Miracle-dz/UniFAR-FTUs huggingface dataset:
Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia.

PURPOSE Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition. Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose- and schedule-optimization study is reported. PATIENTS AND METHODS In this open-label phase III trial, 670 patients with imatinib-resistant or -intolerant CP-CML were randomly assigned 1:1:1:1 between four dasatinib treatment groups: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. RESULTS With minimum follow-up of 6 months (median treatment duration, 8 months; range, < 1 to 15 months), marked and comparable hematologic (complete, 86% to 92%) and cytogenetic (major, 54% to 59%; complete, 41% to 45%) response rates were observed across the four groups. Time to and duration of cytogenetic response were similar, as was progression-free survival (8% to 11% of patients experienced disease progression or died). Compared with the approved 70-mg twice-daily regimen, dasatinib 100 mg once daily resulted in significantly lower rates of pleural effusion (all grades, 7% v 16%; P = .024) and grade 3 to 4 thrombocytopenia (22% v 37%; P = .004), and fewer patients required dose interruption (51% v 68%), reduction (30% v 55%), or discontinuation (16% v 23%). CONCLUSION Dasatinib 100 mg once daily retains the efficacy of 70 mg twice daily with less toxicity. Intermittent target inhibition with tyrosine kinase inhibitors may preserve efficacy and reduce adverse events.
Individual physician practice variation in hematopoietic cell transplantation.

PURPOSE Previous studies have evaluated practice variation in hematopoietic cell transplantation (HCT) among transplant centers and countries. There are no studies investigating individual physician practice variation in HCT. METHODS An international Internet-based survey of transplant physicians collected data on medical decisions made by adult and pediatric HCT physicians. Multivariable analyses identified practitioner and transplant center characteristics predictive of medical decision making. RESULTS Analysis of 526 assessable respondents showed a wide variation in management approaches to specific clinical scenarios. Pediatric and adult transplant physicians differed significantly in their management strategies for chronic myeloid leukemia, acute and chronic graft-versus-host disease, and choice of graft source for patients with aplastic anemia. Among adult transplant physicians, there was little agreement on the patient factors favoring reduced intensity conditioning or myeloablative conditioning. CONCLUSION These results emphasize the heterogeneity of worldwide transplant practices. Local preferences or biases likely result in similar patients being offered different transplant and treatment procedures. The degree of practice variation also highlights the need for clinical trials to clarify areas of controversy. Where clinical trials are not feasible, data from observational studies may be the best available evidence to guide practice.
Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27.

PURPOSE National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-18 was designed to determine whether four cycles of doxorubicin and cyclophosphamide (AC) administered preoperatively improved breast cancer disease-free survival (DFS) and overall survival (OS) compared with AC administered postoperatively. Protocol B-27 was designed to determine the effect of adding docetaxel (T) to preoperative AC on tumor response rates, DFS, and OS. PATIENTS AND METHODS Analyses were limited to eligible patients. In B-18, 751 patients were assigned to receive preoperative AC, and 742 patients were assigned to receive postoperative AC. In B-27, 784 patients were assigned to receive preoperative AC followed by surgery, 783 patients were assigned to AC followed by T and surgery, and 777 patients were assigned to AC followed by surgery and then T. RESULTS Results from B-18 show no statistically significant differences in DFS and OS between the two groups. However, there were trends in favor of preoperative chemotherapy for DFS and OS in women less than 50 years old (hazard ratio [HR] = 0.85, P = .09 for DFS; HR = 0.81, P = .06 for OS). DFS conditional on being event free for 5 years also demonstrated a strong trend in favor of the preoperative group (HR = 0.81, P = .053). Protocol B-27 results demonstrated that the addition of T to AC did not significantly impact DFS or OS. Preoperative T added to AC significantly increased the proportion of patients having pathologic complete responses (pCRs) compared with preoperative AC alone (26% v 13%, respectively; P < .0001). In both studies, patients who achieved a pCR continue to have significantly superior DFS and OS outcomes compared with patients who did not. CONCLUSION B-18 and B-27 demonstrate that preoperative therapy is equivalent to adjuvant therapy. B-27 also showed that the addition of preoperative taxanes to AC improves response.
Phase I trial of the human immunodeficiency virus protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer.

