In patients eligible for meniscal surgery who first receive physical therapy, multivariable prognostic models cannot predict who will eventually undergo surgery

Purpose Although physical therapy is the recommended treatment in patients over 45 years old with a degenerative meniscal tear, 24% still opt for meniscal surgery. The aim was to identify those patients with a degenerative meniscal tear who will undergo surgery following physical therapy. Methods The data for this study were generated in the physical therapy arm of the ESCAPE trial, a randomized clinical trial investigating the effectiveness of surgery versus physical therapy in patients of 45-70 years old, with a degenerative meniscal tear. At 6 and 24 months patients were divided into two groups: those who did not undergo surgery, and those who did undergo surgery. Two multivariable prognostic models were developed using candidate predictors that were selected from the list of the patients' baseline variables. A multivariable logistic regression analysis was performed with backward Wald selection and a cut-off of p < 0.157. For both models the performance was assessed and corrected for the models' optimism through an internal validation using bootstrapping technique with 500 repetitions. Results At 6 months, 32/153 patients (20.9%) underwent meniscal surgery following physical therapy. Based on the multivariable regression analysis, patients were more likely to opt for meniscal surgery within 6 months when they had worse knee function, lower education level and a better general physical health status at baseline. At 24 months, 43/153 patients (28.1%) underwent meniscal surgery following physical therapy. Patients were more likely to opt for meniscal surgery within 24 months when they had worse knee function and a lower level of education at baseline at baseline. Both models had a low explained variance (16 and 11%, respectively) and an insufficient predictive accuracy. Conclusion Not all patients with degenerative meniscal tears experience beneficial results following physical therapy. The non-responders to physical therapy could not accurately be predicted by our prognostic models.Orthopaedics, Trauma Surgery and Rehabilitatio

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease : An open-label multicentre randomised controlled trial

Objective: In newly diagnosed paediatric patients with moderate-to-severe Crohn's disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment. Design: In this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3-17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI <12.5 at week 52, without need for treatment escalation, using intention-to-treat analysis. Results: 100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was not significantly different (p=0.421). However, 19/46 (41%) patients in the FL-IFX group were in clinical remission on azathioprine monotherapy without need for treatment escalation vs 7/48 (15%) in the conventional group (p=0.004). Conclusions: FL-IFX was superior to conventional treatment in achieving short-term clinical and endoscopic remission, and had greater likelihood of maintaining clinical remission at week 52 on azathioprine monotherapy. Trial registration number: ClinicalTrials.gov Registry (NCT02517684).publishedVersionPeer reviewe