Analysing trajectories of a longitudinal exposure: A causal perspective on common methods in lifecourse research

Longitudinal data is commonly analysed to inform prevention policies for diseases that may develop throughout life. Commonly methods interpret the longitudinal data as a series of discrete measurements or as continuous patterns. Some of the latter methods condition on the outcome, aiming to capture ‘average’ patterns within outcome groups, while others capture individual-level pattern features before relating these to the outcome. Conditioning on the outcome may prevent meaningful interpretation. Repeated measurements of a longitudinal exposure (weight) and later outcome (glycated haemoglobin levels) were simulated to match three scenarios: one with no causal relationship between growth rate and glycated haemoglobin; two with a positive causal effect of growth rate on glycated haemoglobin. Two methods that condition on the outcome and one that did not were applied to the data in 1000 simulations. The interpretation of the two-step method matched the simulation in all causal scenarios, but that of the methods conditioning on the outcome did not. Methods that condition on the outcome do not accurately represent a causal relationship between a longitudinal pattern and outcome. Researchers considering longitudinal data should carefully determine if they wish to analyse longitudinal data as a series of discrete time points or by extracting pattern features

Initial intramuscular perfusion pressure predicts early skeletal muscle function following isolated tibial fractures

<p>Abstract</p> <p>Background</p> <p>The severity of associated soft tissue trauma in complex injuries of the extremities guides fracture treatment and decisively determines patient's prognosis. Trauma-induced microvascular dysfunction and increased tissue pressure is known to trigger secondary soft tissue damage and seems to adversely affect skeletal muscle function.</p> <p>Methods</p> <p>20 patients with isolated tibial fractures were included. Blood pressure and compartment pressure (anterior and deep posterior compartment) were measured continuously up to 24 hours. Corresponding perfusion pressure was calculated. After 4 and 12 weeks isokinetic muscle peak torque and mean power of the ankle joint in dorsal and plantar flexion were measured using a Biodex dynamometer.</p> <p>Results</p> <p>A significant inverse correlation between the anterior perfusion pressure at 24 hours and deficit in dorsiflexion at 4 weeks was found for both, the peak torque (R = -0.83; p < 0.01) and the mean power (R = -0.84; p < 0.01). The posterior perfusion pressure at 24 h and the plantar flexion after 4 weeks in both, peak torque (R = -0.73, p =< 0.05) and mean power (R = -0.7, p =< 0.05) displayed a significant correlation.</p> <p>Conclusion</p> <p>The functional relationship between the decrease in intramuscular perfusion pressures and muscle performance in the early rehabilitation period indicate a causative and prognostic role of early posttraumatic microcirculatory derangements and skeletal muscle function. Therapeutic concepts aimed at effective muscle recovery, early rehabilitation, and decreased secondary tissue damage, should consider the maintenance of an adequate intramuscular perfusion pressure.</p

Ca(2+) signaling by T-type Ca(2+) channels in neurons.

Among the major families of voltage-gated Ca(2+) channels, the low-voltage-activated channels formed by the Ca(v)3 subunits, referred to as T-type Ca(2+) channels, have recently gained increased interest in terms of the intracellular Ca(2+) signals generated upon their activation. Here, we provide an overview of recent reports documenting that T-type Ca(2+) channels act as an important Ca(2+) source in a wide range of neuronal cell types. The work is focused on T-type Ca(2+) channels in neurons, but refers to non-neuronal cells in cases where exemplary functions for Ca(2+) entering through T-type Ca(2+) channels have been described. Notably, Ca(2+) influx through T-type Ca(2+) channels is the predominant Ca(2+) source in several neuronal cell types and carries out specific signaling roles. We also emphasize that Ca(2+) signaling through T-type Ca(2+) channels occurs often in select subcellular compartments, is mediated through strategically co-localized targets, and is exploited for unique physiological functions

Body mass index and complications following major gastrointestinal surgery: a prospective, international cohort study and meta-analysis.

AIM: Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a meta-analysis of all available prospective data. METHODS: This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien-Dindo Grades III-V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. RESULTS: This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery for malignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49-2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46-0.75, P < 0.001) compared to normal weight patients. CONCLUSIONS: In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease