Low-dose SoluMatrix diclofenac in the treatment of osteoarthritis: A 1-year,open-label,Phase III safety study

Introduction. Diclofenac is used for the treatment of osteoarthritis (OA); however, like other nonsteroidal anti-inflammatory drugs (NSAIDs) it can be associated with serious dose-related adverse events (AEs). Low-dose SoluMatrix® diclofenac has been developed to provide efficacy at lower diclofenac doses. A recently published Phase III study evaluated the efficacy and safety of SoluMatrix diclofenac 35 mg twice daily (b.i.d.) and thrice daily (t.i.d.) in patients with OA pain treated for 12 weeks. Methods. This Phase III multicenter, open-label study assessed the safety of SoluMatrix diclofenac in patients with OA dosed up to 52 weeks (ClinicalTrials.gov: NCT01510912). The study enrolled 602 chronic NSAID/acetaminophen users, aged ≥40 years with OA of the knee or hip. Patients received SoluMatrix diclofenac 35 mg b.i.d., which could be increased to t.i.d. and subsequently reduced to b.i.d. as needed. Safety assessments included AEs, vital signs, physical examination findings, 12-lead electrocardiogram, and clinical laboratory test results. Patient-reported outcomes were evaluated by the Short Form-36 (SF-36). Results. A total of 601 patients received SoluMatrix diclofenac; 373 of 601 patients (62.1%) received treatment for ≥11 months. The most frequent AEs included upper respiratory tract infection, headache, urinary tract infection, diarrhea, nasopharyngitis, and nausea. Serious gastrointestinal, cardiovascular, renal, and hepatic AEs were uncommon. A small proportion (99 patients, 16.5%) of patients discontinued participation in the study due to AEs. Clinically meaningful improvements from baseline in Physical Component Summary Scores of the SF-36 were noted at week 12 and were sustained through week 52. Improvements in six of the eight individual physical and mental SF-36 domains were also noted. Conclusion. SoluMatrix diclofenac treatment for up to 1 year was generally well tolerated in patients with OA pain and associated with improvement in quality of life measures. Trial Registration: www.clinicaltrials.gov identifier: NCT01510912.     

Why is the concept of spondyloarthropathies important?

The concept of spondyloarthropathy was recognized first by clinicians based on the aggregation of several diseases occurring either sequentially in the same patient or simultaneously in a family. This concept was thereafter confirmed by the higher prevalence of the HLA-B27 antigen, not only in the group of patients suffering from an axial involvement of ankylosing spondylitis but also in other diseases belonging to the concept of spondyloarthropathy, i.e. psoriatic arthritis, reactive arthritis, inflammatory-bowel-disease-related arthritis and/or other clinical manifestations such as acute anterior uveitis. Recognition of the concept of the spondyloarthropathy is of great importance not only for research purposes but also in daily practice because such recognition has at least a threefold effect: (a) it permits earlier diagnosis, (b) it facilitates patients' education and monitoring, and (c) it has prognostic implications     

Bone health in eating disorders

Eating disorders (EDs) put adolescents and young adults at risk for impaired bone health. Low bone mineral density (BMD) with ED is caused by failure to accrue peak bone mass in adolescence and bone loss in young adulthood. Although ED patients diagnosed with bone loss may be asymptomatic, some suffer bone pains and have increased incidence of fractures. Adolescents with ED are prone to increased prevalence of stress fractures, kyphoscoliosis and height loss. The clinical picture of the various EDs involves endocrinopathies that contribute to impaired bone health. Anorexia nervosa (AN) is characterized by low bone turnover, with relatively higher osteoclastic (bone resorptive) than osteoblastic (bone formation) activity. Bone loss in AN occurs in both the trabecular and cortical bones, although the former is more vulnerable. Bone loss in AN has been shown to be influenced by malnutrition and low weight, reduced fat mass, oestrogen and androgen deficiency, glucocorticoid excess, impaired growth hormone–insulin‐like growth factor 1 axis, and more. Bone loss in AN may not be completely reversible despite recovery from the illness. Treatment modalities involving hormonal therapies have limited effectiveness, whereas increased caloric intake, weight gain and resumption of menses are essential to improved BMD.     

Unexpected Recovery of Function After Severe Traumatic Brain Injury: The Limits of Early Neuroimaging-Based Outcome Prediction

Background

Prognostication in the early stage of traumatic coma is a common challenge in the neuro-intensive care unit. We report the unexpected recovery of functional milestones (i.e., consciousness, communication, and community reintegration) in a 19-year-old man who sustained a severe traumatic brain injury. The early magnetic resonance imaging (MRI) findings, at the time, suggested a poor prognosis.

Methods

During the first year of the patient’s recovery, MRI with diffusion tensor imaging and T2*-weighted imaging was performed on day 8 (coma), day 44 (minimally conscious state), day 198 (post-traumatic confusional state), and day 366 (community reintegration). Mean apparent diffusion coefficient (ADC) and fractional anisotropy values in the corpus callosum, cerebral hemispheric white matter, and thalamus were compared with clinical assessments using the Disability Rating Scale (DRS).

Results

Extensive diffusion restriction in the corpus callosum and bihemispheric white matter was observed on day 8, with ADC values in a range typically associated with neurotoxic injury (230–400 × 10^?6 mm²/s). T2*-weighted MRI revealed widespread hemorrhagic axonal injury in the cerebral hemispheres, corpus callosum, and brainstem. Despite the presence of severe axonal injury on early MRI, the patient regained the ability to communicate and perform activities of daily living independently at 1 year post-injury (DRS = 8).

