Quality of reporting and risk of bias:a review of randomised trials in occupational health

OBJECTIVES: To assess the reporting quality of randomisation and allocation methods in occupational health and safety (OHS) trials in relation to Consolidated Standards of Reporting Trials (CONSORT) requirements of journals, risk of bias (RoB) and publication year. METHODS: We systematically searched for randomised controlled trials (RCTs) in PubMed between 2010 and May 2019 in 18 OHS journals. We measured reporting quality as percentage compliance with the CONSORT 2010 checklist (items 8–10) and RoB with the ROB V.2.0 tool (first domain). We tested the mean difference (MD) in % in reporting quality between CONSORT-requiring and non-requiring journals, trials with low, some concern and high RoB and publications before and after 2015. RESULTS: In 135 articles reporting on 129 RCTs, average reporting quality was at 37.4% compliance (95% CI 31.9% to 43.0%), with 10% of articles reaching 100% compliance. Reporting quality was significantly better in CONSORT-requiring journals than non-requiring journals (MD 31.0% (95% CI 21.4% to 40.7%)), for studies at low RoB than high RoB (MD 33.1% (95% CI 16.1% to 50.2%)) and with RoB of some concern (MD 39.8% (95% CI 30.0% to 49.7%)). Reporting quality did not improve over time (MD −5.7% (95% CI −16.8% to 5.4%). CONCLUSIONS: Articles in CONSORT-requiring journals and of low RoB studies show better reporting quality. Low reporting quality is linked to unclear RoB judgements (some concern). Reporting quality did not improve over the last 10 years and CONSORT is insufficiently implemented. Concerted efforts by editors and authors are needed to improve CONSORT implementation

Explicit kinetic heterogeneity: mechanistic models for interpretation of labeling data of heterogeneous cell populations

Estimation of division and death rates of lymphocytes in different conditions is vital for quantitative understanding of the immune system. Deuterium, in the form of deuterated glucose or heavy water, can be used to measure rates of proliferation and death of lymphocytes in vivo. Inferring these rates from labeling and delabeling curves has been subject to considerable debate with different groups suggesting different mathematical models for that purpose. We show that the three models that are most commonly used are in fact mathematically identical and differ only in their interpretation of the estimated parameters. By extending these previous models, we here propose a more mechanistic approach for the analysis of data from deuterium labeling experiments. We construct a model of "kinetic heterogeneity" in which the total cell population consists of many sub-populations with different rates of cell turnover. In this model, for a given distribution of the rates of turnover, the predicted fraction of labeled DNA accumulated and lost can be calculated. Our model reproduces several previously made experimental observations, such as a negative correlation between the length of the labeling period and the rate at which labeled DNA is lost after label cessation. We demonstrate the reliability of the new explicit kinetic heterogeneity model by applying it to artificially generated datasets, and illustrate its usefulness by fitting experimental data. In contrast to previous models, the explicit kinetic heterogeneity model 1) provides a mechanistic way of interpreting labeling data; 2) allows for a non-exponential loss of labeled cells during delabeling, and 3) can be used to describe data with variable labeling length

Long-term work retention after treatment for cancer:a systematic review and meta-analysis

Purpose: Almost half of people diagnosed with cancer are working age. Survivors have increased risk of unemployment, but little is known about long-term work retention. This systematic review and meta-analysis assessed work retention and associated factors in long-term cancer survivors. Methods: We searched Medline/Pubmed, Embase, PsychINFO, and CINAHL for studies published 01/01/2000–08/01/2019 reporting work retention in adult cancer survivors ≥ 2 years post-diagnosis. Survivors had to be in paid work at diagnosis. Pooled prevalence of long-term work retention was estimated. Factors associated with work retention from multivariate analysis were synthesized. Results: Twenty-nine articles, reporting 21 studies/datasets including 14,207 cancer survivors, were eligible. Work retention was assessed 2–14 years post-diagnosis. Fourteen studies were cross-sectional, five were prospective, and two contained both cross-sectional and prospective elements. No studies were scored as high quality. The pooled estimate of prevalence of long-term work retention in cancer survivors working at diagnosis was 0.73 (95%CI 0.69–0.77). The proportion working at 2–2.9 years was 0.72; at 3–3.9 years 0.80; at 4–4.9 years 0.75; at 5–5.9 years 0.74; and 6+ years 0.65. Pooled estimates did not differ by cancer site, geographical area, or study design. Seven studies assessed prognostic factors for work retention: older age, receiving chemotherapy, negative health outcomes, and lack of work adjustments were associated with not working. Conclusion: Almost three-quarters of long-term cancer survivors working at diagnosis retain work. Implications for Cancer Survivors: These findings are pertinent for guidelines on cancer survivorship care. Professionals could focus support on survivors most likely to have poor long-term work outcomes

