As newer oral diabetes agents continue to emerge on the market, comparative evidence is urgently required to guide appropriate therapy.
To summarize the English-language literature on the benefits ...and harms of oral agents (second-generation sulfonylureas, biguanides, thiazolidinediones, meglitinides, and alpha-glucosidase inhibitors) in the treatment of adults with type 2 diabetes mellitus.
The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched from inception through January 2006 for original articles and through November 2005 for systematic reviews. Unpublished U.S. Food and Drug Administration and industry data were also searched.
216 controlled trials and cohort studies and 2 systematic reviews that addressed benefits and harms of oral diabetes drug classes available in the United States.
Using standardized protocols, 2 reviewers serially abstracted data for each article.
Evidence from clinical trials was inconclusive on major clinical end points, such as cardiovascular mortality. Therefore, the review was limited mainly to studies of intermediate end points. Most oral agents (thiazolidinediones, metformin, and repaglinide) improved glycemic control to the same degree as sulfonylureas (absolute decrease in hemoglobin A1c level of about 1 percentage point). Nateglinide and alpha-glucosidase inhibitors may have slightly weaker effects, on the basis of indirect comparisons of placebo-controlled trials. Thiazolidinediones were the only class that had a beneficial effect on high-density lipoprotein cholesterol levels (mean relative increase, 0.08 to 0.13 mmol/L 3 to 5 mg/dL) but a harmful effect on low-density lipoprotein (LDL) cholesterol levels (mean relative increase, 0.26 mmol/L 10 mg/dL) compared with other oral agents. Metformin decreased LDL cholesterol levels by about 0.26 mmol/L (10 mg/dL), whereas other oral agents had no obvious effects on LDL cholesterol levels. Most agents other than metformin increased body weight by 1 to 5 kg. Sulfonylureas and repaglinide were associated with greater risk for hypoglycemia, thiazolidinediones with greater risk for heart failure, and metformin with greater risk for gastrointestinal problems compared with other oral agents. Lactic acidosis was no more common in metformin recipients without comorbid conditions than in recipients of other oral diabetes agents.
Data on major clinical end points were limited. Studies inconsistently reported adverse events other than hypoglycemia, and definitions of adverse events varied across studies. Some harms not assessed in trials or observational studies may have been overlooked.
Compared with newer, more expensive agents (thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides), older agents (second-generation sulfonylureas and metformin) have similar or superior effects on glycemic control, lipids, and other intermediate end points. Large, long-term comparative studies are needed to determine the comparative effects of oral diabetes agents on hard clinical end points.
Risk-of-bias assessment is a central component of systematic reviews, but little conclusive empirical evidence exists on the validity of such assessments. In the context of such uncertainty, we ...present pragmatic recommendations that promote transparency and reproducibility in processes, address methodological advances in the risk-of-bias assessment, and can be applied consistently across review topics.
Epidemiological study design principles; available empirical evidence, risk-of-bias tools, and guidance; and workgroup consensus.
We developed recommendations for assessing the risk of bias of studies of health-care interventions specific to framing the focus and scope of risk-of-bias assessment; selecting the risk-of-bias categories; choosing assessment instruments; and conducting, analyzing, and presenting results of risk-of-bias assessments. Key recommendations include transparency and reproducibility of judgments, separating risk of bias from other constructs such as applicability and precision, and evaluating the risk of bias per outcome. We recommend against certain past practices, such as focusing on reporting quality, relying solely on study design or numerical quality scores, and automatically downgrading for industry sponsorship.
Risk-of-bias assessment remains a challenging but essential step in systematic reviews. We presented standards to promote transparency of judgments.
Patients with diabetes mellitus need information about the effectiveness of innovations in insulin delivery and glucose monitoring.
To review how intensive insulin therapy (multiple daily injections ...MDI vs. rapid-acting analogue-based continuous subcutaneous insulin infusion CSII) or method of monitoring (self-monitoring of blood glucose SMBG vs. real-time continuous glucose monitoring rt-CGM) affects outcomes in types 1 and 2 diabetes mellitus.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2012 without language restrictions.
33 randomized, controlled trials in children or adults that compared CSII with MDI (n=19), rt-CGM with SMBG (n=10), or sensor-augmented insulin pump use with MDI and SMBG (n=4).
2 reviewers independently evaluated studies for eligibility and quality and serially abstracted data.
In randomized, controlled trials, MDI and CSII showed similar effects on hemoglobin A1c (HbA1c) levels and severe hypoglycemia in children or adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus. In adults with type 1 diabetes mellitus, HbA1c levels decreased more with CSII than with MDI, but 1 study heavily influenced these results. Compared with SMBG, rt-CGM achieved a lower HbA1c level (between-group difference of change, 0.26% 95% CI, 0.33% to 0.19%) without any difference in severe hypoglycemia. Sensor-augmented insulin pump use decreased HbA1c levels more than MDI and SMBG did in persons with type 1 diabetes mellitus (between-group difference of change, 0.68% CI, 0.81% to 0.54%). Little evidence was available on other outcomes.
Many studies were small, of short duration, and limited to white persons with type 1 diabetes mellitus.
Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia.
Agency for Healthcare Research and Quality.
