESULTS: In all studies the patients recruited had severe lower urinary tract symptoms and a mean International Prostate Symptom Score (IPSS) of > 20 before treatment. The effect of TUNA was to halve the mean IPSS at 1 year after treatment and, although there was a slight tendency for the IPSS to increase in all arms from year 1 to year 5, this decrease by half was maintained at 5 years. The maximum urinary flow rate (Q(max)) also increased by approximately 70% from baseline to 1 year and in virtually all studies the mean Q(max) approached or exceeded 15 mL/s. Although there was a tendency for Q(max) to decline slightly over time, the mean Q(max) 5 years after treatment was > 50% over baseline. CONCLUSIONS: This meta-analysis shows that TUNA is an effective and minimally invasive treatment for men with clinical BPH, even when the symptoms are severe. There is a significant improvement in symptoms and flow rate after 1 year which persists for at least 5 years. TUNA therapy would appear to be an alternative to surgery and an attractive option for men who do not wish to undergo long-term medical therapy, are poor candidates for surgery or are concerned about the side-effects of TURP.

Aged↗

Transcutaneous vagus nerve stimulation influences sleep quality and insomnia: A systematic review and meta-analysis.

Impairments in sleep quality, timing, or duration disrupt normal sleep patterns. This systematic review and meta-analysis investigated the effects of transcutaneous vagus nerve stimulation (tVNS) protocols on sleep outcomes. Thirteen randomized controlled trials with parallel or crossover designs that applied tVNS intervention and assessed sleep quality (Pittsburgh Sleep Quality Index) and insomnia severity (Athens Insomnia Scale and Insomnia Severity Index) were included. Effect sizes were calculated by comparing changes between the active tVNS and control groups. Moderator analyses examined whether stimulation of different targeted regions influences sleep outcomes. Meta-regression analyses examined potential relationships between the effects of tVNS protocols on sleep quality and demographic characteristics and multiple tVNS parameters, respectively. The random-effects meta-analysis indicated that tVNS protocols influenced better sleep quality and lower insomnia severity. Moderator variable analysis revealed that tVNS targeting the concha region induced better sleep quality. Meta-regression analysis revealed that better sleep quality was associated with lower ages of participants. These findings suggest that tVNS protocols, particularly those targeting the concha, were associated with favorable changes in sleep quality and insomnia severity, with age potentially moderating the treatment response.

Humans↗

Meta-analysis of the functional neuroanatomy of single-word reading: method and validation.

Intersubject variability and subtle differences in experimental design can lead to variable results in studies of cognitive processes such as reading. To accurately identify the neural processes associated with cognition and sensorimotor processing, meta-analytic methods capable of identifying areas of consistent activation among studies are useful. This paper describes a novel approach for combining published neuroimaging results from multiple studies, designed to maximize the quantification of interstudy concordance while minimizing the subjective aspects of meta-analysis. In this method, a localization probability distribution was modeled for each activation focus obtained from 11 PET studies of reading single words aloud, and the union of these distributions was taken to yield an activation likelihood estimate map for the brain. Significance was assessed via permutation analysis of randomly generated sets of foci. Regions of significant concordance were identified in bilateral motor and superior temporal cortices, pre-SMA, left fusiform gyrus, and the cerebellum. These meta-analytic results were validated by comparison with new fMRI data on aloud word reading in normal adult subjects. Excellent correspondence between the two statistical maps was observed, with fMRI maxima lying close to all meta-analysis peaks and statistical values at the peaks identified by the two techniques correlating strongly. This close correspondence between PET meta-analysis and fMRI results also demonstrates the validity of using fMRI for the study of language tasks involving overt speech responses. Advantages of this automated meta-analysis technique include quantification of the level of concordance at all brain locations and the provision for use of a threshold for statistical significance of concordance.

Brain↗

Neural networks in frontotemporal dementia--a meta-analysis.

OBJECTIVE: Frontotemporal dementia is the most common form of frontotemporal lobar degeneration. It is characterized by deep alterations in behavior and personality. We conducted a systematic and quantitative meta-analysis to examine its neural correlates and place the disease in a framework of cognitive neuropsychiatry. METHODS: MedLine and Current Contents search engines were used to identify imaging studies investigating frontotemporal dementia between 1980 and 2005. Nine studies were identified reporting either atrophy or decreases in glucose utilization. Finally, the analysis involved 132 patients and 166 controls. A quantitative meta-analysis was performed. Maxima of the studies resulted in activation likelihood estimates. RESULTS: The meta-analysis revealed a particularly frontomedian network impaired in frontotemporal dementia. Additionally, right anterior insula, and medial thalamus were identified. CONCLUSIONS: Our study specifies frontotemporal dementia as the frontomedian variant of frontotemporal lobar degeneration. The disease affects neural networks enabling self-monitoring, theory of mind capabilities, processing/evaluation of internal mental states, perception of pain and emotions, and sustaining personality and self. Our study contributes to placing frontotemporal dementia in cognitive neuropsychiatry.

