Random Effects Pooled Odds Ratio Research Articles

Risk factors for suicide in prisons: a systematic review and meta-analysis

SummaryBackgroundRates of suicide among people in prison are elevated compared with people of similar age and sex who are living in the community. Improving assessments and interventions to reduce suicide risk requires updated evidence on risk factors. We aimed to examine risk factors associated with suicide in prisoners.MethodsWe did an updated systematic review and meta-analysis of risk factors for suicide among people in prison. We searched five biblographic databases for articles published between Jan 1, 2006, and Aug 13, 2020, and one database for articles published between Jan 1, 1973, and Aug 13, 2020. Eligible studies reported risk factors in individuals who died by suicide while in prison and in controls from the general prison population. Two reviewers independently extracted data for each study using a standardised form. We calculated random-effects pooled odds ratios (ORs) for the association of suicide with demographical, clinical, criminological, and institutional risk factors, and investigated heterogeneity using subgroup and meta-regression analyses. This systematic review is registered with PROSPERO, CRD42020137979.FindingsWe identified 8041 records through our searches, and used 77 eligible studies from 27 countries, including 35 351 suicides, in the main analysis. The strongest clinical factors associated with suicide were suicidal ideation during the current period in prison (OR 15·2, 95% CI 8·5–27·0), a history of attempted suicide (OR 8·2, 4·4–15·3), and current psychiatric diagnosis (OR 6·4, 3·6–11·1). Institutional factors associated with suicide included occupation of a single cell (OR 6·8, 2·3–19·8) and having no social visits (OR 1·9, 1·5–2·4). Criminological factors included remand status (OR 3·6, 3·1–4·1), serving a life sentence (OR 2·4, 1·3–4·6), and being convicted of a violent offence, in particular homicide (OR 3·1, 2·2–4·2).InterpretationSeveral modifiable risk factors, such as psychiatric diagnosis, suicidal ideation during the current period in prison, and single-cell occupancy, are associated with suicide among people in prison. Preventive interventions should target these risk factors and include improved access to evidence-based mental health care. Understanding other factors associated with suicide might improve risk stratification and resource allocation in prison services.FundingWellcome Trust, National Institute for Health Research Applied Research Collaboration Oxford and Thames Valley.

Dietary and metabolic factors in the pathogenesis of hidradenitis suppurativa: a systematic review.

Hidradenitis suppurativa (HS) is a systemic recalcitrant inflammatory condition characterized by debilitating lesions with high morbidity. Its known association with obesity and smoking indicate correlation with other environmental factors, such as diet, suggesting a larger role for lifestyle modifications in disease treatment. This study seeks to assess the contribution of weight loss and dietary intake in HS management. A primary literature search was conducted using PubMed, Web of Science, and CINAHL in November 2018 to include association and intervention studies on the influence of diet and weight on HS. Twenty-five articles were included. Meta-analysis of nine case-control studies across Asia, Europe, and the United States showed that HS patients are four times more likely to be obese compared to the general population; random effects pooled odds ratio 4.022 (2.667-6.065), P<0.001. Five articles assessed weight-loss interventions and revealed mixed findings. The remaining articles included three association studies on micronutrient levels, eight dietary intervention studies, and one article analyzing both micronutrient association and dietary intervention. Included articles in this systematic review reveal that low serum zinc and vitamin D levels are associated with increased lesion count in HS. Supplementation of zinc, vitamin D, vitamin B12, or exclusion of dairy or brewer's yeast can be effective in partial or complete lesion resolution. Reviewed data show that weight loss from bariatric surgery may lead to HS improvement but often results in more severe malnutrition that worsens or even leads to new onset HS post bariatric surgery. Future reporting is needed to conclusively determine the role of diet in HS.

