Research Spotlight

Gomez-Hoyos, J., R. Schroder, M. Reddy, I. J. Palmer and H. D. Martin (2016). “Femoral Neck Anteversion and Lesser Trochanteric Retroversion in Patients With Ischiofemoral Impingement: A Case-Control Magnetic Resonance Imaging Study.” Arthroscopy 32(1): 13-18.

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PURPOSE: To assess the relationship between the femoral neck version (FNV) and lesser trochanteric version (LTV) in symptomatic patients with ischiofemoral impingement (IFI) as compared with asymptomatic hips. METHODS: The FNV and LTV of patients with symptomatic IFI who underwent magnetic resonance imaging assessment including a standardized femoral version study protocol were compared with those of patients with asymptomatic hips in this retrospective, observational study. Patients with isolated intra-articular pathology, prior hip fracture, and lesser trochanter deformity were excluded. The FNV, LTV, ischiofemoral space, and quadratus femoris space were evaluated on axial magnetic resonance imaging, as well as the angle between the LTV and the FNV. Independent t-tests were used to determine differences between groups. RESULTS: Data from 11 out 15 symptomatic patients and 250 out of 320 asymptomatic patients were analyzed. The mean ischiofemoral space (11.9 v 22.9 mm; P < .001; 95% confidence interval [CI], 6.9 to 15.2) and mean quadratus femoris space (7.2 mm v 14.9 mm; P < .001; 95% CI, 5.4 to 8.6) were significantly smaller in symptomatic patients versus asymptomatic patients. There was no difference in mean LTV between groups (-23.6 degrees v -24.2 degrees ; P = .8; 95% CI, -7.5 to 6.4), however, the mean FNV (21.7 degrees v 14.1 degrees ; P = .02; 95% CI, -14.2 to -1.1) and the angle between the FNV and LTV on average (45.4 degrees v 38.3 degrees ; P = .01; 95% CI, -12.9 to -1.3) were higher in symptomatic than in asymptomatic patients, with statistical significance. CONCLUSIONS: The femoral mean neck anteversion and the mean angle between the FNV and LTV are significantly higher in patients with symptomatic IFI. The mean LTV is not increased in patients with symptomatic ischiofemoral impingement as compared with those patients with asymptomatic hips. LEVEL OF EVIDENCE: Level III, diagnostic study.

Hwang, M. H., J. K. Yoo, M. Luttrell, H. K. Kim, T. H. Meade, M. English, S. Talcott, I. Z. Jaffe and D. D. Christou (2016). “Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.” Exp Gerontol 73: 86-94.

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Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61+/-1years; mean+/-SE, 53-79years) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4mg) following eplerenone (100mg/dose, 2 doses, 24h between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9+/-0.5 to 5.6+/-0.6%, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOS(Ser1177) to total eNOS (1.53+/-0.08 vs. 1.29+/-0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9+/-1.9 vs. 21.0+/-1.5%, P=0.5 and systolic/diastolic blood pressure: 135/77+/-4/2 vs. 134/77+/-4/2mmHg, P>/=0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure.

Ilag, L. L., M. A. Deeg, T. Costigan, P. Hollander, T. C. Blevins, S. V. Edelman, R. J. Konrad, R. A. Ortmann, R. K. Pollom, W. J. Huster, J. S. Zielonka and M. J. Prince (2016). “Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus(R) insulin glargine in patients with type 1 or type 2 diabetes mellitus.” Diabetes Obes Metab 18(2): 159-168.

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AIMS: To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus(R) insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). METHODS: To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naive patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher’s exact test. RESULTS: No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naive subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes. CONCLUSIONS: LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.

Owen-Smith, A., C. Stewart, C. Green, B. K. Ahmedani, B. E. Waitzfelder, R. Rossom, L. A. Copeland and G. E. Simon (2016). “Adherence to common cardiovascular medications in patients with schizophrenia vs. patients without psychiatric illness.” Gen Hosp Psychiatry 38: 9-14.

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OBJECTIVE: The purpose of the study was to examine whether individuals with diagnoses of schizophrenia were differentially adherent to their statin or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) medications compared to individuals without psychiatric illness. METHOD: Using electronic medical record data across 13 Mental Health Research Network sites, individuals with diagnoses of schizophrenia or schizoaffective disorder receiving two or more medication dispensings of a statin or an ACEI/ARB in 2011 (N=710) were identified and matched on age, sex and Medicare status to controls with no documented mental illness and two or more medication dispensings of a statin in 2011 (N=710). Medication adherence, and sociodemographic and clinical characteristics of the study population were assessed. RESULTS: Multivariable models indicated that having a schizophrenia diagnosis was associated with increased odds of statin medication adherence; the odds ratio suggested a small effect. After adjustment for medication regimen, schizophrenia no longer showed an association with statin adherence. Having a schizophrenia diagnosis was not associated with ACEI/ARB medication adherence. CONCLUSIONS: Compared to patients without any psychiatric illness, individuals with schizophrenia were marginally more likely to be adherent to their statin medications. Given that patterns of adherence to cardioprotective medications may be different from patterns of adherence to antipsychotic medications, improving adherence to the former may require unique intervention strategies.

Scherrer, J. F., J. Salas, L. A. Copeland, E. M. Stock, B. K. Ahmedani, M. D. Sullivan, T. Burroughs, F. D. Schneider, K. K. Bucholz and P. J. Lustman (2016). “Prescription Opioid Duration, Dose, and Increased Risk of Depression in 3 Large Patient Populations.” Ann Fam Med 14(1): 54-62.

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PURPOSE: Recent results suggests the risk of a new onset of depression increases with longer duration of opioid analgesic use. It is unclear whether new-onset depression related to opioid analgesic use is a function of the dose prescribed or the duration of use or both. METHODS: Using a retrospective cohort design, we collected patient data from 2000 to 2012 from the Veterans Health Administration (VHA), and from 2003 to 2012 from both Baylor Scott & White Health (BSWH) and the Henry Ford Health System (HFHS). Patients (70,997 VHA patients, 13,777 BSWH patients, and 22,981 HFHS patients) were new opioid users, aged 18 to 80 years, without a diagnosis of depression at baseline. Opioid analgesic use duration was defined as 1 to 30, 31 to 90, and more than 90 days, and morphine equivalent dose (MED) was defined as 1 to 50 mg/d, 51 to 100 mg/d, and greater than 100 mg/d of analgesic. Pain and other potential confounders were controlled for by inverse probability of treatment-weighted propensity scores. RESULTS: New-onset depression after opioid analgesic use occurred in 12% of the VHA sample, 9% of the BSWH sample, and 11% of the HFHS sample. Compared with 1- to 30-day users, new-onset depression increased in those with longer opioid analgesic use. Risk of new-onset depression with 31 to 90 days of opioid analgesic use ranged from hazard ratio [HR] = 1.18 (95% CI, 1.10-1.25) in VHA to HR = 1.33 (95% CI, 1.16-1.52) in HFHS; in opioid analgesic use of more than 90 days, it ranged from HR = 1.35 (95% CI, 1.26-1.44) in VHA to HR = 2.05 (95% CI, 1.75-2.40) in HFHS. Dose was not significantly associated with a new onset of depression. CONCLUSIONS: Opioid-related new onset of depression is associated with longer duration of use but not dose. Patients and practitioners should be aware that opioid analgesic use of longer than 30 days imposes risk of new-onset depression. Opioid analgesic use, not just pain, should be considered a potential source when patients report depressed mood.