The Importance of Time Congruity in the Organisation.

In 1991 Kaufman, Lane, and Lindquist proposed that time congruity in terms of an individual's time preferences and the time use methods of an organisation would lead to satisfactory performance and enhancement of quality of work and general life. The research reported here presents a study which uses commensurate person and job measures of time personality in an organisational setting to assess the effects of time congruity on one aspect of work life, job-related affective well-being. Results show that time personality and time congruity were found to have direct effects on well-being and the influence of time congruity was found to be mediated through time personality, thus contributing to the person–job (P–J) fit literature which suggests that direct effects are often more important than indirect effects. The study also provides some practical examples of ways to address some of the previously cited methodological issues in P–J fit research

The epidemiology of osteonecrosis: findings from the GPRD and THIN databases in the UK

Summary We conducted a case–control study to examine osteonecrosis (ON) incidence, patient characteristics, and selected potential risk factors using two health record databases in the UK. Statistically significant risk factors for ON included systemic corticosteroid use, hospitalization, referral or specialist visit, bone fracture, any cancer, osteoporosis, connective tissue disease, and osteoarthritis.Introduction The purpose of this case–control study was to examine the incidence of osteonecrosis (ON), patient characteristics, and selected potential risk factors for ON using two health record databases in the UK: the General Practice Research Database and The Health Improvement Network.Methods ON cases (n? =?792) were identified from 1989 to 2003 and individually matched (age, sex, and medical practice) up to six controls (n?=?4,660) with no record of ON. Possible risk factors were considered for inclusion based on a review of published literature. Annual incidence rates were computed, and a multivariable logistic regression model was derived to evaluate selected risk factors.Results ON of the hip represented the majority of cases (75.9%). Statistically significant risk factors for ON were systemic corticosteroid use in the previous 2 years, hospitalization, referral or specialist visit, bone fracture, any cancer, osteoporosis, connective tissue disease, and osteoarthritis within the past 5 years. Only 4.4% of ON cases were exposed to bisphosphonates within the previous 2 years.Conclusions This study provides further perspective on the descriptive epidemiology of ON. Studies utilizing more recent data may further elucidate the understanding of ON key predictors.<br/

Preoperative Exercise Training to Prevent Postoperative Pulmonary Complications in Adults Undergoing Major Surgery. A Systematic Review and Meta-analysis with Trial Sequential Analysis.

Rationale: Poor preoperative physical fitness and respiratory muscle weakness are associated with postoperative pulmonary complications (PPCs) that result in prolonged hospital length of stay and increased mortality.Objectives: To examine the effect of preoperative exercise training on the risk of PPCs across different surgical settings.Methods: We searched MEDLINE, Web of Science, Embase, the Physiotherapy Evidence Database, and the Cochrane Central Register, without language restrictions, for studies from inception to July 2020. We included randomized controlled trials that compared patients receiving exercise training with those receiving usual care or sham training before cardiac, lung, esophageal, or abdominal surgery. PPCs were the main outcome; secondary outcomes were preoperative functional changes and postoperative mortality, cardiovascular complications, and hospital length of stay. The study was registered with PROSPERO (International Prospective Register of Systematic Reviews).Results: From 29 studies, 2,070 patients were pooled for meta-analysis. Compared with the control condition, preoperative exercise training was associated with a lower incidence of PPCs (23 studies, 1,864 patients; relative risk, 0.52; 95% confidence interval [CI], 0.41 to 0.66; grading of evidence, moderate); Trial Sequential Analysis confirmed effectiveness, and there was no evidence of difference of effect across surgeries, type of training (respiratory muscles, endurance or combined), or preoperative duration of training. At the end of the preoperative period, exercise training resulted in increased peak oxygen uptake (weighted mean difference [WMD], +2 ml/kg/min; 99% CI, 0.3 to 3.7) and higher maximal inspiratory pressure (WMD, +12.2 cm H &lt;sub&gt;2&lt;/sub&gt; O; 99% CI, 6.3 to 18.2). Hospital length of stay was shortened (WMD, -2.3 d; 99% CI, -3.82 to -0.75) in the intervention group, whereas no difference was found in postoperative mortality.Conclusions: Preoperative exercise training improves physical fitness and reduces the risk of developing PPCs while minimizing hospital resources use, regardless of the type of intervention and surgery performed.Systematic review registered with https://www.crd.york.ac.uk/prospero/ (CRD 42018096956)