2819 The Role of Prophylactic Antibiotics in Peritoneal Dialysis Patients Undergoing Colonoscopy: A Systematic Review and Meta-Analysis

INTRODUCTION: End stage renal disease patients on peritoneal dialysis (PD) are at risk of peritonitis due to possible bacterial translocation from the colon during preparation for colonoscopy or during performing colonoscopy. ASGE guidelines and ISPD (International Society for Peritoneal Dialysis) guidelines suggest antibiotic prophylaxis while European Society of Gastroenterology does not give a clear guideline in this regard. ASGE guidelines in this regard is based on weak evidence. We attempted to conduct a systematic literature review and a meta-analysis to provide more evidence in this area. METHODS: A systematic search of PubMed, Medline, Web of Science, and Google Scholar through April 2019 using PRISMA and MOOSE guidelines identified 3 studies that reported on the occurrence of peritonitis during colonoscopy in patients on peritoneal dialysis. Case reports were excluded. Only prospective and retrospective large series studies were included. Random-effects pooled odds ratio and 95% confidence intervals were estimated. Heterogeneity was measured by Cochrane Q and I2 statistics. RESULTS: A total of 3 studies reporting on 216 colonoscopy procedures performed on patients undergoing peritoneal dialysis were included in the final analysis. The mean age ranged from 44 to 64 years. The pooled Odd's ratio of developing peritonitis while on antibiotics during colonoscopy was 0.68 (95% 0.19-2.4, I2 = 0, P = 0.56). This was not statistically significant. No heterogeneity was noted in the analysis. CONCLUSION: Based on our study, the administration of antibiotics does not seem to affect the incidence of peritonitis in PD patients undergoing colonoscopy. However, this is based on very limited number of studies and unequal sample-size in comparison groups. We, therefore, cannot recommend or refute the usage of prophylactic antibiotics in PD patients undergoing colonoscopy. This analysis shows the paucity of data available at this time in this regard. More robust studies with similar comparison groups are warranted to guide decision making.

Risk Factors for Hemorrhagic and Ischemic Stroke in Sub-Saharan Africa.

Introduction In sub-Saharan Africa (SSA), there is a significant burden of ischemic stroke (IS) and hemorrhagic stroke (HS), although data on risk factors for each type are sparse. In this systematic review we attempt to characterize the risk factors. Methods We systematically reviewed (PubMed, EMBASE, WHOLIS, Google Scholar, Wiley online, and the Cochrane Central Register of Controlled Trials (CENTRAL)) case-control studies and case series from 1980 to 2016 that reported risk factors for IS and/or HS in SSA. For each risk factor we calculated random-effects pooled odds ratios (ORs) for case-control studies and pooled prevalence estimates for case series. Results. We identified 12 studies, including 4,387 stroke patients. Pooled analysis showed that patients who had diabetes (OR = 2.39; 95% CI: 1.14–5.03) and HIV (OR = 2.46 (95% CI: 1.59–3.81) were at a significantly greater risk of suffering from all stroke types. There were insufficient data to examine these factors by stroke type. Among case series, the pooled prevalence of hypertension was higher for HS than for IS (73.5% versus 62.8%), while diabetes mellitus (DM) and atrial fibrillation (AF) were more prevalent among IS compared to HS (15.9% versus 10.6% and 9.6% versus 2.3%, respectively). Conclusions There remain too few data from SSA to reliably estimate the effect of various factors on the risk of IS and HS. Furthermore, the vast majority of cases were identified in hospital and so are unlikely to be representative of the totality of stroke cases in the community.

Association between residual teeth number in later life and incidence of dementia: A systematic review and meta-analysis

BackgroundIt has been suggested that tooth loss in later life might increase dementia incidence. The objective of this analysis is to systematically review the current evidence on the relationship between the number of remaining teeth and dementia occurrence in later life.MethodsA search of multiple databases of scientific literature was conducted with relevant parameters for articles published up to March 25th, 2017. Multiple cohort studies that reported the incidence of dementia and residual teeth in later life were found with observation periods ranging from 2.4 to 32 years. Random-effects pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated to examine whether high residual tooth number in later life was associated with a decreased risk of dementia. Heterogeneity was measured by I2. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the overall quality of evidence.ResultsThe literature search initially yielded 419 articles and 11 studies (aged 52 to 75 at study enrollment, n = 28,894) were finally included for analysis. Compared to the low residual teeth number group, the high residual teeth number group was associated with a decreased risk of dementia by approximately 50% (pooled OR = 0.483; 95% CI 0.315 to 0.740; p < 0.001; I2 = 92.421%). The overall quality of evidence, however, was rated as very low.ConclusionDespite limited scientific strength, the current meta-analysis reported that a higher number of residual teeth was associated with having a lower risk of dementia occurrence in later life.