Employment and insurance outcomes and factors associated with employment among long-term thyroid cancer survivors:a population-based study from the PROFILES registry

Contains fulltext : 172452.pdf (Publisher’s version ) (Open Access)PURPOSE: To obtain insight into employment and insurance outcomes of thyroid cancer survivors and to examine the association between not having employment and other factors including quality of life. METHODS: In this cross-sectional population-based study, long-term thyroid cancer survivors from the Netherlands participated. Clinical data were collected from the cancer registry. Information on employment, insurance, socio-demographic characteristics, long-term side effects, and quality of life was collected with questionnaires. RESULTS: Of the 223 cancer survivors (response rate 87 %), 71 % were employed. Of the cancer survivors who tried to obtain insurance, 6 % reported problems with obtaining health care insurance, 62 % with life insurance, and 16 % with a mortgage. In a multivariate logistic regression analysis, higher age (OR 1.07, CI 1.02-1.11), higher level of fatigue (OR 1.07, CI 1.01-1.14), and lower educational level (OR 3.22, CI 1.46-7.09) were associated with not having employment. Employment was associated with higher quality of life. CONCLUSIONS: Many thyroid cancer survivors face problems when obtaining a life insurance, and older, fatigued, and lower educated thyroid cancer survivors may be at risk for not having employment

Preoperative and Early Postoperative Quality of Life Predict Survival in Potentially Curable Patients with Esophageal Cancer

Background: In patients with esophageal cancer, evidence for prognostic significance of preoperative quality of life (QoL) is limited, while the prognostic significance of postoperative QoL has not been investigated at all. Aim: To determine whether preoperative and postoperative QoL measurements can predict survival independently from clinical and pathological factors, in patients with potentially curable esophageal adenocarcinoma. Methods: A randomized controlled trial was performed from 1994 to 2000 in two academic medical centres, comparing transthoracic and transhiatal esophagectomy. QoL questionnaires were sent before and 3 months after surgery (Medical Outcome Study Short Form-20 and Rotterdam Symptom Checklist). Uni- and multivariate Cox regression analyses were used to examine firstly the prognostic value of preoperative QoL and several clinical factors, and secondly of postoperative QoL, several clinical factors, and pathological staging. Results: Out of 220 randomized patients, 199 participated in the QoL-study. In the multivariate preoperative model physical symptom scale (p = 0.021), tumor length (p = 0.034), and endosonographic T-stage (p = 0.003) were predictive for overall survival. In the postoperative multivariate analysis, social functioning (p = 0.035), pain (p = 0.026), and activity level (p = 0.037) predicted survival, besides pathological T-stage (p < 0.001) and N-stage (p < 0.001). Conclusion: In the present paper the first large consecutive series of potentially curable esophageal cancer patients is presented in whom prospectively collected QoL data before and after potentially curative surgical resection were used to predict survival. Both preoperative (physical symptoms) and postoperative (social functioning, pain, and activity level) QoL subscales are independent predictors of survival in potentially curable patients with esophageal adenocarcinoma

Enhancing return-to-work in cancer patients, development of an intervention and design of a randomised controlled trial

