When rheumatology meets hepatology: are anti-TNFs safe in hepatitis B virus carriers?

Over the past decades, more effective and less toxic biologicals have revolutionized rheumatology therapy in our battle against the autoimmune chronic inflammation of rheumatoid arthritis and spondyloarthropathy. But what about for patients who have previously had an infection of the liver? Prior hepatitis B virus infection clearly presents a challenge for clinicians. In a study by Charpin and colleagues of 21 patients whose hepatitis B virus serology suggested carrier status, anti-TNF treatment appeared to be safe during a limited follow-up period of 3 years. Studies are needed with longer follow-up, particularly in patients with low antibody titres (antiHBc). In the 3-year period, however, about 30% of the patients developed significant lowering of antibody titres, which may become relevant during long-term follow-up. Charpin and colleagues are the first to reveal promising data on the relative safety of anti-TNFs in a small series of hepatitis B carriers for up to 3 years

Quantum Continuum Mechanics Made Simple

In this paper we further explore and develop the quantum continuum mechanics (CM) of [Tao \emph{et al}, PRL{\bf 103},086401] with the aim of making it simpler to use in practice. Our simplifications relate to the non-interacting part of the CM equations, and primarily refer to practical implementations in which the groundstate stress tensor is approximated by its Kohn-Sham version. We use the simplified approach to directly prove the exactness of CM for one-electron systems via an orthonormal formulation. This proof sheds light on certain physical considerations contained in the CM theory and their implication on CM-based approximations. The one-electron proof then motivates an approximation to the CM (exact under certain conditions) expanded on the wavefunctions of the Kohn-Sham (KS) equations. Particular attention is paid to the relationships between transitions from occupied to unoccupied KS orbitals and their approximations under the CM. We also demonstrate the simplified CM semi-analytically on an example system

Bringing focus to entrepreneurship

Fostering entrepreneurship has long been a core part of the RSM ethos. But a new centre bringing together some key players promises to take this philosophy to a new and even more successful level

Inability to obtain deferred consent due to early death in emergency research: effect on validity of clinical trial results

PURPOSE: To illustrate the impact on the validity of trial results due to excluding patients from a randomized controlled trial for whom no deferred consent could be obtained after randomization because study procedures had already been finished. METHODS: The unadjusted and adjusted primary outcome measures of a recent randomized controlled multicentre study in the field of intensive care medicine were compared, including (n = 348) or excluding (n = 289) patients with missing deferred consent. RESULTS: Thirty-nine patients (11%) died early, before the patient or his/her proxy could be approached and consent be obtained. In another 20 patients (6%), it was not possible to inform proxies and ask consent within the period of study procedures. A significant treatment effect (p = 0.006) in the adjusted analysis became non-significant (p = 0.35) when the patients with missing deferred consent were excluded. CONCLUSIONS: Exclusion of patients without obtained deferred consent can reduce statistical power, introduce selection bias, make randomization asymmetrical, decrease external validity and thereby jeopardize study results. This may have implications for emergency research in various disciplines

Management of hyperuricemia in gout: focus on febuxostat

Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than “standard dosage” allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol

Clinical use of lactate monitoring in critically ill patients

Increased blood lactate levels (hyperlactataemia) are common in critically ill patients. Although frequently used to diagnose inadequate tissue oxygenation, other processes not related to tissue oxygenation may increase lactate levels. Especially in critically ill patients, increased glycolysis may be an important cause of hyperlactataemia. Nevertheless, the presence of increased lactate levels has important implications for the morbidity and mortality of the hyperlactataemic patients. Although the term lactic acidosis is frequently used, a significant relationship between lactate and pH only exists at higher lactate levels. The term lactate associated acidosis is therefore more appropriate. Two recent studies have underscored the importance of monitoring lactate levels and adjust treatment to the change in lactate levels in early resuscitation. As lactate levels can be measured rapidly at the bedside from various sources, structured lactate measurements should be incorporated in resuscitation protocols