Comparison of the Hospital-Acquired Clostridium difficile Infection Risk of Using Proton Pump Inhibitors versus Histamine-2 Receptor Antagonists for Prophylaxis and Treatment of Stress Ulcers: A Systematic Review and Meta-Analysis.

Background/AimsAlthough proton pump inhibitors (PPIs) have been widely used for the prevention and treatment of stress gastric ulcers in hospital settings, there are concerns that PPIs increase the risk of Clostridium difficile infection (CDI). However, little is known about the risk of CDI following PPI and histamine-2 receptor antagonist (H2RA) use. We evaluated the comparative hospital-acquired CDI occurrence risk associated with the concurrent use of PPIs versus H2RAs.MethodsA systematic search of PubMed, MEDLINE/Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Google Scholar through August 19, 2016, identified 12 studies that reported the hospital-acquired CDI occurrence following H2RA and PPI use for the prevention and treatment of stress gastric ulcers. Random-effects pooled odds ratios and 95% confidence intervals were estimated. Heterogeneity was measured using I2, and a meta-regression analysis was conducted. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the overall quality of the evidence.ResultsA total of 74,132 patients from 12 observational studies were analyzed. Compared to H2RAs, PPIs increased the risk of CDI by 38.6% (pooled odds ratio, 1.386; 95% confidence interval, 1.152 to 1.668; p=0.001; I2=42.81%). Subgroup analyses of the purpose of study medication use, study site, and study design confirmed the consistency of a greater CDI risk with PPIs than with H2RAs. The overall quality of evidence was rated as low.ConclusionsThe use of PPIs for both the prevention and treatment of stress ulcers was associated with a 38.6% increased risk of hospital-acquired CDI occurrence compared to H2RA use.

Effects of hospital palliative care on health, length of stay, and in-hospital mortality across intensive and non-intensive-care units: A systematic review and metaanalysis.

Hospital palliative care has been shown to improve quality of life and optimize hospital utilization for seriously ill patients who need intensive care. The present review examined whether hospital palliative care in intensive care (ICU) and non-ICU settings will influence hospital length of stay and in-hospital mortality. A systematic search of CINAHL/EBSCO, the Cochrane Library, Google Scholar, MEDLINE/Ovid, PubMed, and the Web of Science through 12 October 2016 identified 16 studies that examined the effects of hospital palliative care and reported on hospital length of stay and in-hospital death. Random-effects pooled odds ratios and mean differences with corresponding 95% confidence intervals were estimated. Heterogeneity was measured by the I 2 test. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was utilized to assess the overall quality of the evidence. Of the reviewed 932 articles found in our search, we reviewed the full text of 76 eligible articles and excluded 60 of those, which resulted in a final total of 16 studies for analysis. Five studies were duplicated with regard to outcomes. A total of 18,330 and 9,452 patients were analyzed for hospital length of stay and in-hospital mortality from 11 and 10 studies, respectively. Hospital palliative care increased mean hospital length of stay by 0.19 days (pooled mean difference = 0.19; 95% confidence interval [CI 95%] = -2.22-2.61 days; p = 0.87; I 2 = 95.88%) and reduced in-hospital mortality by 34% (pooled odds ratio = 0.66; CI 95% = 0.52-0.84; p < 0.01; I 2 = 48.82%). The overall quality of evidence for both hospital length of stay and in-hospital mortality was rated as very low and low, respectively. Hospital palliative care was associated with a 34% reduction of in-hospital mortality but had no correlation with hospital length of stay.

