Ultrasound-mediated transdermal transport of insulin in vitro through human skin using novel transducer designs

Recent studies have shown that ultrasound (US)-mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to improve low-frequency (20 kHz) US methods for enhancing the transport of insulin in vitro across human skin. The feasibility of using US produced by small, lightweight novel transducers was explored for enhancing the transport of insulin across skin. Previous investigators have used US devices such as large, heavy sonicators or commercially obtained transducers for this type of research. The experiments carried out in this study used two low-profile novel US transducer arrays, the stack and standard array, for improved transport of insulin. The stack array generated a spatial peak temporal peak intensity (I(SPTP)) of 15.4 +/- 0.6 mW/cm(2) and the standard array had an I(SPTP) of 173.7 +/- 1.2 mW/cm(2). Spectrophotometeric absorption techniques were used for determining insulin transport in vitro across human skin. Compared with passive transmission (4.1 +/- 0.5 U) over an exposure period of 1 h, the standard array facilitated over a sevenfold increase in the noninvasive transdermal transport of Humulin R insulin (45.9 +/- 12.9 U). Using Humalog insulin with the standard array, there was a fourfold increase in the US-facilitated transmission over that in the control. These promising results indicate that low-frequency US can be used in a practical device for enhanced transport across the stratum corneum.     

Higher order aberrations,refractive error development and myopia control: a review

Evidence from animal and human studies suggests that ocular growth is influenced by visual experience. Reduced retinal image quality and imposed optical defocus result in predictable changes in axial eye growth. Higher order aberrations are optical imperfections of the eye that alter retinal image quality despite optimal correction of spherical defocus and astigmatism. Since higher order aberrations reduce retinal image quality and produce variations in optical vergence across the entrance pupil of the eye, they may provide optical signals that contribute to the regulation and modulation of eye growth and refractive error development. The magnitude and type of higher order aberrations vary with age, refractive error, and during near work and accommodation. Furthermore, distinctive changes in higher order aberrations occur with various myopia control treatments, including atropine, near addition spectacle lenses, orthokeratology and soft multifocal and dual-focus contact lenses. Several plausible mechanisms have been proposed by which higher order aberrations may influence axial eye growth, the development of refractive error, and the treatment effect of myopia control interventions. Future studies of higher order aberrations, particularly during childhood, accommodation, and treatment with myopia control interventions are required to further our understanding of their potential role in refractive error development and eye growth.     

Orofacial neuralgia associated with a middle cerebral artery aneurysm

Chronic orofacial pain of neuropathic origin can present diagnostic and management dilemmas to dental practitioners and also affects the patient's quality of life. Intracranial aneurysms are a potential cause of stroke (e.g. sub‐arachnoid haemorrhage) that is usually associated with, high rates of mortality and morbidity. A patient who had been previously managed for symptoms of temporomandibular joint disorder (TMD) presented with sharp, shooting pain of moderate intensity. It was precipitated by swallowing, and radiated to the right throat, posterior border of the mandible, ear and temporomandibular joint. Clinical and radiological investigations ruled out odontogenic pain, TMD and other more common types of facial pain. Magnetic resonance imaging revealed a 7 × 6 mm aneurysm in the right middle cerebral artery (MCA) which was subsequently surgically clipped. Interestingly, the facial pain resolved after this procedure. Compression of the insular region of the brain innervated by the trigeminal, glossopharyngeal and vagus nerves provides a plausible explanation for the pain reported. To our knowledge, this is the first case of facial neuralgia associated with an aneurysm in the MCA which emphasizes the importance of a multidisciplinary approach in the diagnosis and management of unusual cases of chronic orofacial pain.     

Economic Evaluation of a Web-Based Tailored Lifestyle Intervention for Adults: Findings Regarding Cost-Effectiveness and Cost-Utility From a Randomized Controlled Trial

Background

Different studies have reported the effectiveness of Web-based computer-tailored lifestyle interventions, but economic evaluations of these interventions are scarce.

Objective

The objective was to assess the cost-effectiveness and cost-utility of a sequential and a simultaneous Web-based computer-tailored lifestyle intervention for adults compared to a control group.

