Comparison of a Chronotherapeutically Administered β Blocker vs. a Traditionally Administered β Blocker in Patients With Hypertension

Increasing systolic blood pressure and heart rate during the early morning results in increased myocardial oxygen demand. The use of β blockers during this period may decrease cardiac workload, particularly in β-blocker sensitive patients. The impact of a new chronotherapeutic β blocker was assessed in 44 hypertensive patients. Patients were randomized to delayed-release propranolol (INP) dosed at 10 p.m. or to traditionally dosed propranolol (ILA) dosed at 8 a.m. for 4 weeks, following which they were switched to the alternative formulation for 4 weeks. Thirty-four-hour ambulatory blood pressure monitoring and pharmacokinetic measurements were obtained. INP and ILA resulted in significant reductions in mean 24-hour blood pressure (−9.01-6.9 mm Hg and −10.41-7.7 mm Hg, respectively). The top 25% of responders to highdose propranolol (sensitive patients) were compared on each formulation. Mean trough reductions were −8.0/-6.7 mm Hg and −7.61-5.8 mm Hg, respectively. Mean blood pressure reductions in the β-blocker sensitive patients (n=11) between 6 a.m. and noon were −15.2/-11.9 mm Hg on INP and -8.0/-4.6 mm Hg on ILA. Heart rate reduction was −14.1 bpm and double product reduction was −3319 in the INP patients between 6 a.m. and 12 noon compared with −10.5 and −2209 in the ILA patients. This study suggests that INP and ILA are effective once-a-day β blockers, but the use of delayed-release propanolol results in a greater reduction in double product between 6 a.m. and noon in β-blocker sensitive patients than does traditionally dosed propranolol.     

Diagnosing osteoporosis by using dental panoramic radiographs: the OSTEODENT project.

OBJECTIVES: Measurement of cortical thickness and subjective assessment of cortical porosity on panoramic radiographs are methods previously reported for diagnosing osteoporosis. The aims of this study were to determine the relative efficacy of the mandibular cortical index and cortical width in detecting osteoporosis, both alone and in combination, and to determine the optimal cortical width threshold for referral for additional osteoporosis investigation. STUDY DESIGN: Six hundred seventy-one postmenopausal women 45 to 70 years of age were recruited for this study. They received dual energy x-ray absorptiometry (DXA) scans of the left hip and lumbar spine (L1 to L4), and dental panoramic radiographic examinations of the teeth and jaws. Three observers separately assessed the mandibular cortical width and porosity in the mental foramen region of the mandible. Cortical width was corrected for magnification errors. Chi-squared automatic interaction detection analysis (CHAID) software was used (SPSS AnswerTree, version 3.1, SPSS Inc., Chicago, IL). RESULTS: Chi-squared automatic interaction detection analysis showed that the cortical porosity was a poorer predictor of osteoporosis than mandibular cortical width. For the 3 observers, a mandibular cortical width of <3 mm provided diagnostic odds ratios of 6.51, 6.09, and 8.04. The test is therefore only recommended in triage screening of individuals by using radiographs made for purposes other than osteoporosis. CONCLUSION: When evaluating panoramic radiographs, only those patients with the thinnest mandibular cortices (i.e., <3 mm) should be referred for further osteoporosis investigation.     

Self-regulation as a mediator of the effects of childhood traumatic brain injury on social and behavioral functioning.

This study builds on our earlier investigation (see Ganesalingam et al., 2006). We showed previously that children with moderate to severe traumatic brain injuries (TBI) had poorer self-regulation and social and behavioral functioning than their uninjured peers and that self-regulation predicted significant variance in parent- and teacher-rated social and behavioral outcomes, regardless of the presence or absence of TBI. In this study, we examine self-regulation as a mediator of the relationship between TBI and the outcomes. Participants included 65 children with moderate to severe TBI and 65 children without TBI matched for age and gender. Participants were between 6 and 11 years of age. Children completed an assessment of cognitive, emotional, and behavioral self-regulation, and social and behavioral functioning. Mediation was assessed using a bootstrapping approach (a relatively novel statistical method for assessing specific indirect effects in models with multiple mediators). Analyses indicated that, after controlling for socioeconomic status (SES), aspects of self-regulation accounted for individual variation in the outcomes, and acted as a significant mediator of the effects of TBI on the outcomes. Self-regulatory deficits may reflect the relative vulnerability of the prefrontal cortex to TBI and may help account for post-injury difficulties in social and behavioral functioning.     

The Hyperplantarflexion Ankle Fracture Variant

Various patterns of ankle fractures that are not accounted for by common classification systems have been the subject of case reports. The first difficulty with these variant patterns is recognizing all associated pathology, followed by the successful application of stable fixation. The purpose of this study was to describe the common morphologic features and ligamentous injuries of a unique variant fracture pattern, as well as the surgical treatment technique and the short-term functional and radiographic outcomes. Of 121 consecutive unstable ankle fractures over a 2-year period, 7 patients were found to have a similar constellation of injuries around the ankle. A vertical shear fracture of the posteromedial tibial rim was the main feature. Six of the 7 also had a fracture of the posterior malleolus. On magnetic resonance imaging, the deltoid and posterior tibiofibular ligaments were intact in all cases. Fractures were treated with open anatomic reduction of the posteromedial and posterior fragments with antiglide plate fixation. All fractures healed at 2 months without loss of reduction, fixation failure, or surgical complications. The average American Academy of Orthopaedic Surgeons lower extremity score was 79 at an average of 8 months' follow-up. The common radiographic and morphologic features associated with this posteromedial fracture indicate that it likely occurs through a common mechanism that involves hyperplantarflexion. The characteristics of this fracture pattern have not been fully described previously, but this ankle fracture variant may occur in up to 6% of cases. Unstable ankle fractures should be evaluated carefully for evidence of posteromedial involvement so appropriate treatment may proceed.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration

OBJECTIVE: The aim was to establish the potential efficacy, tolerabilityand side-effect profile of electromagnetic therapy as an adjunctto conventional dressings in the treatment of venous leg ulcers. METHOD: A prospective, randomized, double blind controlled clinicaltrial was carried out in a dedicated leg ulcer clinic basedin one urban general practice. Nineteen patients with leg ulcersof confirmed venous aetiology were assessed. The main outcomemeasures were rate and scale of venous leg ulcer healing, changesin patient-reported pain levels, quality of life, degree ofmobility, side effect profile and acceptability to patientsand staff. RESULTS: Sixty-eight per cent of patients attending this dedicated clinicachieved improvements in the size of their ulcer (4, 21%, healedfully) and in reduced pain levels (P < 0.05) during the trial,despite the chronicity of ulcer histories. Patients treatedwith electromagnetic therapy at 800 Hz were found at day 50to have significantly greater healing (P < 0.05) and paincontrol (P < 0.05) than placebo therapy or treatment with600 Hz. All patients reported improved mobility at the end ofthe study. The electromagnetic therapy was well tolerated bypatients, with no differences between groups in reporting adverseevents, and proved acceptable to staff. CONCLUSION: Despite the small numbers in this pilot study, electromagnetictherapy provided significant gains in the healing of venousleg ulcers and reduction in pain. Keywords. Electromagnetic therapy, RCT, leg ulcers, primary care.