The quality of clinical practice guidelines for management of pediatric type 2 diabetes mellitus: a systematic review using the AGREE II instrument.

AIMS: Pediatric type 2 diabetes mellitus (T2DM) is a relatively new disease with increasing incidence corresponding to the obesity epidemic among youth. It is important for clinicians to have access to high-quality clinical practice guidelines (CPGs) for appropriate management of pediatric patients with T2DM. The objective of this systematic review was to evaluate overall quality of CPGs for the management of pediatric T2DM using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. METHODS: We searched MEDLINE, Embase, CINAHL, Trip, National Guideline Clearinghouse, and grey literature to identify eligible CPGs. We also searched the webpages of national and international diabetes and pediatric organizations globally. We included CPGs from national and international diabetes and pediatric associations that were published as standalone guidelines for T2DM in children and adolescents (2-18 years of age). We also included pediatric and adult guidelines for type 1 diabetes if they included a section addressing T2DM management in children and adolescents. We retrieved the two most recent guidelines from each organization when available to assess change in quality over time. We excluded individual studies and systematic reviews that made treatment recommendations as well as CPGs that were developed for a single institution. RESULTS: We included 21 unique CPGs in this systematic review. Of the included guidelines, 12 were developed or updated between 2012 and 2014. Five of all included CPGs were specific to pediatric populations. The analysis revealed that "Rigour of Development" (mean 45%, SD 28.68) and "Editorial Independence" (mean 45%, SD 35.19) were the lowest scoring domains on the AGREE II for the majority of guidelines, whereas "Clarity of Presentation" was the highest scoring domain (mean 72%, SD 18.89). CONCLUSIONS: Overall, two thirds of the pediatric T2DM guidelines were moderate to low quality and the remaining third ranked higher in quality. Low quality was especially due to the scores for the "Rigour of Development" domain, which directly measures guideline development methodology. It is important that future guidelines and updates of existing guidelines improve the methodology of development and quality of reporting in order to appropriately guide physicians managing children and adolescents with T2DM. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016034187.

Adoption and outcomes of radioguided seed localization for non-palpable invasive and in-situ breast cancer at three academic tertiary care centers.

INTRODUCTION: Radioguided seed localization (RSL) is an alternative technique to wire-guided localization (WL) for localizing non-palpable breast lesions for breast conserving surgery. The purpose of this study was to assess adoption and outcomes of RSL at 3 academic hospitals in our city. METHODS: Data for consecutive invasive and in-situ breast cancer cases localized with RSL or WL at 3 hospitals between January 2012 and February 2016 were abstracted. Data analysis was conducted using the Student's t-test, ANOVA with Tukey's HSD test for post-hoc multiple comparisons, and chi-squared test. RESULTS: There were 803 consecutive cases. Hospital 1 exclusively used RSL (247 cases), whereas H2 adopted RSL (109 cases), but continued to use WL (347 cases). Hospital 3 exclusively used WL (100 cases). There was no difference between RSL and WL groups in positive margin rate (p = 0.337), re-operation (p = 0.413), or mean specimen volume (p = 0.190). DISCUSSION: There has been variable adoption of RSL in our city. Despite this, relevant surgical outcomes have been similar across groups. The causes of variable adoption of this novel technique merit further investigation.

A prospective functional MRI study for executive function in patients with systemic lupus erythematosus without neuropsychiatric symptoms.

OBJECTIVE: To study the functional brain activation signals before and after sufficient disease control in patients with systemic lupus erythematosus (SLE) without clinical neuropsychiatric symptoms. METHODS: Blood-oxygen-level-dependent signals during event-related functional magnetic resonance imaging brain were recorded, while 14 new-onset SLE patients and 14 demographically and intelligence quotient matched healthy controls performed the computer-based Wisconsin card sorting test for assessing executive function, which probes strategic planning and goal-directed task performance during feedback evaluation (FE) and response selection (RS), respectively. Composite beta maps were constructed by a general linear model to identify regions of cortical activation. Blood-oxygen-level-dependent functional magnetic resonance imaging signals were compared between (1) new-onset SLE patients and healthy controls and (2) SLE patients before and after sufficient control of their disease activity. RESULTS: During RS, SLE patients demonstrated significantly higher activation than healthy controls in both caudate bodies and Brodmann area (BA) 9 to enhance event anticipation, attention, and working memory, respectively, to compensate for the reduced activation during FE in BA6, 13, 24, and 32, which serve complex motor planning and decision-making, sensory integration, error detection, and conflict processing, respectively. Despite significant reduction of SLE activity, BA32 was activated during RS to compensate for reduced activation during FE in BA6, 9, 37, and 23/32, which serve motor planning, response inhibition and attention, color processing and word recognition, error detection, and conflict evaluation, respectively. CONCLUSIONS: Even without clinically overt neuropsychiatric symptoms, SLE patients recruited additional pathways to execute goal-directed tasks to compensate for their reduced strategic planning skill despite clinically sufficient disease control.

Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression.

OBJECTIVE: [corrected] High homocysteine (Hct) has been causatively linked to Alzheimer disease (AD) and vascular dementia (VaD) in old age, but research methodologies and outcome measures are heterogeneous. It remains unclear whether the findings can be generalized across studies. METHODS: Random-effects meta-analyses were conducted on studies examining the relationship between Hct level and risk of developing dementia/cognitive decline between comparison groups. Meta-regression identified patient- and trial-related factors, which may contribute to heterogeneity. RESULTS: Seventeen relevant studies (6,122 participants; 13 cross-sectional and fourprospective studies) were included. Compared with controls, Hct was significantly elevated in AD (pooled standardized mean difference [SMD]: 0.59; 95% confidence interval [CI]: 0.38-0.80; significant heterogeneity: τ = 0.105) and VaD (pooled SMD: 1.30; 95% CI: 0.75-1.84; significant heterogeneity: τ = 0.378). Meta-regression identified mean age as significant moderator for AD versus controls and mean age and mean folate levels as significant moderators for VaD versus controls. Hct was significantly higher in VaD relative to AD (pooled SMD: 0.48; 95% CI: 0.23-0.73; moderately significant heterogeneity: τ = 0.076); proportion of men and mean folate levels were significant moderators. High-Hct level was not associated with risk of developing dementia in prospective studies (pooled odds ratio: 1.34; 95% CI: 0.94-1.91, nonsignificant heterogeneity: τ = 0.048). CONCLUSION: Individuals with AD and VaD have higher Hct levels than controls; however, a causal relationship between high-Hct level and risk of developing dementia is not supported. More prospective studies and randomized controlled trials are required to test the therapeutic benefits of lowering Hct levels.

Prevalence of depressive symptoms in patients with chronic obstructive pulmonary disease: a systematic review, meta-analysis and meta-regression.

OBJECTIVE: This meta-analysis was aimed to evaluate the differences in aggregated prevalence of depressive symptoms among people with chronic obstructive pulmonary disease (COPD) as compared to controls without COPD and to determine underlying moderators to explain potential heterogeneity of prevalence. METHODS: A meta-analysis of published work was performed using the random effect model. A total of eight studies were identified. We calculated the differences in prevalence proportion of depressive symptoms in patients with COPD versus controls. Meta-regression and subgroup analysis were performed to identify factors that may contribute to heterogeneity. RESULTS: The prevalence proportion of depressive symptoms was found to be significantly higher (pooled odds ratio: 2.81; 95% CI: 1.69-4.66) among 39587 individuals with COPD as compared to 39,431 controls (24.6%, 95% CI: 20.0-28.6% vs. 11.7%, 95% CI: 9-15.1%). Meta-regression was conducted to account for the heterogeneity of the prevalence proportion, but moderators like mean age, gender, mean FEV(1) and proportion of current smokers among COPD patients were nonsignificant and could not explain heterogeneity in prevalence of depressive symptoms. Subgroup analyses showed no significant differences based on different methods of assessment of depressive symptoms and countries sampled. CONCLUSION: This meta-analytical review identified higher prevalence of depressive symptoms among COPD patients, and meta-regression showed that demographic and clinical factors were not the determinants of heterogeneity in prevalence of depressive symptoms.

Clinical and psychosocial factors associated with depression and anxiety in Singaporean patients with rheumatoid arthritis.

AIM: To assess the frequency of, and factors associated with, depression and anxiety in Singaporean patients with rheumatoid arthritis (RA). METHOD: One hundred RA patients were recruited in a cross-sectional study. Socio-demographics, severity of anxiety and depression, disease activity, levels of serological markers and health-related quality of life were analyzed. RESULTS: Twenty-six percent presented with anxiety, 15% with depression and 11% with both. Univariate regression showed that age (P = 0.039), Disease Activity Scale (DAS-28) (P < 0.001), number of medications (P < 0.001) and rheumatoid factor (RF) (P < 0.001) were positively associated with severity of depression, while income (P = 0.001), education (P = 0.029), self-perceived social support (P = 0.007), Short form 12 (SF-12) physical health (P < 0.001) and SF-12 mental health (P < 0.001) were negatively associated with severity of depression. After adjustment for confounding factors in multivariate regression, income (ß = -0.347, P = 0.018), RF (ß = 0.304, P = 0.043) and SF-12 mental health (ß = -0.501 P = 0.001) remained significantly associated with depression. Univariate regression showed that DAS-28 (P = 0.009), number of medications (P = 0.004) and RF (P = 0.043) were positively associated with anxiety, while income (P = 0.022), self-perceived social support (P = 0.04), SF-12 physical health (P < 0.001) and SF-12 mental health (P < 0.001) were negatively associated with anxiety. After adjustment for confounding factors, no factors remained significantly associated with anxiety. CONCLUSION: Low income, high levels of RF and poor mental health were associated with depression in RA. Our findings may help to formulate depression screening strategies. Further research is required to identify the role of RF in depression.

Meta-analysis in medicine: an introduction.

Meta-analysis, a complex statistical method which involves synthesis of data from relevant studies to devise an effect size or a conclusion, has increasingly been recognized and impacts on evidence-based medicine, especially in the field of health science. Thanks to the advent and unmet need of evidence-based medicine, since the first recordable publication of a meta-analysis in 1904 addressing the effectiveness of typhoid vaccine, both the number and quality of meta-analyses published relating to healthcare science have been on a steep rise. If properly conducted, based on answering relevant clinical questions, strict selection criteria of participating studies, appropriate analytical methods, and proper presentation of results, coupled with critical and faithful discussion on the strength and weakness of the analysis, meta-analysis will definitely be an invaluable tool for clinicians and researchers in understanding epidemiology, justifying and refining hypotheses of various diseases, for medical practitioners to implement sound management decisions based on evidence-based medicine, and ultimately, for policy-makers to formulate cost-efficient treatment strategies, guidelines and legislation. In this first paper of a mini-series, the current trend of meta-analysis publications in the medical literature, examples of important meta-analyses relevant to rheumatology and the pros and cons of meta-analysis, will be discussed. Important terminology related to meta-analysis, the systematic ways to critically appraise, and finally the preferred methodology of conducting meta-analysis will be covered in the subsequent three reviews of this mini-series.