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Expression of phosphorylated eIF4E-binding protein 1, but not of eIF4E itself, predicts survival in male breast cancer

Background: Male breast cancer is rare and treatment is based on data from females. High expression/activity of eukaryotic initiation factor 4E (eIF4E) denotes a poor prognosis in female breast cancer, and the eIF4E pathway has been targeted therapeutically. eIF4E activity in female breast cancer is deregulated by eIF4E over-expression and by phosphorylation of its binding protein, 4E-BP1, which relieves inhibitory association between eIF4E and 4E-BP1. The relevance of the eIF4E pathway in male breast cancer is unknown. Methods: We have assessed expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 (p4E-BP1) using immunohistochemistry in a large cohort of male breast cancers (n=337) and have examined correlations with prognostic factors and survival. Results: Neither eIF4E expression or estimated eIF4E activity were associated with prognosis. However, a highly significant correlation was found between p4E-BP1 expression and disease-free survival, linking any detectable p4E-BP1 with poor survival (univariate log rank p=0.001; multivariate HR 8.8, p=0.0001). Conclusions: Our data provide no support for direct therapeutic targeting of eIF4E in male breast cancer, unlike in females. However, as p4E-BP1 gives powerful prognostic insights that are unrelated to eIF4E function, p4E-BP1 may identify male breast cancers potentially suitable for therapies directed at the upstream kinase, mTOR

ECMELLA as a bridge to heart transplantation in refractory ventricular fibrillation: A case report.

Extracorporeal membrane oxygenation (ECMO) is an effective cardiorespiratory support technique in refractory cardiac arrest (CA). In patients under veno-arterial ECMO, the use of an Impella device, a microaxial pump inserted percutaneously, is a valuable strategy through a left ventricular unloading approach. ECMELLA, a combination of ECMO with Impella, seems to be a promising method to support end-organ perfusion while unloading the left ventricle. The present case report describes the clinical course of a patient with ischemic and dilated cardiomyopathy who presented with refractory ventricular fibrillation (VF) leading to CA in the late postmyocardial infarction (MI) period, and who was successfully treated with ECMO and IMPELLA as a bridge to heart transplantation. In the case of CA on VF refractory to conventional resuscitation maneuvers, early extracorporeal cardiopulmonary resuscitation (ECPR) associated with an Impella seems to be the best strategy. It provides organ perfusion, left ventricular unloading, and ability for neurological evaluation and VF catheter ablation before allowing heart transplantation. It is the treatment of choice in cases of end-stage ischaemic cardiomyopathy and recurrent malignant arrhythmias

The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial

Background: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance. Methods/design: ACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively. All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression. Discussion: The question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Combined paclitaxel and gemcitabine as first-line treatment in metastatic non-small cell lung cancer: a multicentre phase II study

The efficacy and toxicity of combined paclitaxel and gemcitabine was evaluated in 54 chemotherapy-naive patients with metastatic non-small cell lung cancer (NSCLC). Gemcitabine i.v. 1000 mg/m2was administered on days 1 and 8 and paclitaxel 200 mg/m2as a continuous 3-hour infusion on day 1. Treatment was repeated every 21 days. Patients had a median age of 53 years. ECOG performance status was 0 or 1 in 48 patients. 41 patients (75.9%) had initial stage IV disease; histology was mainly adenocarcinoma (46.3%). 2 patients (4.3%) achieved a complete response and 15 (31.9%) achieved a partial response giving an overall response rate of 36.2% (95% CI: 22.4–49.9%); 19 patients (40.4%) had stable disease and 10 (21.3%) had progressive disease. The median survival time was 51 weeks (95% CI: 46.5–59.3), with a 1-year survival probability of 0.48 (95% CI: 0.34–0.63). Grade 3/4 neutropenia and febrile neutropenia occurred in 15.2% and 2.2% of courses, respectively. Grade 3/4 thrombocytopenia was rare (1.8% of courses). Peripheral neurotoxicity developed in 25 patients (47.2%), mostly grade 1/2. Arthalgia/myalgia was observed in 30 patients (56.6%), generally grade 1 or 2. Grade 3 abnormal levels of serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) occurred in 5 patients (9.4%) and 1 patient (1.9%), respectively. Combined paclitaxel and gemcitabine is an active and well-tolerated regimen for the treatment of advanced NSCLC, and warrants further investigation in comparative, randomized trials. © 2001 Cancer Research Campaign http://www.bjcancer.co