Deflazacort for the treatment of Duchenne Dystrophy: A systematic review

BACKGROUND: To complete a systematic review and meta-analysis based on the clinical question: Is Deflazacort (DFZ), a prednisolone derivative, an effective therapy for improving strength, with acceptable side effects, in children with Duchenne Dystrophy (DD)? METHODS: MEDLINE, EMBASE, Current Contents, Dissertation Abstracts, Health Star, PsychINFO and Cochrane, were searched using the following inclusion criteria: 1) A randomized controlled trial comparing DFZ with placebo or another therapy; 2) Male participants age 2–18 years with DD; 3) Outcomes of (a) any form of strength or functional testing, or (b) any form of side effect. RESULTS: Fifteen studies of potential relevance were identified, with five meeting the inclusion criteria. These five studies included 291 children and were published in English language journals between 1994 and 2000. Two studies compared DFZ versus placebo, two studies compared DFZ with prednisone and one study had both placebo and prednisone comparisions. Two large trials were identified that have not been published in article format. Due to the heterogeneity in outcome measures and the inconsistent reporting of summary statistics a meta-analytic approach could not be taken. CONCLUSIONS: Examining individual studies it appears that DFZ improves strength and functional outcomes compared to placebo, but it remains unclear if it has a benefit over prednisone on similar outcomes. Two trials found that DFZ causes less weight gain than prednisone

The spatial extent of tephra deposition and environmental impacts from the 1912 Novarupta eruption

The eruption of Novarupta within the Katmai Volcanic Cluster, south-west Alaska, in June 1912 was the most voluminous eruption of the twentieth century but the distal distribution of tephra deposition is inadequately quantified. We present new syntheses of published tephrostratigraphic studies and a large quantity of previously un-investigated historical records. For the first time, we apply a geostatistical technique, indicator kriging, to integrate and interpolate such data. Our results show evidence for tephra deposition across much of Alaska, Yukon, the northern Pacific, western British Columbia and northwestern Washington. The most distal tephra deposition was observed around 2,500 km downwind from the volcano. Associated with tephra deposition are many accounts of acid deposition and consequent impacts on vegetation and human health. Kriging offers several advantages as a means to integrate and present such data. Future eruptions of a scale similar to the 1912 event have the potential to cause widespread disruption. Historical records of tephra deposition extend far beyond the limit of deposition constrained by tephrostratigraphic records. The distal portion of tephra fallout deposits is rarely adequately mapped by tephrostratigraphy alone; contemporaneous reports of fallout can provide important constraints on the extent of impacts following large explosive eruptions

Access and utilisation of primary health care services comparing urban and rural areas of Riyadh Providence, Kingdom of Saudi Arabia

The Kingdom of Saudi Arabia (KSA) has seen an increase in chronic diseases. International evidence suggests that early intervention is the best approach to reduce the burden of chronic disease. However, the limited research available suggests that health care access remains unequal, with rural populations having the poorest access to and utilisation of primary health care centres and, consequently, the poorest health outcomes. This study aimed to examine the factors influencing the access to and utilisation of primary health care centres in urban and rural areas of Riyadh province of the KSA

Adhesive capsulitis and dynamic splinting: a controlled, cohort study

<p>Abstract</p> <p>Background</p> <p>Adhesive Capsulitis (AC) affects patient of all ages, and stretching protocols are commonly prescribed for this condition. Dynamic splinting has been shown effective in contracture reduction from pathologies including Trismus to plantar fasciitis. The purpose of this study was to examine the efficacy of dynamic splinting on patients with AC.</p> <p>Methods</p> <p>This controlled, cohort study, was conducted at four physical therapy, sports medicine clinics in Texas and California. Sixty-two patients diagnosed with Stage II Adhesive Capsulitis were grouped by intervention. The intervention categories were as follows: Group I (Control); Group II (Physical Therapy exclusively with standardized protocols); Group III; (Shoulder Dynasplint system exclusively); Group IV (Combined treatment with Shoulder Dynasplint and standardized Physical Therapy). The duration of this study was 90 days for all groups, and the main outcome measures were change in active, external rotation.</p> <p>Results</p> <p>Significant difference was found for all treatment groups (p < 0.001) following a one-way ANOVA. The greatest change with the smallest standard deviation was for the combined treatment group IV, (mean change of 29°).</p> <p>Conclusion</p> <p>The difference for the combined treatment group was attributed to patients' receiving the best PT combined with structured "home therapy" that contributed an additional 90 hours of end-range stretching. This adjunct should be included in the standard of care for adhesive Capsulitis.</p> <p>Trial Registration</p> <p><b>Trial Number</b>: NCT00873158</p