Methods

The economic evaluation, conducted from a societal perspective, was part of a 2-year randomized controlled trial including 3 study groups. All groups received personalized health risk appraisals based on the guidelines for physical activity, fruit intake, vegetable intake, alcohol consumption, and smoking. Additionally, respondents in the sequential condition received personal advice about one lifestyle behavior in the first year and a second behavior in the second year; respondents in the simultaneous condition received personal advice about all unhealthy behaviors in both years. During a period of 24 months, health care use, medication use, absenteeism from work, and quality of life (EQ-5D-3L) were assessed every 3 months using Web-based questionnaires. Demographics were assessed at baseline, and lifestyle behaviors were assessed at both baseline and after 24 months. Cost-effectiveness and cost-utility analyses were performed based on the outcome measures lifestyle factor (the number of guidelines respondents adhered to) and quality of life, respectively. We accounted for uncertainty by using bootstrapping techniques and sensitivity analyses.

Results

A total of 1733 respondents were included in the analyses. From a willingness to pay of €4594 per additional guideline met, the sequential intervention (n=552) was likely to be the most cost-effective, whereas from a willingness to pay of €10,850, the simultaneous intervention (n=517) was likely to be most cost-effective. The control condition (n=664) appeared to be preferred with regard to quality of life.

Conclusions

Both the sequential and the simultaneous lifestyle interventions were likely to be cost-effective when it concerned the lifestyle factor, whereas the control condition was when it concerned quality of life. However, there is no accepted cutoff point for the willingness to pay per gain in lifestyle behaviors, making it impossible to draw firm conclusions. Further economic evaluations of lifestyle interventions are needed.

Trial Registration

Dutch Trial Register NTR2168; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2168 (Archived by WebCite at http://www.webcitation.org/6MbUqttYB).     

Detecting myocardial infarction in critical illness using screening troponin measurements and ECG recordings

Introduction

To use screening cardiac troponin (cTn) measurements and electrocardiograms (ECGs) to determine the incidence of elevated cTn and of myocardial infarction (MI) in patients admitted to the intensive care unit (ICU), and to assess whether these findings influence prognosis. This is a prospective screening study.

Materials and methods

We enrolled consecutive patients admitted to a general medical-surgical ICU over two months. All patients underwent systematic screening with cTn measurements and ECGs on ICU admission, then daily for the first week in ICU, alternate days for up to one month and weekly thereafter until ICU death or discharge, for a maximum of two months. Patients without these investigations ordered during routine clinical care underwent screening for study purposes but these results were unavailable to the ICU team. After the study, all ECGs were interpreted independently in duplicate for ischaemic changes meeting ESC/ACC criteria supporting a diagnosis of MI. Patients were classified as having MI (elevated cTn and ECG evidence supporting diagnosis of MI), elevated cTn only (no ECG evidence supporting diagnosis of MI), or no cTn elevation.

Results

One hundred and three patients were admitted to the ICU on 112 occasions. Overall, 37 patients (35.9 per cent) had an MI, 15 patients (14.6 per cent) had an elevated cTn only and 51 patients (49.5 per cent) had no cTn elevation. Patients with MI had longer duration of mechanical ventilation (p < 0.0001), longer ICU stay (p = 0.001), higher ICU mortality (p < 0.0001) and higher hospital mortality (p < 0.0001) compared with those with no cTn elevation. Patients with elevated cTn had higher hospital mortality (p = 0.001) than patients without cTn elevation. Elevated cTn was associated with increased hospital mortality (odds ratio 27.3, 95 per cent CI 1.7 – 449.4), after adjusting for APACHE II score, MI and advanced life support. The ICU team diagnosed 18 patients (17.5 per cent) as having MI on clinical grounds; four of these patients did not have MI by adjudication. Thus, screening detected an additional 23 MIs not diagnosed in practice, reflecting 62.2 per cent of MIs ultimately diagnosed. Patients with MI diagnosed by the ICU team had similar outcomes to patients with MI detected by screening alone.

Conclusion

Systematic screening detected elevated cTn measurements and MI in more patients than were found in routine practice. Elevated cTn was an independent predictor of hospital mortality. Further research is needed to evaluate whether screening and subsequent treatment of these patients reduces mortality.     

