Elderly-onset rheumatoid arthritis

The treatment of elderly-onset rheumatoid arthritis pursues the same objectives as in younger patients: to control the clinical manifestations, to prevent structural damage, to preserve function, and to decrease excess mortality. In the elderly, the presence of co-morbidities and increased rate of drug-related adverse effects raise specific therapeutic challenges. Nonsteroidal anti-inflammatory drugs are associated with cardiovascular, gastrointestinal, and renal adverse events. The role for corticosteroid therapy remains controversial. Although glucocorticoids provide a short-term decrease in clinical activity and probably a medium-term decrease in structural damage, these benefits are offset by numerous adverse effects. Methotrexate was effective in clinical trials and observational studies and did not produce a higher adverse event rate compared to younger patients, provided renal function was normal. Data on the efficacy of TNFα antagonists in therapeutic trials are available only for etanercept. Disease activity decreased and function improved. The adverse event rate was higher in older patients, but this was also true of the conventional drugs used as comparators. Registry data confirm that TNFα antagonist therapy is effective in RA. An increased rate of infections was found only in some registries. To combat the 2-fold cardiovascular risk increase associated with RA, disease activity should be stringently controlled and all cardiovascular risk factors managed aggressively.     

Analysis of core circadian feedback loop in suprachiasmatic nucleus of mCry1-luc transgenic reporter mouse

The suprachiasmatic nucleus (SCN) coordinates circadian rhythms that adapt the individual to solar time. SCN pacemaking revolves around feedback loops in which expression of Period (Per) and Cryptochrome (Cry) genes is periodically suppressed by their protein products. Specifically, PER/CRY complexes act at E-box sequences in Per and Cry to inhibit their transactivation by CLOCK/BMAL1 heterodimers. To function effectively, these closed intracellular loops need to be synchronized between SCN cells and to the light/dark cycle. For Per expression, this is mediated by neuropeptidergic and glutamatergic extracellular cues acting via cAMP/calcium-responsive elements (CREs) in Per genes. Cry genes, however, carry no CREs, and how CRY-dependent SCN pacemaking is synchronized remains unclear. Furthermore, whereas reporter lines are available to explore Per circadian expression in real time, no Cry equivalent exists. We therefore created a mouse, B6.Cg-Tg(Cry1-luc)01Ld, carrying a transgene (mCry1-luc) consisting of mCry1 elements containing an E-box and E′-box driving firefly luciferase. mCry1-luc organotypic SCN slices exhibited stable circadian bioluminescence rhythms with appropriate phase, period, profile, and spatial organization. In SCN lacking vasoactive intestinal peptide or its receptor, mCry1 expression was damped and desynchronized between cells. Despite the absence of CREs, mCry1-luc expression was nevertheless (indirectly) sensitive to manipulation of cAMP-dependent signaling. In mPer1/2-null SCN, mCry1-luc bioluminescence was arrhythmic and no longer suppressed by elevation of cAMP. Finally, an SCN graft procedure showed that PER-independent as well as PER-dependent mechanisms could sustain circadian expression of mCry1. The mCry1-luc mouse therefore reports circadian mCry1 expression and its interactions with vasoactive intestinal peptide, cAMP, and PER at the heart of the SCN pacemaker.     

Prevalence of Thoracic Aortic Aneurysms in Patients with Degenerative Abdominal Aortic Aneurysms: Results from the Prospective ACTA Study

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Retrospective analysis of physical therapy utilization by the specificity of the diagnosis and order written on the referral

Background: Arguments against reimbursement for direct access to physical therapy (PT) are that a physician examination is necessary to diagnose and that there is a potential for increased cost. Objective: To determine what percentage of PT referrals had a specific diagnosis and treatment orders. Additionally, specific and non-specific diagnoses and treatment orders were compared in regards to PT units billed, average visits per referral, and average cost per referral. Methods: The charts of 1,000 patients treated in outpatient PT underwent a retrospective chart review. Interferential statistics were used to determine if there was a statistically significant difference between specific and non-specific diagnoses and treatment orders in regard to PT units billed, average visits per referral, and average cost per referral. Results: Twenty-nine percent of all referring diagnoses were non-specific in nature and 58% contained treatment orders that were non-specific. Charts with a specific diagnosis had a statistically significant higher utilization as compared to non-specific diagnoses (p ≤ 0.001). Patients with a specific treatment order also displayed a statistically significant larger average in billed units, average visits per referral, and average reimbursement per referral than those without a specific treatment order (p ≤ 0.0001). Conclusion: Our findings suggest that a physician diagnosis and referral may not be required to direct care for patients seeking PT services. Third-party payers that require a physician referral for PT services may be delaying access to healthcare and increasing costs.     

Shigella spp. with Reduced Azithromycin Susceptibility,Quebec, Canada, 2012–2013

During 2012–2013 in Montreal, Canada, 4 locally acquired Shigella spp. pulse types with the mph(A) gene and reduced susceptibility to azithromycin were identified from 9 men who have sex with men, 7 of whom were HIV infected. Counseling about prevention of enteric sexually transmitted infections might help slow transmission of these organisms.