Suicide in prisoners with bipolar disorder and other psychiatric disorders: a systematic review

To examine the risk of suicide and suicide attempts in prisoners with bipolar disorder and other psychiatric disorders compared with prisoners without psychiatric disorders. We conducted a systematic review and meta-analysis of observational studies comparing suicide outcomes in prisoners with bipolar disorder and other psychiatric disorders to other prisoners. Five studies reported the risk of suicidal outcomes in prisoners with bipolar disorder compared with other prisoners, with a random effects pooled odds ratio of 2.4 (95% confidence interval: 1.6-3.7; I(2) = 0%). This appeared to be lower than the risk of suicidal outcomes for all psychiatric disorders and for depression, specifically, and, in meta-regression, significantly lower (p = 0.03) than for schizophrenia-spectrum disorders. Although bipolar disorder is associated with suicide and non-fatal suicidal behavior in prisoners, further research is necessary to confirm any associations and mediating mechanisms.

Abstract WMP90: Homozygous Short Variation Allele Genotype of the Serotonin-Transporter-Linked Polymporphic Region (5-HTTLPR) is Associated Post-Sstroke Depression- A Meta-analysis

Aim: Polymorphisms of the genes for encoding serotonin transporter, specifically, the length variation in the serotonin-transporter-linked polymorphic region (5-HTTLPR), a single nucleotide polymorphisms, in the 5-HTTLPR (RS25531), and variable number of tandem repeats (VNTR) in the second intron 2 (STin2) have been implicated in the development of post-stroke depression (PSD). We aimed at evaluating this association in the published literature. Methods: Random-effects meta-analyses were conducted among studies examining the relations between the polymorphisms of the genes encoding serotonin transporter and the risk of developing PSD. Meta-regression identified patient- and study-related factors that may contribute to heterogeneity. Results: Five studies consisting of patients suffering from PSD and stroke patients without PSD were included. Our analyses showed statistically significant evidence of the positive association between the homozygous short (S) variation allele genotype of the 5-HTTLPR (SS) and PSD (random-effects pooled odds ratio (OR) = 2.05, 95% Confidence Interval (CI) = 1.41-2.98, Z =3.79, p&lt; 0.001 ). Our analyses also showed significant evidence of a negative association between the homozygous long (L) variation alleles of the 5-HTTLPR (LL) and PSD (random-effects OR = 0.52, 95% CI = 0.27-0.97, Z =- 2.07, p= 0.039). No statistically significant association of PSD with either heterozygous Short and Long allele genotype for the 5-HTTLPR or other polymorphisms with the RS25531 and the STin2 VNTR were found. Conclusion: Our meta-analysis suggests that the 5-HTTLPR SS genotype may be a risk factor for PSD while the 5-HTTLPR LL genotype may be a candidate protective factor against PSD

Personality Disorders, Violence, and Antisocial Behavior: A Systematic Review and Meta-Regression Analysis

The risk of antisocial outcomes in individuals with personality disorder (PD) remains uncertain. The authors synthesize the current evidence on the risks of antisocial behavior, violence, and repeat offending in PD, and they explore sources of heterogeneity in risk estimates through a systematic review and meta-regression analysis of observational studies comparing antisocial outcomes in personality disordered individuals with controls groups. Fourteen studies examined risk of antisocial and violent behavior in 10,007 individuals with PD, compared with over 12 million general population controls. There was a substantially increased risk of violent outcomes in studies with all PDs (random-effects pooled odds ratio [OR] = 3.0, 95% CI = 2.6 to 3.5). Meta-regression revealed that antisocial PD and gender were associated with higher risks (p = .01 and .07, respectively). The odds of all antisocial outcomes were also elevated. Twenty-five studies reported the risk of repeat offending in PD compared with other offenders. The risk of a repeat offense was also increased (fixed-effects pooled OR = 2.4, 95% CI = 2.2 to 2.7) in offenders with PD. The authors conclude that although PD is associated with antisocial outcomes and repeat offending, the risk appears to differ by PD category, gender, and whether individuals are offenders or not.