Abstract Objectives To revise 2010 guidance on grading the strength of evidence (SOE) of the effectiveness of drugs, devices, and other preventive and therapeutic interventions in systematic reviews ...produced by the Evidence-based Practice Center (EPC) program, established by the US Agency for Healthcare Research and Quality (AHRQ). Study Design and Setting A cross-EPC working group reviewed authoritative systems for grading SOE primarily the approach from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group and conducted extensive discussions with GRADE and other experts. Results Updated guidance continues to be conceptually similar to GRADE. Reviewers are to evaluate SOE separately for each major treatment comparison for each major outcome. We added reporting bias as a required domain and retained study limitations (risk of bias), consistency, directness, and precision (and three optional domains). Additional guidance covers scoring consistency, precision, and reporting bias, grading bodies of evidence with randomized controlled trials and observational studies, evaluating single study bodies of evidence, using studies with high risk of bias, and presenting findings with greater clarity and transparency. SOE is graded high, moderate, low, or insufficient, reflecting reviewers' confidence in the findings for a specific treatment comparison and outcome. Conclusion No single approach for grading SOE suits all reviews, but a more consistent and transparent approach to reporting summary information will make reviews more useful to the broad range of audiences that AHRQ's work aims to reach. EPC working groups will consider ongoing challenges and modify guidance as needed, on issues such as combining trials and observational studies in bodies of evidence, weighting domains, and combining qualitative and quantitative syntheses.
Clinicians face uncertainty about the prognostic value of troponin testing in patients with chronic kidney disease (CKD) without suspected acute coronary syndrome (ACS).
To systematically review the ...literature on troponin testing in patients with CKD without ACS.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through May 2014.
Studies examining elevated versus normal troponin levels in patients with CKD without ACS.
Paired reviewers selected articles for inclusion, extracted data, and graded strength of evidence (SOE). Meta-analyses were conducted when studies had sufficient homogeneity of key variables.
Ninety-eight studies met inclusion criteria. Elevated troponin levels were associated with all-cause and cardiovascular mortality among patients receiving dialysis (moderate SOE). Pooled hazard ratios (HRs) for all-cause mortality from studies that adjusted for age and coronary artery disease or a risk equivalent were 3.0 (95% CI, 2.4 to 4.3) for troponin T and 2.7 (CI, 1.9 to 4.6) for troponin I. The pooled adjusted HRs for cardiovascular mortality were 3.3 (CI, 1.8 to 5.4) for troponin T and 4.2 (CI, 2.0 to 9.2) for troponin I. Findings were similar for patients with CKD who were not receiving dialysis, but there were fewer studies. No study tested treatment strategies by troponin cut points.
Studies were heterogeneous regarding assays, troponin cut points, covariate adjustment, and follow-up.
In patients with CKD without suspected ACS, elevated troponin levels were associated with worse prognosis. Future studies should focus on whether this biomarker is more appropriate than clinical models for reclassifying risk of patients with CKD and whether such classification can help guide treatment in those at highest risk for death.
Agency for Healthcare Research and Quality.
Iodine contrast media are essential components of many imaging procedures. An important potential side effect is contrast-induced nephropathy (CIN).
To compare CIN risk for contrast media within and ...between osmolality classes in patients receiving diagnostic or therapeutic imaging procedures.
PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Scopus through June 2015.
Randomized, controlled trials that reported CIN-related outcomes in patients receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media for imaging.
Independent study selection and quality assessment by 2 reviewers and dual extraction of study characteristics and results.
None of the 5 studies that compared types of LOCM reported a statistically significant or clinically important difference among study groups, but the strength of evidence was low. Twenty-five randomized, controlled trials found a slight reduction in CIN risk with the iso-osmolar contrast media agent iodixanol compared with a diverse group of LOCM that just reached statistical significance in a meta-analysis (pooled relative risk, 0.80 95% CI, 0.65 to 0.99; P = 0.045). This comparison's strength of evidence was moderate. In a meta regression of randomized, controlled trials of iodixanol, no relationship was found between route of administration and comparative CIN risk.
Few studies compared LOCM. Procedural details about contrast administration were not uniformly reported. Few studies specified clinical indications or severity of baseline renal impairment.
No differences were found in CIN risk among types of LOCM. Iodixanol had a slightly lower risk for CIN than LOCM, but the lower risk did not exceed a criterion for clinical importance.
Agency for Healthcare Research and Quality.
Abstract Context can influence cancer-related outcomes. For example, health-care organization characteristics, including ownership, leadership, and culture, can affect care access, communication, and ...patient outcomes. Health-care organization characteristics and other contextual factors can also influence whether and how clinical discoveries reduce cancer incidence, morbidity, and mortality. Importantly, policy, market, and technology changes are transforming health-care organization design, culture, and operations across the cancer continuum. Consequently, research is essential to examine when, for whom, and how organizational characteristics influence person-level, organization-level, and population-level cancer outcomes. Understanding organizational characteristics—the structures, processes, and other features of entities involved in health care delivery—and their dynamics is an important yet understudied area of care delivery research across the cancer continuum. Research incorporating organizational characteristics is critical to address health inequities, test care delivery models, adapt interventions, and strengthen implementation. The field lacks conceptual grounding, however, to help researchers identify germane organizational characteristics. We propose a framework identifying organizational characteristics relevant for cancer care delivery research based on conceptual work in health services, organizational behavior, and management science and refined using a systematic review and key informant input. The proposed framework is a tool for organizing existing research and enhancing future cancer care delivery research. Following a 2012 Journal of the National Cancer Institute monograph, this work complements National Cancer Institute efforts to stimulate research addressing the relationship between cancer outcomes and contextual factors at the patient, provider, team, delivery organization, community, and health policy levels.
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