Out of context: clinical practice guidelines and patients with multiple chronic conditions: a systematic review.

BACKGROUND: Poor fidelity to practice guidelines in the care of people with multiple chronic conditions (MCC) may result from patients and clinicians struggling to apply recommendations that do not consider the interplay of MCC, socio-personal context, and patient preferences. OBJECTIVE: The objective of the study was to assess the quality of guideline development and the extent to which guidelines take into account 3 important factors: the impact of MCC, patients' socio-personal contexts, and patients' personal values and preferences. RESEARCH DESIGN: We conducted a systematic search of clinical practice guidelines for patients with type 2 diabetes mellitus published between 2006 and 2012. Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, EBSCO CINAHL, and the National Guideline Clearinghouse were searched. Two reviewers working independently selected studies, extracted data, and evaluated the quality of the guidelines. RESULTS: We found 28 eligible guidelines, which, on average, had major methodological limitations (AGREE II mean score 3.8 of 7, SD=1.6). Patients or methodologists were not included in the guideline development process in 20 (71%) and 24 (86%) guidelines, respectively. There was a complete absence of incorporating the impact of MCC, socio-personal context, and patient preferences in 8 (29%), 11 (39%), and 16 (57%) of the 28 guidelines, respectively. When mentioned, MCC were considered biologically, but not as contributors of complexity or patient work or as motivation to focus on patient-centered outcomes. CONCLUSIONS: Extant clinical practice guidelines for one chronic disease sometimes consider the context of the patient with that disease, but only do so narrowly. Guideline panels must remove their contextual blinders if they want to practically guide the care of patients with MCC.

Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis.

CONTEXT: Osteoporosis and osteopenia are associated with increased fracture incidence. OBJECTIVE: The aim of this study was to determine the comparative effectiveness of different pharmacological agents in reducing the risk of fragility fractures. DATA SOURCES: We searched multiple databases through 12/9/2011. STUDY SELECTION: Eligible studies were randomized controlled trials enrolling individuals at risk of developing fragility fractures and evaluating the efficacy of bisphosphonates, teriparatide, selective estrogen receptor modulators, denosumab, or calcium and vitamin D. DATA EXTRACTION: Reviewers working independently and in duplicate determined study eligibility and collected descriptive, methodological quality, and outcome data. DATA SYNTHESIS: This network meta-analysis included 116 trials (139,647 patients; median age, 64 yr; 86% females and 88% Caucasians; median follow-up, 24 months). Trials were at low to moderate risk of bias. Teriparatide had the highest risk reduction of fractures (odds ratios, 0.42, 0.30, and 0.50 for hip, vertebral, and nonvertebral fractures, respectively) and the highest probability of being ranked first for efficacy (probabilities of 42, 49, and 79% for hip, vertebral, and nonvertebral fractures, respectively). However, differences to denosumab, zoledronate, risedronate, ibandronate, and alendronate were not statistically significant. Raloxifene and bazedoxifene were likely less effective, although these data were limited. Calcium and vitamin D were ineffective given separately but reduced the risk of hip fractures if given in combination (odds ratio, 0.81; 95% confidence interval, 0.68­0.96). CONCLUSIONS: Teriparatide, bisphosphonates, and denosumab are most effective in reducing the risk of fragility fractures. Differences in efficacy across drugs are small; therefore, patients and clinicians need to consider their associated harms and costs.

Clinical review. Risk factors for low bone mass-related fractures in men: a systematic review and meta-analysis.

