Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

Fast track rehabilitation after reversed total shoulder arthroplasty: a protocol for an international multicentre prospective cohort study.

INTRODUCTION: The use of reversed total shoulder arthroplasty (rTSA) has increased because of an increasing number of indications for this procedure and by ageing of the population. Usual postoperative care consists of immobilisation of the shoulder for a period of 2-6 weeks to allow healing of the subscapularis tendon and protection of the joint. However, new literature proved that reattachment of the subscapularis tendon is unnecessary. Therefore we hypothesised that immobilisation of the shoulder is not necessary and patients can start safely with mobilisation on the first postoperative day. We expect this fast track protocol to be safe and result in better short-term and long-term functional outcomes. METHODS AND ANALYSIS: In our prospective cohort, we will include at least 75 patients aged 50 years and older indicated for rTSA, with acute fracture treatment as an exclusion criterion. Patients will be selected and operated in three hospitals: two in the Netherlands and one in Curacao.Patients will visit the outpatient clinic preoperative, at 6 weeks, 3 months and 1 year postoperative. The data that will be collected includes baseline characteristics, reason for surgery, complications and adverse events, patient reported outcomes (Oxford Shoulder Score, EuroQol-5D and Numeric Rating Scale for pain) and range of motion of the shoulder.All patients will be instructed to use a sling only for 1 day and to follow a progressive physiotherapy schedule for 12 weeks. The primary outcome is the occurrence of complications and adverse events. ETHICS AND DISSEMINATION: The Medical Ethics Committee from the VUmc and Curacao reviewed this study protocol and granted exemption from ethical approval (METC VUmc 2019.111, METC Curacao 2019-02). Study results will be presented at (inter)national conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL7656).

The SSQ model of schizophrenic prodromal unfolding revised: an analysis of its causal chains based on the language of directed graphs.

OBJECTIVE: Except in broad outline, little is known about the most likely symptomatic trajectories in prodromal schizophrenia. The aim of this study is to delineate these pathways. METHODS: Taking into account existing clinical knowledge, the causal relationships between the 12 prodrome scales of the Schizotypic Syndrome Questionnaire (SSQ) were examined in a general-population sample by applying the mathematical theory of directed graphs. Use was made of two discovery algorithms implemented in the Tetrad-4 program, as well as of the graphical DAGitty program to test whether a particular model holds. RESULTS: A promising model was selected that may describe the causal pathways in schizophrenic prodromal unfolding. Testing this model by means of DAGitty, it was shown that the minimal testable implications, listed as conditional independences, and the direct and total effects in the model, identified after correction for bias, were as hypothesized. For practical reasons, a simpler version of the resulting SSQ model, containing only its principal pathways, was provided. CONCLUSIONS: Although resembling an earlier model that was based on a series of LISREL analyses, the present model was believed to provide a more dependable description of schizophrenic prodromal unfolding, as it relies on methods that are less subject to the limitations involved in SEM.