Conclusions

MRI data should be interpreted with caution when prognosticating for patients in traumatic coma. Recovery of consciousness and community reintegration are possible even when extensive traumatic axonal injury is demonstrated by early MRI.     

WHO-5, a tool focusing on psychological needs in patients with diabetes: The French contribution to the DAWN study

AimIn 2001, the international Diabetes Attitudes, Wishes and Needs (DAWN) programme was launched to evaluate the psychosocial impact of diabetes. In France, DAWN experts carried out an observational study to further understand the impact of diabetes on the psychological well-being of people with diabetes, using the French version of the WHO-5 questionnaire.MethodsThe WHO-5, a unidimensional five-item questionnaire that measures positive psychological well-being, was completed by 2213 patients (1670 with diabetes). A total sum score was calculated, ranging on a scale from 0 to 25. A score less than 13 indicated impaired well-being and a score less than 8 reflected likely depression.ResultsThe mean total well-being score for the whole study population was 14.1 ± 5.5, and 14.3 ± 5.5 for patients with diabetes and 13.5 ± 5.4 for patients with other chronic diseases. The average score for patients with diabetes only (15.1 ± 5.2) was higher than those for the other subgroups (P = 0.005), whereas the average scores for those using insulin (14.8 ± 5.2) and women with diabetes (13.2 ± 5.6) were significantly lower compared with the whole diabetic group (15.6 ± 5.1 [P = 0.03] and 15 ± 5.2 [P < 0.001], respectively).ConclusionThe WHO-5 questionnaire showed satisfactory psychometric properties in a large sample of French diabetic patients. The scale is unidimensional and highlighted differences in well-being, which was lower in diabetic women, in patients with other chronic diseases and in those treated with insulin.     

Hypothalamic obesity in children

Hypothalamic obesity is an intractable form of obesity syndrome that was initially described in patients with hypothalamic tumours and surgical damage. However, this definition is now expanded to include obesity developing after a variety of insults, including intracranial infections, infiltrations, trauma, vascular problems and hydrocephalus, in addition to acquired or congenital functional defects in central energy homeostasis in children with the so‐called common obesity. The pathogenetic mechanisms underlying hypothalamic obesity are complex and multifactorial. Weight gain results from damage to the ventromedial hypothalamus, which leads, variously, to hyperphagia, a low‐resting metabolic rate; autonomic imbalance; growth hormone‐, gonadotropins and thyroid‐stimulating hormone deficiency; hypomobility; and insomnia. Hypothalamic obesity did not receive enough attention, as evidenced by rarity of studies in this group of patients. A satellite symposium was held during the European Congress of Obesity in May 2011, in Istanbul, Turkey, to discuss recent developments and concepts regarding pathophysiology and management of hypothalamic obesity in children. An international group of leading researchers presented certain aspects of the problem. This paper summarizes the highlights of this symposium. Understanding the central role of the hypothalamus in the regulation of feeding and energy metabolism will help us gain insights into the pathogenesis and management of common obesity.     

Vaccine administration decision making: the case of yellow Fever vaccine

Background.?Providers must counsel travelers to yellow fever (YF)-endemic areas, although risk estimates of disease and vaccine serious adverse events (SAEs) may be imprecise. The impact of risk information and patients' requests for participation in vaccine decisions on providers' recommendations is unknown. Methods.?Vaccine providers were surveyed regarding decisions for 4 patient scenarios before and after being presented information about risk of YF disease vs vaccine SAEs. Participants' theoretical attitudes were compared with actual responses to scenarios in which patients wanted to share vaccine decisions. Analyses were done by using χ(2) tests with significance level of .05. Results.?Forty-six percent of respondents made appropriate initial YF vaccine administration decisions for a pregnant woman, 73% for an immunosuppressed man, and 49% for an 8-month-old infant. After receiving scenario-specific information, 20%, 54%, and 23% of respondents respectively who initially responded incorrectly changed to a more appropriate decision. Thirty-one percent of participants made consistently appropriate decisions. Among participants who made ≥1 incorrect decision, 35.7% made no decision changes after receiving information. In the scenario in which either a decision to withhold or to administer vaccine was acceptable, 19% of respondents refused a patient's request for vaccine. Conclusions.?Targeted information is necessary but insufficient to change the process of vaccine administration decision making. Providers need additional education to enable them to apply evidence, overcome cognitive decision-making errors, and involve patients in vaccine decisions.     

Osteoporosis and Osteoarthritis, Rheumatoid Arthritis and Spondylarthropathies

Osteoporosis (OP) commonly occurs in the setting of inflammatory arthritis, whereas there is an inverse relationship with osteoarthritis (OA). We review the recent updates in epidemiology and pathophysiology of OP relating to several arthridities. In ankylosing spondylitis, lateral lumbar spine dual x-ray absorptiometry is better at detecting osteoporosis compared with the AP view and patients receiving treatment with anti- tumor necrosis factor medications had lower levels of bone turnover markers. With regard to rheumatoid arthritis, anticitrullinated peptide positivity without clinical arthritis as well as higher levels of interleukin-6 is associated with decreased bone mineral density and polymorphisms in the vitamin D receptor in RA patients may predispose to OP. With regard to OA, results from the Global Longitudinal Study of Osteoporosis in Women study and several radiological studies suggest that differences in the distribution of bone mass at the femoral neck may account for the inverse relationship of OA and OP, and several studies suggest that OA and OP have opposing cytokine and bone metabolism marker profiles.