The Prevalence and Cost of Unapproved Uses of Top-Selling Orphan Drugs

Introduction: The Orphan Drug Act encourages drug development for rare conditions. However, some orphan drugs become top sellers for unclear reasons. We sought to evaluate the extent and cost of approved and unapproved uses of orphan drugs with the highest unit sales. Methods We assessed prescription patterns for four top-selling orphan drugs: lidocaine patch (Lidoderm) approved for post-herpetic neuralgia, modafinil (Provigil) approved for narcolepsy, cinacalcet (Sensipar) approved for hypercalcemia of parathyroid carcinoma, and imatinib (Gleevec) approved for chronic myelogenous leukemia and gastrointestinal stromal tumor. We pooled patient-specific diagnosis and prescription data from two large US state pharmaceutical benefit programs for the elderly. We analyzed the number of new and total patients using each drug and patterns of reimbursement for approved and unapproved uses. For lidocaine patch, we subcategorized approved prescriptions into two subtypes of unapproved uses: neuropathic pain, for which some evidence of efficacy exists, and non-neuropathic pain. Results: We found that prescriptions for lidocaine patch, modafinil, and cinacalcet associated with non-orphan diagnoses rose at substantially higher rates (average monthly increases in number of patients of 14.6, 1.45, and 1.58) than prescriptions associated with their orphan diagnoses (3.12, 0.24, and 0.03, respectively (p75%). Increases in lidocaine patch use for non-neuropathic pain far exceeded neuropathic pain (10.2 vs. 3.6 patients, p<0.001). Discussion In our sample, three of four top-selling orphan drugs were used more commonly for non-orphan indications. These orphan drugs treated common clinical symptoms (pain and fatigue) or laboratory abnormalities. We should continue to monitor orphan drug use after approval to identify products that come to be widely used for non-FDA approved indications, particularly those without adequate evidence of efficacy

Barriers to adequate follow-up during adjuvant therapy may be important factors in the worse outcome for Black women after breast cancer treatment

<p>Abstract</p> <p>Introduction</p> <p>Black women appear to have worse outcome after diagnosis and treatment of breast cancer. It is still unclear if this is because Black race is more often associated with known negative prognostic indicators or if it is an independent prognostic factor. To study this, we analyzed a patient cohort from an urban university medical center where these women made up the majority of the patient population.</p> <p>Methods</p> <p>We used retrospective analysis of a prospectively collected database of breast cancer patients seen from May 1999 to June 2006. Time to recurrence and survival were analyzed using the Kaplan-Meier method, with statistical analysis by chi-square, log rank testing, and the Cox regression model.</p> <p>Results</p> <p>265 female patients were diagnosed with breast cancer during the time period. Fifty patients (19%) had pure DCIS and 215 patients (81%) had invasive disease. Racial and ethnic composition of the entire cohort was as follows: Black (N = 150, 56.6%), Hispanic (N = 83, 31.3%), Caucasian (N = 26, 9.8%), Asian (N = 4, 1.5%), and Arabic (N = 2, 0.8%). For patients with invasive disease, independent predictors of poor disease-free survival included tumor size, node-positivity, incompletion of adjuvant therapy, and Black race. Tumor size, node-positivity, and Black race were independently associated with disease-specific overall survival.</p> <p>Conclusion</p> <p>Worse outcome among Black women appears to be independent of the usual predictors of survival. Further investigation is necessary to identify the cause of this survival disparity. Barriers to completion of standard post-operative treatment regimens may be especially important in this regard.</p

Trigger finger: etiology, evaluation, and treatment

Trigger finger is a common finger aliment, thought to be caused by inflammation and subsequent narrowing of the A1 pulley, which causes pain, clicking, catching, and loss of motion of the affected finger. Although it can occur in anyone, it is seen more frequently in the diabetic population and in women, typically in the fifth to sixth decade of life. The diagnosis is usually fairly straightforward, as most patients complain of clicking or locking of the finger, but other pathological processes such as fracture, tumor, or other traumatic soft tissue injuries must be excluded. Treatment modalities, including splinting, corticosteroid injection, or surgical release, are very effective and are tailored to the severity and duration of symptoms

Volcanic impacts on the Holocene vegetation history of Britain and Ireland? A review and meta-analysis of the pollen evidence

Volcanic ash layers show that the products of Icelandic volcanism reached Britain and Ireland many times during the Holocene. Historical records suggest that at least one eruption, that of Laki in a.d. 1783, was associated with impacts on vegetation. These results raise the question: did Icelandic volcanism affect the Holocene vegetation history of Britain and Ireland? Several studies have used pollen data to address this issue but no clear consensus has been reached. We re-analyse the palynological data using constrained ordination with various representations of potential volcanic impacts. We find that the palynological evidence for volcanic impacts on vegetation is weak but suggest that this is a case of absence of evidence and is not necessarily evidence of absence of impact. To increase the chances of identifying volcanic impacts, future studies need to maximise temporal resolution, replicate results, and investigate a greater number of tephras in a broader range of locations, including more studies from lake sediments

Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics

© 2018 The Author(s). Atopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDM S ) subjects with/without wheezing history that are characteristic of the ongoing asthmatic state. The expression of type 2 effectors (IL-5, IL-13) was equivalent in both cohorts of subjects. However, in HDM S -wheezers they were associated with upregulation of two coexpression modules comprising multiple type 2- and epithelial-associated genes. The first module was interlinked by the hubs EGFR, ERBB2, CDH1 and IL-13. The second module was associated with CDHR3 and mucociliary clearance genes. Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatics undergoing natural aeroallergen exposure, and suggest that susceptibility to asthma amongst these subjects involves complex interactions between type 2- and epithelial-associated gene networks, which are not operative in equivalently sensitized/exposed atopic non-asthmatics