Operational leeway in work situations: do ergonomic risk assessment tools consider operational leeway for job analysis?

Our study shows that information on operational leeway is limited in the originator articles of the ergonomic risk assessment tools for prevention of musculoskeletal disorders (MSDs). The tools' underlying theoretical models do not consider the indicators of operational leeway, and they cannot determine the sufficiency of the situational operational leeway in a work situation. Consequently, regulation of the activity, which ensures the performance goals and the individual's health, has been overlooked. The lack of literature on indicators of situational operational leeway is one of the reasons for this deficit. Defining the indicators for this concept would be an innovation in the approach of MSD risk prevention. Developing empirically the concept of situational operational leeway in risk assessment tools would help to progress the current approach of MSD prevention. This study therefore proposes indicators of situational operational leeway to increase the representativeness and reliability of the risk assessment tools for MSDs.

Comparison of three methods for evaluation of work postures in a truck assembly plant.

This study compared the results of three risk assessment tools (self-reported questionnaire, observational tool, direct measurement method) for the upper limbs and back in a truck assembly plant at two cycle times (11 and 8 min). The weighted Kappa factor showed fair agreement between the observational and direct measurement method for the arm (0.39) and back (0.47). The weighted Kappa factor for these methods was poor for the neck (0) and wrist (0) but the observed proportional agreement (Po) was 0.78 for the neck and 0.83 for the wrist. The weighted Kappa factor between questionnaire and direct measurement showed poor or slight agreement (0) for different body segments in both cycle times. The results revealed moderate agreement between the observational tool and the direct measurement method, and poor agreement between the self-reported questionnaire and direct measurement. Practitioner Summary: This study provides risk exposure measurement by different common ergonomic methods in the field. The results help to develop valid measurements and improve exposure evaluation. Hence, the ergonomist/practitioners should apply the methods with caution, or at least knowing what the issues/errors are.

A comparison of neck bending and flexion measurement methods for assessment of ergonomic risk.

Head movements of workers were measured in the sagittal plane in order to establish a precise and accurate assessment method to be used in real work situations. Measurements were performed using two inclinometers connected to an embedded recording system. Two quantitative analysis methods were tested, i.e., measurement of bending with an inclinometer attached to the head, and measurement of flexion/extension by using an additional inclinometer located at C7/T1. The results were also compared with a video observation method (qualitative). The results showed that bending measurements were significantly different from those of flexion/extension for angles between 0° and 20°, and angles >45°. There were also significant differences between workers for flexion >45°, reflecting individual variability. Additionally, several limitations of observational methods were revealed by this study.

Risk factors for carpal tunnel syndrome related to the work organization: a prospective surveillance study in a large working population.

The study aimed to determine the risk factors for incident carpal tunnel syndrome (CTS) in a large working population, with a special focus on factors related to work organization. In 2002-2005, 3710 workers were assessed and, in 2007-2010, 1611 were re-examined. At baseline all completed a self-administered questionnaire about personal/medical factors and work exposure. CTS symptoms and physical examination signs were assessed by a standardized medical examination at baseline and follow-up. The risk of "symptomatic CTS" was higher for women (OR = 2.9 [1.7-5.2]) and increased linearly with age (OR = 1.04 [1.00-1.07] for 1-year increment). Two work organizational factors remained in the multivariate risk model after adjustment for the personal/medical and biomechanical factors: payment on a piecework basis (OR = 2.0, 95% CI 1.1-3.5) and work pace dependent on automatic rate (OR = 1.9, 95% CI 0.9-4.1). Several factors related to work organization were associated with incident CTS after adjustment for potential confounders.

FOLFIRI® and bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms.