CONTEXT: Testing men at increased risk for osteoporotic fractures has been recommended. OBJECTIVE: The aim of this study was to estimate the magnitude of association and quality of supporting evidence linking multiple risk factors with low bone mass-related fractures in men. DATA SOURCES: We searched MEDLINE, EMBASE, Web of Science, SCOPUS and Cochrane CENTRAL through February 2010. We identified further studies by reviewing reference lists from selected studies and reviews. STUDY SELECTION: Eligible studies had to enroll men and quantitatively evaluate the association of risk factors with low bone density-related fractures. DATA EXTRACTION: Reviewers working independently and in duplicate determined study eligibility and extracted study description, quality, and outcome data. DATA SYNTHESIS: Fifty-five studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate with fair levels of multivariable adjustment and adequate exposure and outcome ascertainment. Statistically significant associations were established for age, low body mass index, current smoking, excessive alcohol use, chronic corticosteroid use, history of prior fractures, history of falls, history of hypogonadism, history of stroke, and history of diabetes. Statistical heterogeneity of the meta-analytic estimates of all associations was significant except for chronic corticosteroid use. None of these associations were of large magnitude (i.e. adjusted odds ratios were generally <2). No evidence supporting a particular effective testing or screening strategy was identified. CONCLUSIONS: Multiple risk factors for fractures in men were identified, but their usefulness for stratifying and selecting men for bone density testing remains uncertain.

Influence of age on the association of retinol-binding protein 4 with metabolic syndrome.

OBJECTIVE: The relationships of retinol-binding protein 4 (RBP4) with insulin sensitivity and body fat distribution have been investigated in a few recent studies with conflicting results. This may have been due to differences in ages of the subjects in the different studies. The aim of this study was to investigate whether the association of RBP4 and insulin sensitivity and percent trunk fat are influenced by age. METHODS AND PROCEDURES: Cross-sectional analyses of 48 young subjects and 55 elderly subjects. Insulin sensitivity was determined by a hyperinsulinemic-euglycemic clamp. Body fat distribution was determined by a dual-energy X-ray absorptiometry (DXA). RESULTS: In the young subjects, RBP4 levels were associated with insulin sensitivity (r = -0.30, P = 0.04), percent trunk fat (r = 0.54, P < 0.001), triglycerides (r = 0.44, P = 0.003), low-density lipoprotein (r = 0.38, P = 0.01). In contrast, in the elderly subjects there was no correlation between RBP4 levels and insulin sensitivity (r = -0.18, P = 0.20), percent trunk fat (r = 0.00, P = 0.10), triglycerides (r = 0.25, P = 0.10), and low-density lipoprotein (r = -0.11, P = 0.47). DISCUSSION: The associations of RBP4 with insulin sensitivity, percent trunk fat, and lipid levels are influenced by age.

Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes.

BACKGROUND: Adipose tissue is responsible for releasing various adipokines that have been related to insulin resistance. Understanding the relationship of these adipokines to insulin resistance may foster the development of new treatments for diabetes. OBJECTIVES: The primary objective of this study was to determine whether an association between retinol-binding protein 4 (RBP4) and insulin resistance exists in nonobese individuals without a family history or diagnosis of diabetes. The secondary objective was to determine by a dual energy x-ray absorptiometry scan which adipose tissue depot most closely relates to RBP4 levels. DESIGN: Cross-sectional analysis of 92 study participants ranging in age from 20 to 83 yr was performed. The range of body mass index (BMI) was from 18 to 30 kg/m(2). Exclusion criteria were a BMI greater than 30 kg/m(2), family history of diabetes, or a diagnosis of diabetes. Insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp. Body fat was measured by dual energy x-ray absorptiometry scan. RESULTS: RBP4 values were lower in females (35.8 +/- 1.7 microg/ml) compared with males (39.9 +/- 1.4 microg/ml; P = 0.06). RBP4 levels were found to correlate negatively with insulin sensitivity (r = -0.32; P = 0.002) and positively with age (r = 0.38; P < 0.001). RBP4 levels did not correlate with BMI (r = -0.13; P = 0.22), trunk fat (r = 0.16; P = 0.22), or percent body fat (r = 0.07; P = 0.65). However, RBP4 levels did correlate with percent trunk fat (r = 0.36; P = 0.001). CONCLUSION: These findings indicate a relationship between RBP4, insulin sensitivity, and percent trunk fat in individuals who may not have features of insulin resistance.