Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association ...between metformin and risk of cancer and cancer mortality in patients with diabetes.
MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers.
Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death 6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80, all malignancies 18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88, liver 8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60 colorectal 12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74-0.92, pancreas 9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36-0.86, stomach 2 studies, 100701 patients, OR:0.83, 95%CI: 0.76-0.91, and esophagus cancer 2 studies, 100694 patients, OR:0.90, 95%CI: 0.83-0.98. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma.
Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Confirmed Expanded Disability Status Scale (EDSS) progression occurring after a fixed-study entry baseline is a common measure of disability increase in relapsing-remitting multiple ...sclerosis (RRMS) studies but may not detect all disability progression events, especially those unrelated to overt relapses.
Objective:
To evaluate possible measures of disability progression unrelated to relapse using EDSS data over ≈5.5 years from the Tysabri® Observational Program (TOP).
Methods:
TOP is an ongoing, prospective, open-label study in RRMS patients receiving intravenous 300 mg natalizumab every 4 weeks. Measures of increasing disability were assessed using as a reference either study baseline score or a “roving” system that resets the reference score after ⩾24- or ⩾48-week confirmation of a new score.
Results:
This analysis included 5562 patients. Approximately 70% more EDSS progression events unrelated to relapse and 50% more EDSS worsening events overall were detected with a roving reference score (cumulative probability: 17.6% and 29.7%, respectively) than with a fixed reference baseline score (cumulative probability: 10.1% and 20.3%, respectively).
Conclusion:
In this long-term observational RRMS dataset, a roving EDSS reference value was more efficient than a study baseline EDSS reference in detecting progression/worsening events unrelated to relapses and thus the transition to secondary progressive disease.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined.
Objective:
The aim of ...this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network.
Methods:
Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference.
Results:
A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower (p < 0.0004) for the first quintile patients’ group.
Conclusion:
Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
Propensity score (PS) analyses are increasingly used in multiple sclerosis (MS) research, largely owing to the greater availability of large observational cohorts and registry databases.
...Objective:
To evaluate the use and quality of reporting of PS methods in the recent MS literature.
Methods:
We searched the PubMed database for articles published between January 2013 and July 2019. We restricted the search to comparative effectiveness studies of two disease-modifying therapies.
Results:
Thirty-nine studies were included in the review, with most studies (62%) published within the past 3 years. All studies reported the list of covariates used for the PS model, but only 21% of studies mentioned how those covariates were selected. Most studies used PS matching (72%), followed by PS adjustment (18%), weighting (15%), and stratification (3%), with some overlap. Most studies using matching or weighting reported checking post-PS covariate imbalance (91%), although about 45% of these studies relied on p values from various statistical tests. Only 25% of studies using matching reported calculating robust standard errors for the PS analyses.
Conclusions:
The quality of reporting of PS methods in the MS literature is sub-optimal in general, and in some cases, inappropriate methods are used.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
Stratified medicine methodologies based on subgroup analyses are often insufficiently powered. More powerful personalized medicine approaches are based on continuous scores.
Objective:
We ...deployed a patient-specific continuous score predicting treatment response in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods:
Data from two independent randomized controlled trials (RCTs) were used to build and validate an individual treatment response (ITR) score, regressing annualized relapse rates (ARRs) on a set of baseline predictors.
Results:
The ITR score for the combined treatment groups versus placebo detected differential clinical response in both RCTs. High responders in one RCT had a cross-validated ARR ratio of 0.29 (95% confidence interval (CI) = 0.13–0.55) versus 0.62 (95% CI = 0.47–0.83) for all other responders (heterogeneity p = 0.038) and were validated in the other RCT, with the corresponding ARR ratios of 0.31 (95% CI = 0.18–0.56) and 0.61 (95% CI = 0.47–0.79; heterogeneity p = 0.036). The strongest treatment effect modifiers were the Short Form-36 Physical Component Summary, age, Visual Function Test 2.5%, prior MS treatment and Expanded Disability Status Scale.
Conclusion:
Our modelling strategy detects and validates an ITR score and opens up avenues for building treatment response calculators that are also applicable in routine clinical practice.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Altered expression of microRNAs (miRNAs) hallmarks many cancer types. The study of the associations of miRNA expression profile and cancer phenotype could help identify the links between deregulation ...of miRNA expression and oncogenic pathways.
Expression profiling of 866 human miRNAs in 19 colorectal and 17 pancreatic cancers and in matched adjacent normal tissues was investigated. Classical paired t-test and random forest analyses were applied to identify miRNAs associated with tissue-specific tumors. Network analysis based on a computational approach to mine associations between cancer types and miRNAs was performed.
The merge between the two statistical methods used to intersect the miRNAs differentially expressed in colon and pancreatic cancers allowed the identification of cancer-specific miRNA alterations. By miRNA-network analysis, tissue-specific patterns of miRNA deregulation were traced: the driving miRNAs were miR-195, miR-1280, miR-140-3p and miR-1246 in colorectal tumors, and miR-103, miR-23a and miR-15b in pancreatic cancers.
MiRNA expression profiles may identify cancer-specific signatures and potentially useful biomarkers for the diagnosis of tissue specific cancers. miRNA-network analysis help identify altered miRNA regulatory networks that could play a role in tumor pathogenesis.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Calcimimetic agents lower serum parathyroid hormone levels in people with chronic kidney disease (CKD), but treatment effects on patient-relevant outcomes are uncertain. We conducted a systematic ...review and meta-analysis to summarize the benefits and harms of calcimimetic therapy in adults with CKD and used cumulative meta-analysis to identify how evidence for calcimimetic treatment has developed in this clinical setting.