BACKGROUND: Over 50% of colorectal cancer (CRC) patients develop metastases. The aim of this study was to evaluate efficacy and tolerance of first-line FOLFIRI® + bevacizumab (B) treatment for metastatic CRC, and to assess genetic polymorphisms as potential markers. METHODS: Adult patients with histologically-proven, non-resectable metastatic CRC and ECOG ≤ 2 were included. 14-day cycles consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m2), bolus FU (400 mg/m2) and leucovorin (400 mg/m2), followed by 46-hour FU infusions (2400 mg/m2). Primary endpoint was response rate according to RECIST criteria. Secondary endpoints were overall (OS) and progression-free (PFS) survivals, response duration, and toxicity. Associations between clinical data, UGT1A1, thymidylate synthase, VEGFA polymorphisms and PFS, OS and toxicity were analyzed. RESULTS: Sixty-two patients were enrolled (median age 68y). 59/62 patients were eligible and evaluable for response at 6 months: 28 showed partial response (47.5%; 95% CI; 34.3-60.9), 20 stable disease (33.9%) and 11 progression (18.6%). Grade 3/4 toxicities were as follows: neutropenia 16.1%; diarrhea 11.3%; nausea-vomiting 1.6%. Median response duration was 9.5 months (range 2.7-20); median PFS 10.3 months (range 8.8-11.7); and median OS 25.7 months (range 20.2-29.7). 11/59 initially unresectable patients were resectable after treatment. VEGFA polymorphism (rs25648) was associated with better OS (HR: 3.61; 95% CI: 1.57-8.30). CONCLUSIONS: FOLFIRI® + bevacizumab is active with good response rate, long median OS, and a good safety profile. A VEGFA polymorphism might have a prognostic value in this malignancy. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00467142 (registration date: April 25, 2007).

Absence of transcriptomic signature of response to chemotherapy in metastatic colorectal carcinoma patients.

AIM: Tumor gene-expression profiling may define signatures capable of discriminating between responders and nonresponders to chemotherapy. PATIENTS & METHODS: Fifty seven metastatic colorectal cancer patients were prospectively included and 40 tumors were analyzed. Patients were treated in first line with 5-fluorouracil associated with irinotecan or oxaliplatin. Response was evaluated using WHO criteria every 2 months after chemotherapy. Gene-expression profiling was performed using Applied Biosystems microarrays (Human Genome Survey Microarray v2.0; Paris, France). Data were analyzed using Bioconductor packages. Differential-expression analysis was performed by fitting a linear model. Moderated t-statistics were computed and p-values were adjusted for false-discovery rate. Pearson correlations tests were evaluated between gene expression and progression-free and overall survival. RESULTS: Nonsupervised analysis did not show any clustering of expression levels according to treatment response. Supervised analysis compared expression levels between responders and nonresponders, within each treatment group and independently from treatment. No genes were identified as differentially expressed at a p-value of 10(-3) and false-discovery rate of 30%. No correlation between expression levels and survival data was found. CONCLUSION: These negative results show that the determinants of response to chemotherapy should be sought not only in the tumor characteristics, but also among the processes leading to drug availability to the tumor.

Evaluation of efficacy and safety of FOLFIRI for elderly patients with gastric cancer: a first-line phase II study.

OBJECTIVE: Current chemotherapy protocols for gastric cancer present high toxicity. The FOLFIRI regimen has shown promising results with elderly colorectal cancer patients and for gastric cancer patients but this is the first report on elderly gastric cancer patients. DESIGN: In this multicenter non-randomized phase II trial, we administered the FOLFIRI chemotherapy protocol (irinotecan [180 mg/m(2)], fluorouracil [5-FU] [400 mg/m(2)] and folinic acid 400 mg/m(2) or 200mg/m(2) of l-folinic acid) to patients aged over 70 years with locally-advanced or metastatic gastric cancer combined with Comprehensive Geriatric Assessment (CGA). Responses were assessed at 2 months. RESULTS: Forty-two patients received eight cycles of the FOLFIRI regimen, with 82.5% of patients showing disease control: 10 patients (26%) showing objective (partial or complete) responses and 23 (57.5%) showing stable disease. One-year overall survival (OS) was 41.5% [95%CI 26.5-56.0] and one-year progression-free survival (PFS) was 31.8% [95%CI 18.4-46.1%]. We observed 10 Grade 3/4 hematologic toxicities with one febrile neutropenia. CGA data demonstrated that geriatric functions were not altered by treatment and that nutritional status improved over treatment. CONCLUSIONS: Results show excellent disease control and relatively high survival rates with limited toxicity similar to younger patients indicating that this regimen should be considered as a possible treatment in advanced gastric cancer of the elderly.

KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: biological and clinical implications.

