The Periodontitis and Vascular Events (PAVE) pilot study: adverse events

BACKGROUND: During the last 15 years, a substantial number of population-based, clinical, laboratory, and animal studies have been published that reported findings on the relationship between periodontal disease and cardiovascular disease. The Periodontitis and Vascular Events (PAVE) pilot study was conducted to investigate the feasibility of a randomized secondary prevention trial to test whether treatment of periodontal disease reduces the risk for cardiovascular disease. This article describes the occurrence of adverse events during the pilot study. METHODS: The PAVE pilot study was a multicenter, randomized trial comparing periodontal therapy to community dental care. Baseline and follow-up clinic visits included a periodontal examination; blood, subgingival plaque, and crevicular fluid specimen collection; and medical and dental histories. Telephone follow-up contacts were scheduled to occur 3 months after randomization and every 6 months thereafter to assess adverse events or endpoints. RESULTS: Cardiovascular adverse events occurred with similar frequency (23 versus 24 [P = 0.85] in the community control and the treatment groups, respectively). There were 15 serious adverse events (SAEs) with a non-significantly higher percentage occurring in the community care group (6.6% versus 3.3%; P = 0.19). A time-to-event analysis of patterns of SAEs indicated that subjects in the periodontal therapy group tended to be less likely to experience an SAE over the entire 25 months of the study. CONCLUSION: For those individuals who remained in the study, it appears that provision of periodontal scaling and root planing treatment to individuals with heart disease resulted in a similar pattern of adverse events as seen in the community care group, which also received some treatment.     

Homozygous mutation in ELMO2 may cause Ramon syndrome

We report on a girl, born to first cousin Lebanese parents, with intellectual disability, seizures, repeated gingivorrhagia, enlarged lower and upper jaws, overgrowth of the gums, high arched and narrow palate, crowded teeth, hirsutism of the back, large abdomen and a small umbilical hernia. Cysts of the mandible, fibrous dysplasia of bones, and enlarged adenoids causing around 60% narrowing of the nasopharyngeal airways were noted at radiographic examination. Her brother presented with the same features in addition to a short stature, an ostium secundum, and more pronounced intellectual disability. He died at the age of 8 years from a severe pulmonary infection and repeated bleeding episodes. A clinical diagnosis of Ramon syndrome was made. Whole exome sequencing studies performed on the family revealed the presence of a novel homozygous missense mutation in ELMO2 gene, p.I606S in the affected individuals. Loss of function mutations in ELMO2 have been recently described in another clinically distinct condition: primary intraosseous vascular malformation or intraosseous hemangioma, called VMOS. Review of the literature and differential diagnoses are discussed.     

Factor Structure and Validity of a Revised Pain Anxiety Symptom Scale

The Pain Anxiety Symptoms Scale (PASS) (McCracken et al., 1992) is a frequently used 40-item measure designed to assess fearful appraisals of pain, pain-related cognitive and physiological anxiety, and escape/avoidance behavior. Research has shown the PASS to possess a reasonable validity; however, recent evidence has raised questions regarding the factorial validity of its subscales and indicates that revision and expansion appear warranted. Accordingly, we developed a revised and expanded Pain Anxiety Symptoms Scale (PASS-R). In Study 1, we expanded the item pool and administered the questions to a sample of 69 university students. On the basis of expert opinion and item analysis, we retained a total of 72 items. In Study 2, we subjected the responses of 256 university students to the 72-item PASS-R to a principal-components analysis with oblique rotation. This analysis revealed five lower-order factors (Interference, Approach Behaviours, Catastrophic Thoughts, Monitoring and Prevention, and Physiological Arousal) that loaded together on a single higher-order factor. We created new subscales on the basis of the lower-order factor structure and compared these subscales to a number of other self-report measures of pain, pain behavior, and related psychopathology. The PASS-R subscales demonstrated a good to excellent internal consistency as well as a good construct and criterion validity and contributed unique variance to the prediction of behavioral reactions to recent pain experiences (e.g., visiting a physician). Collectively, these results suggest that the PASS-R is a psychometrically sound self-report measure that allows detailed assessment of anxiety-related cognitions, physiological arousal, and behaviors in response to pain. The paper concludes with a discussion of implications of the studies and future research directions.     

