Summary Background Addition of a sulphonylurea to metformin improves glycaemic control in type 2 diabetes, but is associated with hypoglycaemia and weight gain. We aimed to compare a dipeptidyl ...peptidase-4 inhibitor (linagliptin) against a commonly used sulphonylurea (glimepiride). Methods In this 2-year, parallel-group, non-inferiority double-blind trial, outpatients with type 2 diabetes and glycated haemoglobin A1c (HbA1c ) 6·5–10·0% on stable metformin alone or with one additional oral antidiabetic drug (washed out during screening) were randomly assigned (1:1) by computer-generated random sequence via a voice or web response system to linagliptin (5 mg) or glimepiride (1–4 mg) orally once daily. Study investigators and participants were masked to treatment assignment. The primary endpoint was change in HbA1c from baseline to week 104. Analyses included all patients randomly assigned to treatment groups who received at least one dose of treatment, had a baseline HbA1c measurement, and had at least one on-treatment HbA1c measurement. This trial is registered at ClinicalTrials.gov , number NCT00622284. Findings 777 patients were randomly assigned to linagliptin and 775 to glimepiride; 764 and 755 were included in analysis of the primary endpoint. Reductions in adjusted mean HbA1c (baseline 7·69% SE 0·03 in both groups) were similar in the linagliptin (–0·16% SE 0·03) and glimepiride groups (–0·36% 0·03; difference 0·20%, 97·5% CI 0·09–0·30), meeting the predefined non-inferiority criterion of 0·35%. Fewer participants had hypoglycaemia (58 7% of 776 vs 280 36% of 775 patients, p<0·0001) or severe hypoglycaemia (1 <1% vs 12 2%) with linagliptin compared with glimepiride. Linagliptin was associated with significantly fewer cardiovascular events (12 vs 26 patients; relative risk 0·46, 95% CI 0·23–0·91, p=0·0213). Interpretation The results of this long-term randomised active-controlled trial advance the clinical evidence and comparative effectiveness bases for treatment options available to patients with type 2 diabetes mellitus. The findings could improve decision making for clinical treatment when metformin alone is insufficient. Funding Boehringer Ingelheim.
Background Anhedonia has long been recognized as a key feature of major depressive disorders, but little is known about the association between hedonic symptoms and neurobiological processes in ...depressed patients. We investigated whether amygdala mood-congruent responses to emotional stimuli in depressed patients are correlated with anhedonic symptoms at automatic levels of processing. Methods We measured amygdala responsiveness to subliminally presented sad and happy facial expressions in depressed patients and matched healthy controls using functional magnetic resonance imaging. Amygdala responsiveness was compared between patients and healthy controls within a 2 (group) × 2 (emotion) design. In addition, we correlated patients’ amygdala responsiveness to sad and happy facial stimuli with self-report questionnaire measures of anhedonia. Results We included 35 patients and 35 controls in our study. As in previous studies, we observed a strong emotion × group interaction in the bilateral amygdala: depressed patients showed greater amygdala responses to sad than happy faces, whereas healthy controls responded more strongly to happy than sad faces. The lack of automatic right amygdala responsiveness to happy faces in depressed patients was associated with higher physical anhedonia scores. Limitations Almost all depressed patients were taking antidepressant medications. Conclusion We replicated our previous finding of depressed patients showing automatic amygdala mood-congruent biases in terms of enhanced reactivity to negative emotional stimuli and reduced activity to positive emotional stimuli. The altered amygdala processing of positive stimuli in patients was associated with anhedonia scores. The results indicate that reduced amygdala responsiveness to positive stimuli may contribute to an-hedonic symptoms due to reduced/inappropriate salience attribution to positive information at very early processing levels.
Trauma history and increased exposure to combat and sexual trauma may account for heightened rates of PTSD among military populations. This study assessed trauma type and exposure history, diagnostic ...impressions, and PTSD severity in a large clinical dataset (n = 2463) of veterans presenting for PTSD evaluation at a Midwestern VA Medical Center between the years 2006 and 2013. The degree of lifetime trauma exposure was pronounced, with approximately 76% of the sample reporting exposure to at least four traumatic events. Higher numbers of lifetime trauma and higher levels of combat exposure were associated with more severe PTSD symptoms. Sexual trauma and combat trauma were more predictive of PTSD than other trauma types. Sexual trauma was associated with more severe PTSD than combat and other trauma.
Study objective We ascertain the components of emergency department (ED) length of stay for adult patients receiving psychiatric evaluation and to examine their variability across 5 hospitals within ...a health care system. Methods This was a prospective study of 1,092 adults treated between June 2008 and May 2009. Research staff abstracted length of stay and clinical information from the medical records. Clinicians completed a time log for each patient contact. Main outcomes were median times for the overall ED length of stay and its 4 components, or time from triage to request for psychiatric evaluation, request to start of psychiatric evaluation, start to completion of psychiatric evaluation with a disposition decision, and disposition decision to discharge from the ED. Results The overall median length of stay was more than 8 hours. Median times for the components were 1.8 hours from triage to request, 15 minutes from request to start of psychiatric evaluation, 75 minutes from start of psychiatric evaluation to disposition decision, and nearly 3 hours from disposition decision to ED discharge. The median disposition decision to discharge time was substantially shorter for patients who went home (40 minutes) than for patients who were admitted (2.5 hours) or transferred for psychiatric admission at other facilities (6.3 hours). When adjustments for patient and clinical factors were made, differences in ED length of stay persisted between hospitals. Conclusion ED length of stay for psychiatric patients varied greatly between hospitals, highlighting differences in the organization of psychiatric services and inpatient bed availability. Findings may not generalize to other settings or populations.