Effects of condom social marketing on condom use in developing countries: a systematic review and meta-analysis, 1990–2010

To examine the relationship between condom social marketing programmes and condom use. Standard systematic review and meta-analysis methods were followed. The review included studies of interventions in which condoms were sold, in which a local brand name(s) was developed for condoms, and in which condoms were marketed through a promotional campaign to increase sales. A definition of intervention was developed and standard inclusion criteria were followed in selecting studies. Data were extracted from each eligible study, and a meta-analysis of the results was carried out. Six studies with a combined sample size of 23,048 met the inclusion criteria. One was conducted in India and five in sub-Saharan Africa. All studies were cross-sectional or serial cross-sectional. Three studies had a comparison group, although all lacked equivalence in sociodemographic characteristics across study arms. All studies randomly selected participants for assessments, although none randomly assigned participants to intervention arms. The random-effects pooled odds ratio for condom use was 2.01 (95% confidence interval, CI: 1.42-2.84) for the most recent sexual encounter and 2.10 (95% CI: 1.51-2.91) for a composite of all condom use outcomes. Tests for heterogeneity yielded significant results for both meta-analyses. The evidence base for the effect of condom social marketing on condom use is small because few rigorous studies have been conducted. Meta-analyses showed a positive and statistically significant effect on increasing condom use, and all individual studies showed positive trends. The cumulative effect of condom social marketing over multiple years could be substantial. We strongly encourage more evaluations of these programmes with study designs of high rigour.

Obesity and knee osteoarthritis

The association between obesity and knee osteoarthritis, and specifically the role of obesity as a risk factor for knee osteoarthritis has been well documented. A systematic review and meta-analysis by Blagojevic et al. in Osteoarthr Cartil 18(1):24-33, (2010) examined 36 papers reporting on BMI and found that all studies demonstrated obesity and being overweight to be risk factors for knee osteoarthritis. The effect size for obesity as a risk factor for knee OA was reported to be I² = 97%, and the random effects pooled odds ratio for obesity compared to normal weight was 2.63 with a 95% CI of 2.28-3.05. This review summarises recent findings involving the association between knee osteoarthritis and obesity: the potential mechanisms of the link between the two disease states; and the potential benefits of weight loss on obese, knee osteoarthritis patients. Studies for inclusion in our report were identified using: MEDLINE; EMBASE; PUBMED; Cochrane Central Register of Controlled Trials; CINAHL; and reference lists of relevant articles. A number of recent studies involving the association between obesity and knee osteoarthritis have since been published. A large, population-based prospective study (n = 823) conducted by Toivanen et al. with a follow-up of 22 years found that the risk for knee osteoarthritis was 7 times greater for people with BMI ≥ 30 compared to the control of people with BMI <25. A prospective cohort study of the Norwegian population by Grotle et al. that followed 1,675 patients reported that BMI >30 was significantly associated with osteoarthritis of the knee, with odds ratio of 2.81, and 95% CI of 1.32-5.96. Lohmander et al. found that in a large cohort study of 27,960 patients from the Swedish population, the relative risk for knee osteoarthritis (fourth quartile compared to first quartile) was 8.1, with a 95% CI of 5.3-12.4. Finally, a case-control study from Holliday et al. with 1,042 knee osteoarthritis patients and 1,121 matched controls reported that the adjusted odds ratio for knee osteoarthritis in patients with BMI >30 was 7.48 with 95% CI of 5.45-10.27. Recent prospective studies demonstrate obesity as a primary risk factor for incident knee osteoarthritis. The potential mechanisms to link obesity and knee osteoarthritis, as both a biomechanical and metabolic condition are strongly linked. It has been established that weight loss for obese patients with knee osteoarthritis is clinically beneficial, for pain reduction, and for improved function. The exact mechanism linking obesity and osteoarthritis is complex; however, it is our opinion that further evidence supporting the link between the two diseases will be useful in providing clinicians and researchers with targets for physical therapy and pharmacological management of obese patients with knee osteoarthritis.

MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms

Association of two key variants mapping to the MTHFR gene (C677T (rs1801133) and A1298C (rs1801131)) with response to methotrexate (MTX) remains controversial. We investigated these and other markers spanning the gene as predictors of MTX efficacy and adverse events in a UK rheumatoid arthritis (RA) patient cohort and performed a meta-analysis of the two key variants using all published data. The tagging single nucleotide polymorphisms (SNPs) were genotyped in 309 patients with well-defined outcomes to MTX treatment and 17 studies were included in the meta-analysis. No association of the SNPs tested was detected with MTX efficacy or toxicity in our UK cohort. After combining our data with previous studies by meta-analysis, the random effects pooled odds ratios (OR) for both C677T and A1298C showed no association with efficacy or toxicity for either of the SNPs (efficacy: OR=1.05 (95% confidence interval (CI) 0.83-1.32) and OR=0.81 (95% CI 0.53-1.24), respectively; toxicity: OR=1.38 (95% CI 0.90-2.12) and OR=1.19 (95% CI 0.80-1.78), respectively). The available evidence suggests that the MTHFR C677T and A1298C gene polymorphisms are not reliable predictors of response to MTX treatment in RA patients.

Abortion and mental health: quantitative synthesis and analysis of research published 1995–2009

Given the methodological limitations of recently published qualitative reviews of abortion and mental health, a quantitative synthesis was deemed necessary to represent more accurately the published literature and to provide clarity to clinicians. To measure the association between abortion and indicators of adverse mental health, with subgroup effects calculated based on comparison groups (no abortion, unintended pregnancy delivered, pregnancy delivered) and particular outcomes. A secondary objective was to calculate population-attributable risk (PAR) statistics for each outcome. After the application of methodologically based selection criteria and extraction rules to minimise bias, the sample comprised 22 studies, 36 measures of effect and 877 181 participants (163 831 experienced an abortion). Random effects pooled odds ratios were computed using adjusted odds ratios from the original studies and PAR statistics were derived from the pooled odds ratios. Women who had undergone an abortion experienced an 81% increased risk of mental health problems, and nearly 10% of the incidence of mental health problems was shown to be attributable to abortion. The strongest subgroup estimates of increased risk occurred when abortion was compared with term pregnancy and when the outcomes pertained to substance use and suicidal behaviour. This review offers the largest quantitative estimate of mental health risks associated with abortion available in the world literature. Calling into question the conclusions from traditional reviews, the results revealed a moderate to highly increased risk of mental health problems after abortion. Consistent with the tenets of evidence-based medicine, this information should inform the delivery of abortion services.

Association of Folate-Pathway Gene Polymorphisms with the Risk of Prostate Cancer: a Population-Based Nested Case-Control Study, Systematic Review, and Meta-analysis

Folate-pathway gene polymorphisms have been implicated in several cancers and investigated inconclusively in relation to prostate cancer. We conducted a systematic review, which identified nine case-control studies (eight included, one excluded). We also included data from four genome-wide association studies and from a case-control study nested within the UK population-based Prostate Testing for Cancer and Treatment study. We investigated by meta-analysis the effects of eight polymorphisms: MTHFR C677T (rs1801133; 12 studies; 10,745 cases; 40,158 controls), MTHFR A1298C (rs1801131; 5 studies; 3,176 cases; 4,829 controls), MTR A2756G (rs1805087; 8 studies; 7,810 cases; 37,543 controls), MTRR A66G (rs1801394; 4 studies; 3,032 cases; 4,515 controls), MTHFD1 G1958A (rs2236225; 6 studies; 7,493 cases; 36,941 controls), SLC19A1/RFC1 G80A (rs1051266; 4 studies; 6,222 cases; 35,821 controls), SHMT1 C1420T (rs1979277; 2 studies; 2,689 cases; 4,110 controls), and FOLH1 T1561C (rs202676; 5 studies; 6,314 cases; 35,190 controls). The majority (10 of 13) of eligible studies had 100% Caucasian subjects; only one study had <90% Caucasian subjects. We found weak evidence of dominant effects of two alleles: MTR 2756A>G [random effects pooled odds ratio, 1.06 (1.00-1.12); P = 0.06 (P = 0.59 for heterogeneity across studies)] and SHMT1 1420C>T [random effects pooled odds ratio, 1.11 (1.00-1.22); P = 0.05 (P = 0.38 for heterogeneity across studies)]. We found no effect of MTHFR 677C>T or any of the other alleles in dominant, recessive or additive models, or in comparing a/a versus A/A homozygous. Neither did we find any difference in effects on advanced or localized cancers. Our meta-analysis suggests that known common folate-pathway single nucleotide polymorphisms do not have significant effects on susceptibility to prostate cancer.