BACKGROUND: KRAS and BRAF mutations in primary colorectal tumors (PT) are predictive of nonresponse to anti-epidermal growth factor receptor (EGFR) antibodies in patients with metastatic colorectal cancer (mCRC). The question of primary resistance to anti-EGFR treatment as a result of the presence of KRAS or BRAF mutations only in metastases has been raised but not resolved. METHODS: We analyzed the mutational status of KRAS and BRAF in 64 new patients with mCRC and performed a systematic review of published data from 285 patients. RESULTS: A total of 285 and 95 matched PT/metastases were available for the analysis of the KRAS and the BRAF status, respectively. An identical mutational pattern of KRAS in PT and the matching metastases were reported in all the cases but 14 (5%). In six cases (2%), KRAS was mutated in the PT and wild type in the metastatic site, whereas in eight cases (3%), KRAS was wild type in the PT and mutated in the metastatic site. An identical mutational pattern of BRAF in PT and the matching metastases was reported in all but two cases (3%). In one case (1.5%), BRAF was mutated in the PT and wild type in the metastatic site, whereas in one case (1.5%), BRAF was wild type in the PT and mutated in the metastatic site. CONCLUSIONS: The acquisition by metastases of a KRAS or a BRAF mutation that was not present in the PT is a rare event, occurring in 5% of cases of mCRC. This is not a frequent mechanism of primary resistance to anti-EGFR treatments in mCRC.

Could bipolar vessel sealers prevent bile leaks after hepatectomy?

BACKGROUND AND AIMS: The aim of this work was to test the feasibility of using a bipolar low thermal acting system inducing collagenic sealing but not protein coagulation to secure hepatic parenchyma cutting. MATERIALS AND METHODS: Thirty consecutive hepatectomies were carried out using kellyclasy plus ligatures and clips (controls), while the following 50 hepatectomies used kellyclasy plus bipolar vessels sealer (BVS). Blood loss, duration of hepatic pedicle clamping, length of hospital stay, and complications were recorded. RESULTS: There was no statistically significant difference in blood loss and duration of clamping between controls and BVS. Specific complications (9/21 in the control group vs 1/49 for the BVS group, p<0.00045) and length of hospital stay (14 days in the control group vs 11 days in the BVS group, p<0.014) were statistically lower in BVS group than in the controls, mainly due to prevention of bile duct leakages. CONCLUSIONS: Our data suggest that BVS may be particularly efficient to achieve bilistasis leading to the highest level of safety in performing hepatectomies. Further studies are now needed to confirm its superiority on the classical biliary ducts occlusion techniques.

Capecitabine/oxaliplatin, a safe and active first-line regimen for older patients with metastatic colorectal cancer: post hoc analysis of a large phase II study.

PURPOSE: The tumor-activated fluoropyrimidine capecitabine achieves response rates superior to those of bolus 5-fluorouracil/leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer (CRC), with favorable safety and fewer hospitalizations. Capecitabine is also at least as effective as bolus 5-FU/LV in the adjuvant setting, again with a favorable safety profile. Improved outcomes with capecitabine versus bolus 5-FU/LV in the adjuvant setting have been shown in overall trial populations and in patients aged >or= 70 years. Capecitabine/oxaliplatin (XelOx) is a safe and active combination for the first-line treatment of metastatic CRC. PATIENTS AND METHODS: This post hoc analysis of a large phase II trial compared data from older and younger patients treated with first-line XelOx: oxaliplatin 130 mg/m(2) intravenously on day 1 followed by oral capecitabine 1,000 mg/m(2) twice daily for 14 days every 3 weeks. RESULTS: The median age of the overall population (N = 96) was 64 years (range, 34-79 years), including 52 younger patients (< 65 years of age) and 44 older patients (>or= 65 years of age). Both age groups received a median of 8 cycles (range, 1-26 cycles) of XelOx. The XelOx regimen had similar high activity in both groups, with response rates of 58% (95% CI, 43%-71%) and 52% (95% CI, 37%-68%) in younger and older patients, respectively. In addition, time to disease progression and overall survival were similar in both groups (P > 0.5 for both outcomes). The XelOx regimen also had a favorable safety profile, with no clinically relevant differences between older and younger patients. The overall incidence of adverse events (including grade 3/4), dose reductions, and withdrawals because of adverse events were similar in both groups. CONCLUSION: In the context of an aging population, XelOx provides a highly effective and tolerable first-line treatment for patients with metastatic CRC.

Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas.