Aged↗

A meta-analysis of 25 hydroxyvitamin D in older people with fracture of the proximal femur.

AIMS: To perform a meta-analysis on the published studies of serum levels of 25 hydroxyvitamin D in older people with fractures of the proximal femur compared to control groups. METHODS: A 'Medline' literature search using key words vitamin D' and 'hip fractures' for the years January 1966 to June 1999, seeking only papers published in English and available from New Zealand medical libraries, was performed. Bibliographies of identified papers were also searched. Studies which compared 25 hydroxyvitamin D levels in people with a fracture of the proximal femur to an older control group were eligible for inclusion. 30 studies were identified and 28 papers could be found in New Zealand. The method of weighted Z statistics was used in the meta-analysis. RESULTS: The pooled reduction in serum 25 hydroxyvitamin D for the fracture group compared to the controls was 0.66 of a standard deviation with a 95% confidence interval of 0.74 to 0.59. CONCLUSIONS: Although there may be publication bias in this meta-analysis and there was some evidence of heterogeneity in the studies, there is very good evidence that older people with fracture of the proximal femur have reduced levels of vitamin D compared to controls. Older people with fracture of the proximal femur should be treated with vitamin D.

Age Factors↗

Adolescent drinking behaviour and family socialization factors: a meta-analysis.

Family socialization processes are important influences on behaviour in childhood and adolescence. Two major dimensions of family socialization are Support and Control, and these two dimensions were assessed for their influence on adolescent drinking behaviour. Thirty recently published research studies, which reported the influence of (clearly identifiable) family socialization variables on (self-reported) adolescent drinking behaviour were selected for analysis. The results of these studies were subjected to meta-analysis using a sorting technique. Variables were sorted along the dimensions of Support and Control, and along a Family Structure dimension, which measured parental intactness. Results of the meta-analysis indicated a clear negative linear relationship between Support and adolescent drinking. There was also a negative linear relationship between Control and drinking behaviour. Thus low support and lax control were associated with increased drinking. However, there was some evidence of a possible curvilinear relationship between control and adolescent drinking. A negative relationship between Family Structure and adolescent drinking was also found, i.e. adolescents from non-intact families tend to drink more. The results were incorporated into a family systems perspective. It is suggested that extremes of Support and Control, when measured adequately, may be dysfunctional for adequate socialization into normal drinking behaviour, as defined by social and cultural norms, during adolescence.

Adolescent↗

Meta-analysis of the influence of MDR1 C3435T polymorphism on digoxin pharmacokinetics and MDR1 gene expression.

AIMS: Studies revealing conflicting results of the functional significance of MDR1 exon 26 C3435T SNP on the disposition of digoxin in different ethnic groups led us to perform a meta-analysis on published data investigating the influence of C3435T SNP on the pharmacokinetics of digoxin and the expression of MDR1. METHODS: Meta-analysis was performed on data from published studies investigating the influence of MDR1 C3435T SNP on digoxin pharmacokinetics, as well as MDR1 expression in Caucasian and Japanese populations. The following outcomes were included: exposures to digoxin measured by area under the concentration-time curve and maximum concentration, the mean intestinal MDR1 mRNA expression and P-gp expression in the absence of digoxin administration. RESULTS: The overall results of the meta-analysis in Caucasian and Japanese subjects suggested no major influence of the C3435T SNP on exposure levels of digoxin as determined by AUC(0-4 h) or AUC(0-24 h) although C(max) values for digoxin were lower in wild-type (CC) subjects compared with subjects harbouring TT genotypes. Subgroup analysis by ethnic populations showed the oral availability of digoxin to be lower in wild-type Caucasian populations compared with wild-type Japanese subjects. No causal relationships were detected between the C3435T SNP and MDR1 mRNA or protein expression. CONCLUSIONS: Our meta-analysis of available studies indicates that the synonymous MDR1 C3435T SNP does not affect the pharmacokinetics of digoxin and the expression of MDR1 mRNA. Future studies should focus on the impact of MDR1 haplotypes on the pharmacokinetics of MDR1 substrates rather than the C3435T SNP alone.

Administration, Oral↗

N-acetylcysteine and contrast-induced nephropathy: a meta-analysis of 13 randomized trials.