Dose–response relationship of inhaled corticosteroids and cataracts: A systematic review and meta‐analysis

The risk of cataracts associated with the long-term use of inhaled corticosteroids (ICS) is poorly recognized, yet may be of major public health importance. The aim of this study was to determine the dose-response relationship of ICS use and risk of cataracts in adults. A systematic review and meta-analysis was performed of case-control studies of cataracts and ICS use, which included at least two doses of ICS and in which the number of cases and controls using each dose of ICS was reported. The primary outcome variable was risk of cataracts. Four case-control studies were identified, with a total of 46 638 cases and 146 378 controls. There was a significant relationship between the risk of cataracts and ICS dose, with a random effects pooled odds ratio for risk of cataracts per 1000 microg increase in daily beclomethasone dipropionate dose of 1.25 (95% CI: 1.14-1.37). The risk of cataracts was increased by approximately 25% for each 1000 microg per day increase in the dose of beclomethasone dipropionate or equivalent. These findings reinforce the importance of prescribing within the therapeutic dose-response range for ICS in asthma and the need to determine the dose-response relationship for the efficacy of ICS in COPD. Screening for the presence of cataracts could usefully be undertaken in older subjects with asthma and COPD, particularly current or ex-smokers.

MTHFR Gene Polymorphisms and Response to Chemotherapy in Colorectal Cancer: A Meta-Analysis

Pharmacogenetic studies investigating the relationship between MTHFR gene polymorphisms and response to fluorouracil-based chemotherapy in patients with colorectal cancer have produced inconclusive results. In an attempt to interpret these results, a meta-analysis of all eligible studies published up until January 2009 was carried out. A total of ten studies relating MTHFR C677T and six studies relating MTHFR A1298C to the response to chemotherapy in patients with colorectal cancer were included in the meta-analysis and random effects pooled odds ratios were estimated. The heterogeneity between studies, the sources of potential bias and the consistency of genetic effects across ethnicities were explored. Cumulative and recursive cumulative meta-analyses were also performed. For both the C677T and A1298C polymorphisms, the main analysis revealed nonsignificant heterogeneity and a lack of association under the allele contrast, the recessive and dominant models. The subgroup analysis by ethnicity did not change this pattern of results. The lack of stability of the relative change of odds ratio in the recursive cumulative meta-analysis for both polymorphisms indicated the need for more evidence to support a definite lack of association. There was no differential magnitude of the effect in large versus small studies. The available evidence indicates that MTHFR C677T and A1298C gene polymorphisms cannot be considered as reliable predictors of response to fluorouracil-based chemotherapy in patients with colorectal cancer.

Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-analysis of published series