BACKGROUND: The use of chemoradiotherapy for pancreatic cancer has been advocated for its potential ability to downstage locally advanced tumors. This article reports our experience with chemoradiotherapy for patients with unresectable, locally advanced pancreatic cancer (superior mesenteric artery or celiac axis encasement). STUDY DESIGN: Since 1998, 61 patients with radiographically unresectable, pathologically confirmed pancreatic adenocarcinoma have received standard fractionation radiation therapy (total dose, 45 Gy at 1.8 Gy, 5 d/wk) with chemotherapy, which included a continuous infusion of fluorouracil (5-FU: 650 mg/m(2)/D1-D5 and D21-D25) and cisplatin (80 mg/m(2)/bolus D2 and D22). Patients with tumor response at restaging CT scan underwent surgical exploration to determine whether the tumor was resectable. RESULTS: Thirty-eight of 61 (62%) restaged patients demonstrated a disease progression. Twenty-three patients (38%) had an objective response, with, in all cases, persistence of arterial encasement. Twenty-three patients underwent exploratory operations after chemoradiotherapy, and 13 underwent standard Whipple resection. So 13 of 23 (56%) patients who had exploratory operation, or 23 of 61 (21%) patients, underwent surgical resection. With a median followup of 27 months, median survival for the resected patients was 28 months. Median survival was 11 months in the nonresponder group (n = 38) and 20 months in the group who received a palliative procedure (n = 10). CONCLUSIONS: Locally advanced, unresectable pancreatic adenocarcinoma may be downstaged by chemoradiotherapy to allow for surgical resection. Patients whose cancer becomes resectable have a median survival at least comparable with survival after resection for initially resectable pancreatic adenocarcinoma.

XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer.

PURPOSE: Capecitabine has demonstrated high efficacy as first-line treatment for metastatic colorectal cancer (MCRC). Oxaliplatin shows synergy with fluorouracil (FU), with little toxicity overlap. The XELOX regimen (capecitabine plus oxaliplatin), established in a previous dose-finding study, should improve on infused oxaliplatin with FU and leucovorin (FOLFOX) regimens. The present studies further characterize efficacy and safety of the XELOX regimen. PATIENTS AND METHODS: The antitumor activity of XELOX was investigated in a colon cancer xenograft model. Patients with MCRC received first-line XELOX in 3-week treatment cycles: intravenous oxaliplatin 130 mg/m(2) (day 1) followed by oral capecitabine 1,000 mg/m(2) twice daily (day 1, evening, to day 15, morning). RESULTS: A preclinical study confirmed that capecitabine has supra-additive activity with oxaliplatin. In the clinical study, 53 of 96 patients (55%) achieved an objective response, and 30 (31%) experienced disease stabilization for >/= 3 months following treatment. After 24 months' minimum follow-up, median time to disease progression (TTP) and median overall survival were 7.7 and 19.5 months, respectively. XELOX safety was predictable and similar to the FOLFOX4 regimen, except that myelosuppression was uncommon with XELOX (grade 3 or 4 neutropenia, 7%). Most adverse events were mild to moderate, the most common being acute sensory neuropathy (85%). Sixty-day, all-cause mortality was 2%. CONCLUSION: XELOX is a highly effective first-line treatment for MCRC. Response rates, TTP, and overall survival are similar to those observed with FU/leucovorin/oxaliplatin combinations. XELOX provides a more convenient regimen, likely to be preferred by both patients and healthcare providers. Capecitabine has the potential to replace FU/LV in combination with oxaliplatin for MCRC.

Pharmacokinetic linearity of i.v. vinorelbine from an intra-patient dose escalation study design.

As pharmacokinetics represents a bridge between pharmacological concentrations and clinical regimens, the pharmacokinetic exploration of the therapeutic dose range is a major outcome. This study was aimed at assessing pharmacokinetic linearity of i.v. vinorelbine through an open design with intra-patient dose escalation (3 doses/group). Three groups of six patients received either 20-25-30 mg/m2; or 25-30-35 mg/m2; or 30-35-40 mg/m2. The inclusion criteria were: histologically confirmed tumour with at least one assessable target lesion, age 25-75 years, WHO PS < or =2, normal haematology and biochemistry, life expectancy > or =3 months. The pharmacokinetics was evaluated in both whole blood and plasma over 120 h. Twenty-six patients were recruited and 18 were evaluable for pharmacokinetics. The toxicity consisted in grade < or =3 leucopenia and neutropenia (<20% of courses) and two grade 4 constipation with rapid recovery (2/54 courses). Compared to blood, plasma was demonstrated to underestimate the pharmacokinetic parameters. In blood, the drug total clearance was about 0.6 l/h/kg, with minor contribution of renal clearance, steady state volume of distribution close to 13 l/h/kg, and elimination half-life at about 40 h. A pharmacokinetic linearity was demonstrated up to 40 mg/m2, and even up to 45 mg/m2 when pooling data from another study. A pharmacokinetic-pharmacodynamic relationship was evidenced on leucopenia and neutropenia when pooling the data from the two studies.