BACKGROUND: Contrast-induced nephropathy (CIN) following coronary angiography increases morbidity and mortality. Randomized trials of small sample size have evaluated whether N-acetylcysteine (NAC) prevents CIN in patients with renal dysfunction. METHODS: To conduct a meta-analysis of the randomized trials the following databases were searched: MEDLINE (1966-2003), Cochrane Controlled Trials Register, ACP Journal Club online, published abstracts presented at the major cardiology and nephrology meetings, references from reviews. Two authors independently evaluated all relevant randomized trials. Eligibility criteria were (1) randomized placebo controlled trials of NAC, (2) patients with impaired renal function (creatinine >1.2 mg/dL) undergoing coronary angiography, (3) patients receiving intravenous fluids and low-osmolarity nonionic contrast media, (4) the primary outcome was CIN (increases in creatinine of either at least 0.5 mg/dL or 25% from baseline to 48 hours). Of 589 trials reviewed 3 disagreements were easily resolved by mutual discussion and 13 were selected. Data extraction included patient characteristics, intravenous fluid regimen, type and dose of contrast media, dosing regimen, creatinine at baseline and 48 hours and CIN requiring dialysis. RESULTS: Four of the 13 trials reported statistically significant results. In meta-analysis of the 13 trials, which included 1892 patients, the RR was 0.68 (95%CI, 0.46-1.01). The addition of the trial of patients undergoing computerized tomography, which had formulated the hypothesis, yielded a statistically significant reduction (RR 0.64 [95%CI 0.42-0.96]) as did an earlier meta-analysis of 7 trials. CONCLUSIONS: Our meta-analysis of the most currently available randomized data concerning NAC before coronary angiography to prevent CIN in patients with impaired renal function is neither conclusive nor provides proof beyond a reasonable doubt to influence clinical practice and public policy. The intervention has minimal toxicity but the width of the 95% CI remains compatible with a range from a large benefit to none at all. In addition, the trials used change in creatinine as the measure of outcome. Further randomized trials of large sample size and with clinical outcomes will add importantly relevant information to the totality of evidence and allow the most rational clinical decisions for individual patients as well as policy decisions for the health of the general public.

Acetylcysteine↗

Role of adjuvant chemotherapy in patients with resected non-small-cell lung cancer: reappraisal with a meta-analysis of randomized controlled trials.

PURPOSE: The role of adjuvant chemotherapy in patients with resected non-small-cell lung cancer (NSCLC) remains to be defined. This study was aimed at re-evaluating the effectiveness of adjuvant chemotherapy in patients with resected NSCLC, by performing a meta-analysis of relevant trials. METHODS: We performed a literature search to identify trials reported after the publication of a meta-analysis in 1995, comparing patients with NSCLC receiving chemotherapy after surgery with those undergoing surgery alone. The hazard ratio (HR) was estimated to assess the survival advantage of adjuvant chemotherapy. RESULTS: Eleven trials conducted on a total of 5,716 patients were identified by the literature search. In these trials, hazard ratio estimates suggested that adjuvant chemotherapy yielded a survival advantage over surgery alone (HR, 0.872; 95% CI, 0.805 to 0.944; P =.001). In a subset analysis, both cisplatin-based chemotherapy (HR, 0.891; 95% CI, 0.815 to 0.975; P =.012) and single-agent therapy with tegafur and uracil (UFT; HR, 0.799; 95% CI, 0.668 to 0.957; P =.015) were found to yield a significant survival benefit. The toxicities of adjuvant chemotherapy were found to be generally mild. CONCLUSION: This is the first updated meta-analysis demonstrating the importance of cisplatin-based chemotherapy and single-agent UFT therapy as adjuvant chemotherapy in the treatment of resected NSCLC. Although the results must be carefully interpreted because of one limitation (the meta-analysis was performed with abstracted data), they raise critical issues that must be resolved in future studies.

Carcinoma, Non-Small-Cell Lung↗

Meta-analysis of silicosis and lung cancer.

OBJECTIVES: This study examined the association between silicosis and lung cancer in a systematic review (and meta-analysis) of the epidemiologic literature, with special reference to the methodological quality of observational studies. METHODS: We searched Medline, Toxline, BIOSIS and Embase (1966-May 2004) for original articles published in any language and systematically reviewed the bibliographies of the retrieved articles. Observational studies (cohort and case-control studies) were selected if they reported a measure of association [standardized mortality ratio (SMR), relative risk or odds ratio] relating lung cancer to silicosis. RESULTS: Thirty-one studies (27 cohort studies, 4 case-control studies) met the inclusion criteria of the meta-analysis. Without any adjustment for smoking, the meta-analysis of the cohort studies indicated that the common SMR was 2.45 [95% confidence interval (95% CI) 1.63-3.66; homogeneity P<0.0001]. When the results of the cohorts for which mortality data were adjusted for smoking were pooled, the common SMR was 1.60 (95% CI 1.33-1.93; homogeneity P=0.52). In a "dose-response" analysis, the profusion of small and large opacities found in chest X-rays correlated with the risk of death from lung cancer. Overall, the case-control studies were more conservative in their conclusions. CONCLUSIONS: Because of biases inherent to observational studies, it is likely that the risk of lung cancer among silicosis patients is overestimated in the current literature. There is nevertheless evidence, from data restricted to never-smokers and from a "dose-response" analysis, that silicosis and lung cancer are associated.

Bias↗