Summary Background Use of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has the potential to increase survival in patients with advanced non-small-cell lung ...cancer. We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer. Methods In a multinational, multicentre, open-label, phase III trial, chemotherapy-naive patients (≥18 years) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy. Chemotherapy was cisplatin 80 mg/m2 intravenous infusion on day 1, and vinorelbine 25 mg/m2 intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles. Cetuximab—at a starting dose of 400 mg/m2 intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m2 over 1 h per week—was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred. The primary endpoint was overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00148798. Findings Between October, 2004, and January, 2006, 1125 patients were randomly assigned to chemotherapy plus cetuximab (n=557) or chemotherapy alone (n=568). Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group (median 11·3 months vs 10·1 months; hazard ratio for death 0·871 95% CI 0·762–0·996; p=0·044). The main cetuximab-related adverse event was acne-like rash (57 10% of 548, grade 3). Interpretation Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer. Funding Merck KGaA.
The high coronary artery disease (CAD) prevalence in patients with abdominal aortic aneurysm (AAA) is well known. However, the inverse relation has been little explored. We present, based on a ...systematic review and meta-analysis of the published evidence, a critical appraisal of the issue of AAA prevalence and also AAA predictive risk factors in patients with CAD, comparing it with AAA prevalence in subjects without CAD. A total of 22 studies involving 13,388 patients with CAD met the inclusion criteria. Overall, AAA prevalence in patients with CAD was 8.4% (95% confidence interval CI 6.9 to 10.3), significantly higher than in subjects without CAD (odds ratio OR 2.42, 95% CI 2.08 to 2.81). Pooled analysis revealed that smoking, arterial hypertension, and concomitant carotid artery stenosis were significantly associated with AAA in patients with CAD (OR 1.72, 95% CI 1.14 to 2.61; OR 1.57, 95% CI 1.06 to 2.35; OR 2.14, 95% CI 1.20 to 3.79, respectively). In patients with CAD, AAA prevalence tended to be higher with concomitant peripheral artery disease (OR 2.66, 95% CI 0.82 to 8.61, p = 0.08). In conclusion, AAA prevalence was significantly higher in patients with CAD versus subjects without CAD.
Experimental results are presented on single-bit-upsets (SBU) and multiple-bit-upsets (MBU) on a 45 nm SOI SRAM. The accelerated testing results show the SBU-per-bit cross section is relatively ...constant with technology scaling but the MBU cross section is increasing. The MBU data show the importance of acquiring and analyzing the data with respect to the location of the multiple-bit upsets since the relative location of the cells is important in determining which MBU upsets can be corrected with error correcting code (ECC) circuits. For the SOI SRAMs, a large MBU orientation effect is observed with most of the MBU events occurring along the same SRAM bit-line; allowing ECC circuits to correct most of these MBU events.
To determine the functional outcomes associated with long-term multidisciplinary treatment, intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation in children with severe ...osteogenesis imperfecta (OI) (diagnosed clinically as OI types III or IV).
Retrospective study where outcomes were measured prospectively.
Pediatric orthopedic hospital.
Adolescents (N=41; age range, 15-21y) with severe OI (OI type III: n=17; OI type IV: n=24) who had started therapy before the age of 6 years, had received treatment for at least 10 years, and had achieved final height.
Intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation.
Pediatric Evaluation of Disability Inventory.
At the time of the last available follow-up examination, none of the individuals diagnosed with OI type III (most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV were able to ambulate without ambulation aids. Regarding self-care, we specifically assessed 8 skills that we deemed essential for living independently (grooming; dressing; toileting; bed, chair, toilet, tub, and car transfers). Only 6 (35%) of the youths with OI type III were able to complete all 8 items, whereas 23 (96%) individuals with OI type IV managed to perform all tasks. Teens with OI type III often needed assistance for the transfer to toilet, tub, and car and for personal hygiene and clothing management associated with toileting, usually because of limitations in upper-extremity function.
These observations suggest that further improvements in the functional status of the most severely affected children with OI are contingent on advances in the clinical management of upper-extremity issues.
Objective To use peripheral quantitative computed tomography to determine the cross-sectional area (CSA) of subcutaneous fat and muscle (fat CSA, muscle CSA) in transverse forearm scans in patients ...with osteogenesis imperfecta (OI). Study design Fat and muscle CSA were quantified in 266 individuals (142 female) aged 5-20 years who had a diagnosis of OI type I, III, or IV and who had mutations in COL1A1 or COL1A2 . Results were compared with those of 255 healthy controls. Results In a subgroup of 39 patients with OI type I, % fat CSA correlated closely with total body percentage fat mass as determined by dual-energy x-ray absorptiometry (R2 = 0.69; P < .001). In the entire study cohort, muscle CSA adjusted for age, sex, and forearm length was lower in OI type I and III than in controls ( P < .05 each), but fat CSA was similar between OI types and controls. No relationship between the type of disease-causing mutation in the COL1A1 or COL1A2 genes and fat CSA or muscle CSA was found. Conclusions Children and adolescents with OI have low muscle size but a normal amount of subcutaneous fat at the forearm.
PDF
