New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective.

Benzodiazepines represent the first-line treatment for the acute management of epileptic seizures and status epilepticus. The emergency use of benzodiazepines must be timely, and because most seizures occur outside of the hospital environment, there is a significant need for delivery methods that are easy for nonclinical caregivers to use and administer quickly and safely. In addition, the ideal route of administration should be reliable in terms of absorption. Rectal diazepam is the only licensed formulation in the USA, whereas rectal diazepam and buccal midazolam are currently licensed in the EU. However, the sometimes unpredictable absorption with rectal and buccal administration means they are not ideal routes. Several alternative routes are currently being explored. This is a narrative review of data about delivery methods for benzodiazepines alternative to the intravenous and oral routes for the acute treatment of seizures. Unconventional delivery options such as direct delivery to the central nervous system or inhalers are reported. Data show that intranasal diazepam or midazolam and the intramuscular auto-injector for midazolam are as effective as rectal or intravenous diazepam. Head-to-head comparisons with buccal midazolam are urgently needed. In addition, the majority of trials focused on children and adolescents, and further trials in adults are warranted

Automatic radiographic quantification of hand osteoarthritis; accuracy and sensitivity to change in joint space width in a phantom and cadaver study

This is the final version of the article. Available from Springer Verlag via the DOI in this record.OBJECTIVE: To validate a newly developed quantification method that automatically detects and quantifies the joint space width (JSW) in hand radiographs. Repeatability, accuracy and sensitivity to changes in JSW were determined. The influence of joint location and joint shape on the measurements was tested. METHODS: A mechanical micrometer set-up was developed to define and adjust the true JSW in an acrylic phantom joint and in human cadaver-derived phalangeal joints. Radiographic measurements of the JSW were compared to the true JSW. Repeatability, systematic error (accuracy) and sensitivity (defined as the smallest detectable difference (SDD)) were determined. The influence of joint position on the JSW measurement was assessed by varying the location of the acrylic phantom on the X-ray detector with respect to the X-ray beam and the influence of joint shape was determined by using morphologically different human cadaver joints. RESULTS: The mean systematic error was 0.052 mm in the phantom joint and 0.210 mm in the cadaver experiment. In the phantom experiments, the repeatability was high (SDD = 0.028 mm), but differed slightly between joint locations (p = 0.046), and a change in JSW of 0.037 mm could be detected. Dependent of the joint shape in the cadaver hand, a change in JSW between 0.018 and 0.047 mm could be detected. CONCLUSIONS: The automatic quantification method is sensitive to small changes in JSW. Considering the published data of JSW decline in the normal and osteoarthritic population, the first signs of OA progression with this method can be detected within 1 or 2 years.This work was funded by the Dutch Arthritis Association (Reumafonds). The study sponsor had no involvement in study design, data collection, data analysis, or interpretation of the results

The use of digital photographs for the diagnosis of hand osteoarthritis: the AGES-Reykjavik study

<p>Abstract</p> <p>Background</p> <p>The objective of the study was to standardize a method using digital photographs to diagnose and grade hand osteoarthritis (HOA), to compare it with radiographs and clinical examination with regard to prevalence and relation to symptoms, and finally to construct a simple shortened version suitable for use in very large studies, where a global estimate may be preferable.</p> <p>Methods</p> <p>High quality photographs with standard distance and hand positioning were analysed for the presence of HOA and subsequently compared with standard radiographs and clinical examination in 381 random participants in the AGES-Reykjavik Study, a large population study. The mean age of the participants was 76 years.</p> <p>Results</p> <p>Using the photographic method, the most commonly affected joints were the second DIP joints followed by the third DIP joints and second and third PIP joints. Both interobserver (ICC = 0.83) and intraobserver reading agreements (ICC = 0.89) were acceptable. On comparison with radiography and clinical examination, aggregate scores were significantly correlated (R_s0.35-0.69), more so in females (R_s0.53-0.72) than males. Hand pain in males showed very little association with HOA findings by the three methods but all methods showed a comparable moderate association with hand pain in females. The performance of photography in predicting pain on most days for at least a month in females was comparable to that of radiography and clinical examination (AUC 0.63 <it>p </it>= 0.004). Analysis of intermittent pain yielded similar results for in the DIP and PIP joints (OR 3.2-3.3, <it>p </it>< 0.01), but for the CMC1 joints, both radiography (OR 9.0, <it>p </it>< 0.0001), and clinical examination (OR 9.8, <it>p </it>< 0.0001), had higher predictive odds ratios for pain than photography (OR 3.6, <it>p </it>< 0.0001)., A shortened, rapidly performed form of reading photographs also showed a high degree of correlation with the other methods (R_s0.56-0.82).</p> <p>Conclusion</p> <p>High quality hand photographs can be used to diagnose and grade hand osteoarthritis. The method has the advantage of being inexpensive and easy to perform. By using a slightly simplified method of reading, it appears to be highly suitable for use in large studies.</p

Avaliação antropométrica e do ângulo quadricipital na osteoartrite de joelho em mulheres obesas

A osteoartrite (OA) é uma doença articular degenerativa, caracterizada por processo inflamatório, dor e deformidades; um de seus fatores preditivos é a obesidade. O objetivo deste estudo foi verificar possíveis correlações entre medidas antropométricas, o ângulo quadricipital (Q) e a osteoartrite de joelho. A amostra foi composta por 50 voluntárias obesas (30 com OA de joelho e 20 sem OA), com idade entre 40 e 60 anos. Foram mensurados, além do IMC (índice de massa corporal), circunferência abdominal (CA), perímetros de cintura e quadril para cálculo da relação cintura-quadril e o ângulo Q; a osteoartrite foi diagnosticada clinicamente e por meio de radiografia da articulação do joelho. Foram encontradas correlações positivas fracas entre IMC e ângulo Q e entre tempo de obesidade e grau de degeneração articular. A CA apresentou correlação positiva fraca com o grau de degeneração articular e o de gravidade da OA. O cálculo da razão de chance (OR) indica que as voluntárias com IMC>34 kg/m² e CA>110 cm tiveram 3,7 e 7 vezes, respectivamente, mais chance de apresentarem OA. A obesidade central, seu grau e duração possivelmente contribuem para a incidência da OA de joelhos em mulheres obesas. A circunferência abdominal foi a medida que melhor se correlacionou com a presença e grau de OA em obesas, o que aponta para a relevância de sua mensuração na avaliação clínica.Osteoarthritis (OA) is a degenerative joint disease characterized by inflammatory process, pain, and deformity; one of its main predictive factors is obesity. The aim of this study was to search for possible correlations between anthropometric measures, the Q angle and knee osteoarthritis. A sample of 50 obese women (30 with knee osteoarthritis and 20 with no joint disease), aged between 40 to 60 years, were assessed as to BMI (body mass index), abdominal circumference (AC), waist and hip perimeters (so as to calculate waist-hip ratio), and the Q angle; osteoarthritis was diagnosed by clinical exam and knee joint radiography. Results showed a positive, poor correlation between BMI and Q angle, as well as between time of obesity onset and degree of joint degeneration. AC was found to positively, though weakly, correlate with the degree of joint degeneration and of OA severity. Adjusted odds ratio for OA showed that women with BMI>34 kg/m² and AC>110 cm were respectively 3.7 and 7 times more likely to develop OA. The degree and duration of central obesity possibly contribute to incidence of knee OA in obese women. Abdominal circumference was the measure that most correlated with the degree of joint degeneration and of OA severity, which suggests it should be used in clinical evaluation