Cochrane and Embase databases (through February 7, 2013) were electronically searched to identify randomized trials evaluating effects of calcimimetic therapy on mortality and adverse events in adults with CKD. Two independent reviewers identified trials, extracted data, and assessed risk of bias. Eighteen trials comprising 7,446 participants compared cinacalcet plus conventional therapy with placebo or no treatment plus conventional therapy in adults with CKD. In moderate- to high-quality evidence (based on Grading of Recommendations Assessment, Development, and Evaluation criteria) in adults with CKD stage 5D (dialysis), cinacalcet had little or no effect on all-cause mortality (relative risk, 0.97 95% confidence interval, 0.89-1.05), had imprecise effect on cardiovascular mortality (0.67 0.16-2.87), and prevented parathyroidectomy (0.49 0.40-0.59) and hypercalcemia (0.23 0.05-0.97), but increased hypocalcemia (6.98 5.10-9.53), nausea (2.02 1.45-2.81), and vomiting (1.97 1.73-2.24). Data for clinical outcomes were sparse in adults with CKD stages 3-5. On average, treating 1,000 people with CKD stage 5D for 1 y had no effect on survival and prevented about three patients from experiencing parathyroidectomy, whilst 60 experienced hypocalcemia and 150 experienced nausea. Analyses were limited by insufficient data in CKD stages 3-5 and kidney transplant recipients.
Cinacalcet reduces the need for parathyroidectomy in patients with CKD stage 5D, but does not appear to improve all-cause or cardiovascular mortality. Additional trials in CKD stage 5D are unlikely to change our confidence in the treatment effects of cinacalcet in this population.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
With many disease-modifying therapies currently approved for the management of multiple sclerosis, there is a growing need to evaluate the comparative effectiveness and safety of those ...therapies from real-world data sources. Propensity score methods have recently gained popularity in multiple sclerosis research to generate real-world evidence. Recent evidence suggests, however, that the conduct and reporting of propensity score analyses are often suboptimal in multiple sclerosis studies.
Objectives:
To provide practical guidance to clinicians and researchers on the use of propensity score methods within the context of multiple sclerosis research.
Methods:
We summarize recommendations on the use of propensity score matching and weighting based on the current methodological literature, and provide examples of good practice.
Results:
Step-by-step recommendations are presented, starting with covariate selection and propensity score estimation, followed by guidance on the assessment of covariate balance and implementation of propensity score matching and weighting. Finally, we focus on treatment effect estimation and sensitivity analyses.
Conclusion:
This comprehensive set of recommendations highlights key elements that require careful attention when using propensity score methods.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background Depression occurs relatively commonly in people with chronic kidney disease (CKD), but it is uncertain whether depression is a risk factor for premature death in this population. ...Interventions to reduce mortality in CKD consistently have been ineffective and new strategies are needed. Study Design Systematic review and meta-analysis of cohort studies. Setting & Population Adults with CKD. Selection Criteria for Studies Cohort studies identified in Ovid MEDLINE through week 3 December 2012 without language restriction. Predictor Depression status as determined by physician diagnosis, clinical coding, or self-reported scales. Selection Criteria for Studies All-cause and cardiovascular mortality. Outcomes were summarized as relative risks (RRs) with 95% CIs using random-effects meta-analysis. Results 22 studies (83,381 participants) comprising 12,063 cases of depression (mean prevalence, 27.4%; 95% CI, 20.0%-36.3%) with a follow-up of 3 months to 6.5 years were included. Methodological quality generally was good or fair. Depression consistently increased the risk of death from any cause (RR, 1.59; 95% CI, 1.35-1.87), but had less certain effects on cardiovascular mortality (RR, 1.88; 95% CI, 0.84-4.19). Associations for mortality were similar regardless of the diagnostic method used for depression, but were weaker in analyses controlled for preexisting cardiovascular disease (RR, 1.36; 95% CI, 1.23-1.50). Limitations Meta-analyses adjusting for antidepressant medication use were not possible, and data for kidney transplant recipients and individuals with earlier stages of CKD not treated with dialysis were limited. Conclusions Depression is associated with a substantially increased risk of death in people with CKD. Effective treatment for depression in people with CKD may reduce mortality.
Studies concerning the association between circulating resistin and mortality risk have reported, so far, conflicting results.
To investigate the association between resistin and both all-cause and ...cardiovascular (CV) mortality risk by 1) analyzing data from the Gargano Heart Study (GHS) prospective design (n=359 patients; 81 and 58 all-cause and CV deaths, respectively); 2) performing meta-analyses of all published studies addressing the above mentioned associations.
MEDLINE and Web of Science search of studies reporting hazard ratios (HR) of circulating resistin for all-cause or CV mortality.
Performed independently by two investigators, using a standardized data extraction sheet.
In GHS, adjusted HRs per one standard deviation (SD) increment in resistin concentration were 1.28 (95% CI: 1.07-1.54) and 1.32 (95% CI: 1.06-1.64) for all-cause and CV mortality, respectively. The meta-analyses included 7 studies (n=4016; 961 events) for all-cause mortality and 6 studies (n=4,187: 412 events) for CV mortality. Pooled HRs per one SD increment in resistin levels were 1.21 (95% CI: 1.03-1.42, Q-test p for heterogeneity<0.001) and 1.05 (95% CI: 1.01-1.10, Q-test p for heterogeneity=0.199) for all-cause and CV mortality, respectively. At meta-regression analyses, study mean age explained 9.9% of all-cause mortality studies heterogeneity. After adjusting for age, HR for all-cause mortality was 1.24 (95% CI: 1.06-1.45).
Our results provide evidence for an association between circulating resistin and mortality risk among high-risk patients as are those with diabetes and coronary artery disease.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
