Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

Measured and predicted resting energy expenditure in wheelchair rugby athletes

Objective: Report measured resting energy expenditure (REE) in wheelchair rugby athletes and evaluate agreement between REE and the prediction models of Chun, Cunningham, Harris-Benedict, Mifflin, Nightingale and Gorgey, and Owen.

Design: Cohort-based validation study.

Setting. Paralympic team training camp.

Participants: Fourteen internationally competitive athletes who play wheelchair rugby, 13 of whom had cervical spinal cord injuries (SCI).

Outcome Measures: A portable metabolic analyzer was used to measure REE following an overnight fast and dual-energy X-ray absorptiometry (DXA) was used to assess lean body mass for the prediction equations.

Results: REE in the current sample was 1735?±?257?kcal?×?day^?1 ranging from 1324 to 2068?kcal?×?day^{?1 Bhambhani Y. Physiology of wheelchair racing in athletes with spinal cord injury. Sports Med 2002;32(1):23–51.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]}. Bland–Altman analyses revealed negative mean bias but similar limits of agreement between measured REE and scores predicted by Chun, Cunningham, Mifflin, Nightingale and Gorgey, and Owen models in elite athletes who play wheelchair rugby.

Conclusion: Prediction models regressed on persons with and without SCI under-predicted REE of competitive wheelchair rugby athletes. This outcome may be explained by the higher REE/fat-free mass (FFM) ratio of current athletes compared to less active samples. Findings from the current study will help practitioners to determine nutrient intake needs on training days of varied intensity.     

Influence of Fine Grains on the Bending Fatigue Behavior of Two Implant Titanium Alloys

By means of the ultrasonic surface impact (amplitude of 30 μm, strike number of 48,000 times/mm²), nanograins have been achieved in the surfaces of both Ti6Al4V(TC4) and Ti3Zr2Sn3Mo25Nb(TLM) titanium alloys, mainly because of the dislocation motion. Many mechanical properties are improved, such as hardness, residual stress, and roughness. The rotating–bending fatigue limits of TC4 and TLM subjected to ultrasonic impact are improved by 13.1% and 23.7%, separately. Because of the bending fatigue behavior, which is sensitive to the surface condition, cracks usually initiate from the surface defects under high stress amplitude. By means of an ultrasonic impact tip with the size of 8 mm, most of the inner cracks present at the zone with a depth range of 100~250 μm in the high life region. The inner crack core to TC4 usually appears as a deformed long and narrow α-phase, while the cracks in TLM specimens prefer to initiate at the triple grain boundary junctions. This zone crosses the grain refined layer and the deformed coarse grain layer. With the gradient change of elastic parameters, the model shows an increase of normal stress at this zone. Combined with the loss of plasticity and toughness, it is easy to understand these fatigue behaviors.     

Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome

PurposeA role for the immune system in causing myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is long suspected, but few studies have looked for specific autoantibodies that might contribute to the symptoms. Our aim was to look for evidence of antibodies to neuronal proteins in patients with ME/CSF.MethodsSera samples from 50 patients and 50 healthy individuals were sent coded to the Neuroimmunology Laboratory in Oxford. Screening for antibody binding to neuronal tissue was performed on brain tissue and neuronal cultures. Specific serum antibodies were assessed by antigen-specific cell-based assays and radioimmunoassays. After antibody testing, the associations between seropositive status and clinical data were investigated.FindingsOverall, 8 patients and 11 participants were found to have some serum immunoreactivity toward neuronal or neuromuscular junction proteins, but only 1 patient and 2 participants had specific serum antibodies. Nevertheless, seropositive status in patients with ME was associated with shorter duration since onset and a more severe disease.ImplicationsThe results indicate no overall increased frequency of antibodies to neuronal proteins in ME/CSF and no evidence of a specific antibody that might be causative or contribute to clinical features in patients. However, the association of seropositive status with shorter duration of disease and more severe symptoms suggests a possible role of antibodies at onset in some patients and should be the focus of future studies.     

Outcome of isolated posterior cruciate ligament reconstruction at mean 6.3-year follow up: a consecutive case series

Objectives: There is a paucity of reporting on surgical outcomes of isolated posterior cruciate ligament reconstruction (PCLR). We hypothesize that isolated PCL injuries failing nonoperative treatment achieve good outcomes and are able to return to sport following PCLR.

Methods: A retrospective analysis was performed to identify patients with isolated PCL injuries that underwent reconstruction between 2001 and 2014. Patients with multi-ligamentous injury or another concomitant knee pathology were excluded. Medical records were reviewed for demographic, clinical and operative data. Patients were contacted for administration of a telephone-based questionnaire which included the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form, Lysholm-Tegner scales, Marx activity scale (MAS), return to sport status, and patient satisfaction instruments.

Results: A total of 15 isolated PCL reconstructions in 14 patients with a mean age of 27.5 years (range 17–43) met the study inclusion criteria; mean follow up was 6.3 years (range 1.4–15.2). Pre-operatively, the primary complaint was knee instability in all patients; on physical examination, lack of a firm end point during posterior drawer testing was found in 93% (14/15) of the knees. In total, 12 of 15 knees underwent transtibial, single-bundle PCLR and three of 15 underwent tibial inlay, double bundle PCLR. Graft types included: quadriceps autograft (7/15), Achilles allograft (6/15), and hamstring autograft (2/15). There were no graft failures in our patient cohort. At most recent follow up the mean scores respectively on the IKDC form, Lysholm-Tegner scales and MAS were (standard deviation): 77.3 (16.5), 83.1 (17.9), 6.13 (2.6), and 7.1 (6.0). All fourteen patients were athletes prior to their injury and 79% (11/14) returned to sport and overall patient satisfaction was 9.2/10.

Conclusions: Isolated PCLR provides good outcomes at mean medium-term follow up with restoration of function, high rate of return to sport and overall patient satisfaction.