ABSTRACT: BACKGROUND: Compared to healthy controls, cancer patients have a higher risk of unemployment, which has negative social and economic impacts on the patients and on society at large. Therefore, return-to-work of cancer patients needs to be improved by way of an intervention. The objective is to describe the development and content of a work-directed intervention to enhance return-to-work in cancer patients and to explain the study design used for evaluating the effectiveness of the intervention. METHODS: Development and content of the intervention The work-directed intervention has been developed based on a systematic literature review of work-directed interventions for cancer patients, factors reported by cancer survivors as helping or hindering their return-to-work, focus group and interview data for cancer patients, health care professionals, and supervisors, and vocational rehabilitation literature. The work-directed intervention consists of: 1) 4 meetings with a nurse at the treating hospital department to start early vocational rehabilitation, 2) 1 meeting with the participant, occupational physician, and supervisor to make a return-to-work plan, and 3) letters from the treating physician to the occupational physician to enhance communication. Study design to evaluate the intervention The treating physician or nurse recruits patients before the start of initial treatment. Patients are eligible when they have a primary diagnosis of cancer, will be treated with curative intent, are employed at the time of diagnosis, are on sick leave, and are between 18 and 60 years old. After the patients have given informed consent and have filled out a baseline questionnaire, they are randomised to either the control group or to the intervention group and receive either care as usual or the work-directed intervention, respectively. Primary outcomes are return-to-work and quality of life. The feasibility of the intervention and direct and indirect costs will be determined. Outcomes will be assessed by a questionnaire at baseline and at 6, 12, 18, and 24 months after baseline. DISCUSSION: This study will provide information about the effectiveness of a work-directed intervention for cancer patients. The intention is to implement the intervention in normal care if it has been shown effective. Trial registration: NTR165

Natriuretic peptides and integrated risk assessment for cardiovascular disease. an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention

Alu-repeat–induced deletions within the NCF2 gene causing p67- phox –deficient chronic granulomatous disease (CGD)

Mutations that impair expression or function of the components of the phagocyte NADPH oxidase complex cause chronic granulomatous disease (CGD), which is associated with life-threatening infections and dysregulated granulomatous inflammation. In five CGD patients from four consanguineous families of two different ethnic backgrounds, we found similar genomic homozygous deletions of 1,380 bp comprising exon 5 of NCF2 , which could be traced to Alu-mediated recombination events. cDNA sequencing showed in-frame deletions of phase zero exon 5, which encodes one of the tandem repeat motifs in the tetratricopeptide (TPR4) domain of p67- phox . The resulting shortened protein (p67Δ5) had a 10-fold reduced intracellular half-life and was unable to form a functional NADPH oxidase complex. No dominant negative inhibition of oxidase activity by p67Δ5 was observed. We conclude that Alu-induced deletion of the TPR4 domain of p67- phox leads to loss of function and accelerated degradation of the protein, and thus represents a new mechanism causing p67- phox –deficient CGD. Hum Mutat 30:1–8, 2009. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64904/1/21156_ftp.pd

Impact of Positive Lymph Nodes and Resection Margin Status on the Overall Survival of Patients with Resected Perihilar Cholangiocarcinoma: The ENSCCA Registry

Background: Lymph node metastasis and positive resection margins have been reported to be major determinants of overall survival (OS) and poor recurrence-free survival (RFS) for patients who underwent resection for perihilar cholangiocarcinoma (pCCA). However, the prognostic value of positive lymph nodes independently from resection margin status on OS has not been evaluated. Methods: From the European Cholangiocarcinoma (ENSCCA) registry, patients who underwent resection for pCCA between 1994 and 2021 were included in this retrospective cohort study. The primary outcome was OS stratified for resection margin and lymph node status. The secondary outcome was recurrence-free survival. Results: A total of 325 patients from 11 different centers and six European countries were included. Of these, 194 (59.7%) patients had negative resection margins. In 113 (34.8%) patients, positive lymph nodes were found. Lymph node status, histological grade, and ECOG performance status were independent prognostic factors for survival. The median OS for N0R0, N0R1, N+R0, and N+R1 was 38, 30, 18, and 12 months, respectively (p < 0.001). Conclusion: These data indicate that in the presence of positive regional lymph nodes, resection margin status does not determine OS or RFS in patients with pCCA. Achieving negative margins in patients with positive nodes should not come at the expense of more extensive surgery and associated higher mortality.The ENSCCA Registry is completely funded by the European Association for the Study of the Liver (EASL; Registry grant awards 2016 and 2019 to J.M.B.), Incyte Bioscience International Sàrl (grant award 2020 to J.M.B.) and European Union’s Horizon 2020 Research and Innovation Program (grant number 825510, ESCALON: to J.M.B. and A.L.)