EphB4 enhances the process of endochondral ossification and inhibits remodeling during bone fracture repair

Previous reports have identified a role for the tyrosine kinase receptor EphB4 and its ligand, ephrinB2, as potential mediators of both bone formation by osteoblasts and bone resorption by osteoclasts. In the present study, we examined the role of EphB4 during bone repair after traumatic injury. We performed femoral fractures with internal fixation in transgenic mice that overexpress EphB4 under the collagen type 1 promoter (Col1‐EphB4) and investigated the bone repair process up to 12 weeks postfracture. The data indicated that Col1‐EphB4 mice exhibited stiffer and stronger bones after fracture compared with wild‐type mice. The fractured bones of Col1‐EphB4 transgenic mice displayed significantly greater tissue and bone volume 2 weeks postfracture compared with that of wild‐type mice. These findings correlated with increased chondrogenesis and mineral formation within the callus site at 2 weeks postfracture, as demonstrated by increased safranin O and von Kossa staining, respectively. Interestingly, Col1‐EphB4 mice were found to possess significantly greater numbers of clonogenic mesenchymal stromal progenitor cells (CFU‐F), with an increased capacity to form mineralized nodules in vitro under osteogenic conditions, when compared with those of the wild‐type control mice. Furthermore, Col1‐EphB4 mice had significantly lower numbers of TRAP‐positive multinucleated osteoclasts within the callus site. Taken together, these observations suggest that EphB4 promotes endochondral ossification while inhibiting osteoclast development during callus formation and may represent a novel drug target for the repair of fractured bones. © 2013 American Society for Bone and Mineral Research.     

Practicality, safety and accuracy of computed tomography coronary angiography in the evaluation of low TIMI-risk score chest pain patients: a pilot study

Objectives: The present pilot study aimed to assess the practicality, safety and accuracy of performing CT coronary angiography (CT‐CA) in the evaluation of acute chest pain of patients with low thrombolysis in myocardial infarction (TIMI) risk scores. Methods: The present prospective observational study was undertaken in a university teaching hospital between November 2004 and December 2005. Participants were a convenience sample of patients admitted to hospital for investigation of chest pain with TIMI risk scores <3. Consenting patients underwent CT‐CA within 48 h of presentation. Outcomes of interest were practicality (proportion of diagnostic quality scans obtained and preparation time for CT‐CA), rate of serious adverse events, and accuracy at the patient level using selective coronary angiography as the reference standard. Results: Thirty‐four patients were recruited. Diagnostic quality scans were obtained in 26/34 or 76% of patients (four failed CT‐CA and four non‐diagnostic scans). The median CT preparation time was 1.9 h (range 0.17–4.0). No serious adverse events were found. Fourteen of those 26 patients with diagnostic CT‐CA subsequently had selective coronary angiography, of which nine were positive. The sensitivity and specificity of CT‐CA in identifying patients with significant coronary artery disease were 9/9 (100%; 95% confidence interval 72–100%) and 4/5 (80%; 95% confidence interval 28–100%), respectively. Conclusions: The majority of acute chest pain patients with low TIMI risk scores were successfully scanned with a 16‐slice CT to produce CT‐CA studies with good diagnostic quality and accuracy. No major adverse events were found. The place of CT‐CA in diagnostic workup for chest pain remains to be defined.     

Frequency and temporal profile of poststroke hyperglycemia using continuous glucose monitoring

OBJECTIVE: Poststroke hyperglycemia (PSH) is common and has adverse effects on outcome. In this observational study, we aimed to describe the frequency and temporal profile of PSH using a continuous glucose monitoring system (CGMS) in patients with and without diabetes. RESEARCH DESIGN AND METHODS: Fifty-nine patients with acute hemispheric ischemic stroke were prospectively studied with the CGMS, regardless of medication, admission plasma glucose value, and diabetes status. The CGMS records interstitial glucose every 5 min for 72 h. RESULTS: On admission, 36% of patients had preexisting diabetes. At the earliest analyzed time point of 8 h from stroke onset, 50% of nondiabetic subjects and 100% of diabetic patients were hyperglycemic (> or =7 mmol/l). This early-phase hyperglycemia was followed by a decrease in glucose 14-16 h poststroke when only 11% of nondiabetic and 27% of diabetic patients were hyperglycemic. A late hyperglycemic phase 48-88 h poststroke was observed in 27% of nondiabetic and 78% of diabetic patients. Thirty-four percent of nondiabetic and 86% of diabetic patients were hyperglycemic for at least a quarter of the monitoring period. Multivariate regression analysis demonstrated that diabetes, insular cortical ischemia, and increasing age independently predicted higher glucose values. CONCLUSIONS: Poststroke hyperglycemia is common and prolonged despite treatment based on current guidelines. There are early and late hyperglycemic phases in nondiabetic as well as diabetic patients. Treatment protocols with frequent glucose measurement and intensive glucose-lowering therapy for a minimum of 72 h poststroke need to be evaluated.