Comparison of platelet-rich plasma, bovine porous bone mineral, and guided tissue regeneration versus platelet-rich plasma and bovine porous bone mineral in the treatment of intrabony defects: a reentry study

BACKGROUND: A combination of platelet-rich plasma (PRP), bovine porous bone mineral (BPBM), and guided tissue regeneration (GTR) has been shown to be effective in promoting reduction in probing depth, gain in clinical attachment, and defect fill in intrabony periodontal lesions. The individual role played by PRP, BPBM, and GTR in this combined therapy is unclear and needs to be elucidated. The purpose of this study was to compare the clinical effectiveness of 2 regenerative techniques for intrabony defects in humans: a combination of PRP/BPBM/GTR versus a combination of PRP/BPBM. METHODS: Twenty-one patients participated in the study. Using a split-mouth design, interproximal bony defects were surgically treated with either a combination of PRP/BPBM/GTR or PRP/BPBM. The primary outcomes of the study included changes in probing depth, attachment level, and defect fill as revealed by reentry surgeries at 6 months post-treatment. RESULTS: At 6 months postoperatively, clinical examination of the treated defects revealed that both treatment modalities resulted in significant probing depth reduction and clinical attachment gain compared to baseline values. Probing depth improvement was 3.98 +/- 1.02 mm on buccal and 3.94 +/- 0.94 mm on lingual sites for the PRP/BPBM group and 4.19 +/- 0.88 mm on buccal and 4.21 +/- 0.92 mm on lingual sites for the PRP/BPBM/GTR group. Gain in clinical attachment was 3.78 +/- 0.72 mm on buccal and 3.84 +/- 0.76 mm on lingual sites for the PRP/BPBM group and 4.12 +/- 0.78 mm on buccal and 4.16 +/- 0.83 mm on lingual sites for the PRP/BPBM/GTR group. Reentry surgeries revealed similar defect fill for both treatment groups (PRP/BPBM group: 4.82 +/- 1.34 mm on buccal and 4.74 +/- 1.30 mm on lingual sites; PRP/BPBM/GTR group: 4.96 +/- 1.28 mm on buccal and 4.78 +/- 1.32 mm on lingual sites). None of the differences between the 2 treatment groups was statistically significant. CONCLUSIONS: The results of this study show that both combinations of PRP/BPBM/GTR and PRP/BPBM are effective in the treatment of intrabony defects present in patients with advanced chronic periodontitis. The results also suggest that GTR adds no clinical benefit to PRP/BPBM. Further studies are necessary to assess the individual role played by PRP and BPBM in the clinical outcome achieved with their combination.     

Root resorption associated with a subepithelial connective tissue graft for root coverage: clinical and histologic report of a case

This article reports on a case of root resorption following a clinically successful root coverage procedure with a subepithelial connective tissue graft on a maxillary lateral incisor. Two years after the graft procedure was performed, the tooth was extracted in conjunction with the buccal attachment apparatus. Histologic examination of the specimen revealed signs of active resorption of the dentinal surface and bone formation in the deepest portion of the resorption cavity. Possible causative factors of the root resorption process are discussed.     

Epstein-Barr virus lymphoproliferation after bone marrow transplantation

We review 15 cases of secondary B-cell lymphoproliferative disorders that occurred among 2,475 patients who received allogeneic bone marrow transplants (BMTs) at the Fred Hutchinson Cancer Research Center (Seattle) between 1969 and 1987. The histopathologic findings in 14 of the 15 patients spanned a wide spectrum of lymphoproliferative lesions. One patient had features characteristic of angioimmunoblastic lymphadenopathy. Epstein-Barr virus (EBV) genomic sequences were identified by Southern blot analysis in each of the 13 patients evaluated. Ten of the 12 lesions evaluated originated in donor cells. In two patients, who had mixed chimerism after transplantation, the lesions originated in host cells. The combined evidence from immunoglobulin light chain staining and the analysis of immunoglobulin heavy chain gene rearrangement indicated that the lesions in most patients represented polyclonal proliferations that gave rise to clonal subpopulations. The results indicate an overall actuarial incidence of 0.6% for this complication in BMT recipients. Anti-CD3 monoclonal antibody (MoAb) treatment of acute graft-v-host disease (GVHD) and T cell depletion of the donor marrow were statistically significant risk factors, and GVHD appeared to play a contributing role, particularly in the setting of human leukocyte antigen (HLA) disparity. Two patients had no identifiable risk factors. Prophylaxis or treatment with acyclovir had no detectable effect in the patients; all but two died with uncontrolled lymphoproliferation.