It has been shown previously that IL-23R variants are associated with AS. We conducted an extended analysis in the UK population and a meta-analysis with the previously published studies, in order to refine these IL-23R associations with AS. The UK case-control study included 730 new cases and 1331 healthy controls. In the extended study, the 730 cases were combined with 1088 published cases. Allelic associations were analysed using contingency tables. In the meta-analysis, 3482 cases and 3150 controls from four different published studies and the new UK cases were combined. DerSimonian-Laird test was used to calculate random effects pooled odds ratios (ORs). In the UK case-control study with new cases, four of the eight SNPs showed significant associations, whereas in the extended UK study, seven of the eight IL-23R SNPs showed significant associations (P < 0.05) with AS, maximal with rs11209032 (P < 10(-5), OR 1.3), when cases with IBD and/or psoriasis were excluded. The meta-analysis showed significant associations with all eight SNPs; the strongest associations were again seen not only with rs11209032 (P = 4.06 x 10(-9), OR approximately 1.2) but also with rs11209026 (P < 10(-10), OR approximately 0.6). IL-23R polymorphisms are clearly associated with AS, but the primary causal association(s) is(are) still not established. These polymorphisms could contribute either increased or decreased susceptibility to AS; functional studies will be required for their full evaluation. Additionally, observed stronger associations with SNPs rs11209026 and rs11465804 upon exclusion of IBD and/or psoriasis cases may represent an independent association with AS.

Cruciferous vegetable consumption and lung cancer risk: a systematic review.

Cruciferous vegetables, rich in isothiocyanates, may protect against lung cancer. Glutathione S-transferases are important in metabolizing isothiocyanates; hence, variants in GST genes may modify the association between cruciferous vegetable intake and lung cancer. We carried out a systematic review to characterize the association between cruciferous vegetable intake and lung cancer risk, with an emphasis on the potential interaction between cruciferous vegetables and GSTM1 and GSTT1 gene variants. A search of the epidemiologic literature through December 2007 was conducted using 15 bibliographic databases without language restrictions. Thirty studies on the association between lung cancer and either total cruciferous vegetable consumption (6 cohort and 12 case-control studies) or specific cruciferous vegetables (1 cohort and 11 case-control studies) were included. The risk for lung cancer among those in the highest category of total cruciferous vegetable intake was 22% lower in case-control studies [random-effects pooled odds ratio, 0.78; 95% confidence interval (95% CI), 0.70-0.88] and 17% lower in cohort studies (pooled relative risk, 0.83; 95% CI, 0.62-1.08) compared with those in the lowest category of intake. The strongest inverse association of total cruciferous vegetable intake with lung cancer risk was seen among individuals with GSTM1 and GSTT1 double null genotypes (odds ratio, 0.41; 95% CI, 0.26-0.65; P for interaction = 0.01). Epidemiologic evidence suggests that cruciferous vegetable intake may be weakly and inversely associated with lung cancer risk. Because of a gene-diet interaction, the strongest inverse association was among those with homozygous deletion for GSTM1 and GSTT1.

Effects of l-Carnitine on Dialysis-Related Hypotension and Muscle Cramps: A Meta-analysis

L-Carnitine is an endogenous compound thought to be helpful in treating patients with dialysis-related hypotension and muscle cramps; however, sufficient evidence for these indications is lacking. Systematic review and meta-analysis. Adult patients with end-stage renal disease receiving long-term hemodialysis. All published English-language reports of randomized placebo-controlled trials of L-carnitine supplementation in adult long-term hemodialysis patients. Supplemental L-carnitine (or placebo) for at least 8 weeks. Random-effects pooled odds ratio for intradialytic cramping or hypotension in L-carnitine-treated participants. Of 317 potentially relevant articles, 7 (total enrollment of 193 patients) met criteria for inclusion. Four articles reported results for both hypotension and cramps, 1 had results for only hypotension, and 2 reported results for only cramps. Using data from all 6 relevant trials, the pooled odds ratio for cramping after L-carnitine supplementation was 0.30 (95% confidence interval, 0.09 to 1.00; P = 0.05). Analysis of the 5 studies examining the response of intradialytic hypotension to l-carnitine supplementation yielded a pooled odds ratio of 0.28 (95% confidence interval, 0.04 to 2.23; P = 0.2). The small number of available studies yielded limited statistical power. In addition, there was considerable interstudy heterogeneity. Although suggestive in the case of muscle cramping, the available evidence does not confirm a beneficial effect of L-carnitine supplementation on dialysis-related muscle cramping or intradialytic hypotension. Additional study in the form of large rigorous randomized trials is needed in both cases.