PURPOSE Preclinically, HIV protease inhibitors radiosensitize tumors with activated PI3-kinase/Akt pathway. We determined the toxicity of nelfinavir chemoradiotherapy in borderline resectable and unresectable pancreatic cancer. PATIENTS AND METHODS Oral nelfinavir (2 x 1,250 mg) was started 3 days before and continued throughout chemoradiotherapy to 50.4 Gy (boost, 59.4 Gy) in 12 patients. Two gemcitabine dose levels (DL) were tested (200 mg/m(2) and 300 mg/m(2) on days 1, 8, 22, and 29). Cisplatin was administered on the same days at 30 mg/m(2). Phospho-Akt downregulation by nelfinavir was monitored by immunoblotting in patient leukocytes. Restaging positron emission tomography (PET)/computed tomography (CT) and CA19-9 levels served to assess response, and responding tumors were resected. RESULTS At each DL, five of six patients completed chemoradiotherapy, and two of 12 patients had incomplete chemoradiotherapy because of clinical depression (DL1) and peritoneal metastasis (DL2). Grade 4 toxicities were a transaminase elevation (DL2) as a result of biliary stent occlusion and acute cholecystitis as a result of peritoneal metastasis (DL2). Stent occlusions led to dose-limiting toxicities of grade 3 liver enzyme and bilirubin elevations (two patients at DL1, one patient at DL2). Grade 3 nausea and vomiting occurred in a DL2 patient, and weight loss occurred in a DL1 patient who refused supportive feeding. Secondary complete resection was possible in six of 10 patients with complete chemoradiotherapy, including one tumor with pathologic sterilization. Partial CT responses were observed in five of 10 patients who completed chemoradiotherapy. Of nine patients assessable by PET,responses were complete in five patients and partial patients, and stable disease was observed in two patients. CONCLUSION The combination of nelfinavir and chemoradiotherapy showed acceptable toxicity and promising activity in patients with pancreatic cancer.
A comparison of exposure assessment approaches: lung cancer and occupational asbestos exposure in a population-based case–control study

Objectives In attempts to overcome the limitations of self-reported data in occupational health research, job-exposure matrices, which assign exposure by occupation, have emerged as an objective approach for assessing occupational exposures. On the basis of a lung cancer case–control study conducted in the Greater Toronto Area, 1997–2002, assessment of occupational exposure to asbestos was compared using self-reports and a general population job-exposure matrix (DOM-JEM). Methods Cases and frequency matched controls provided life-time job histories and self-reported exposures to potential lung carcinogens including asbestos through a detailed questionnaire. Exposure to asbestos was also assigned to each job by linking occupational histories with DOM-JEM. Agreement in classification of exposed and unexposed jobs according to self-reports and DOM-JEM was evaluated using Cohen's κ. Risks for lung cancer were estimated using unconditional logistic regression for each exposure assessment approach. Results The prevalence of occupational asbestos exposure was greater when based on DOM-JEM than when based on self-reports. Agreement in classifying exposure to jobs between the two assessment approaches was poor. The risk of lung cancer was not elevated among workers who self-reported asbestos exposure, whereas workers considered exposed on the basis of DOM-JEM were almost twice as likely as unexposed workers to be diagnosed with lung cancer (OR 1.9, 95% CI 1.3 to 2.7). Conclusions It is generally assumed by epidemiologists that self-reported exposure assessments result in inflated risk estimates. In this study, self-reports found no association with a well-established risk factor, whereas a high-quality job-exposure matrix revealed relative risk estimates that are more consistent with previous findings.
The health effects of employment

A large body of research has accumulated about the health effects of the occurrence of and exposure to unemployment, projecting these events and episodes as being stressful. Hence, logically, resuming employment can be assumed to be a process that, although accompanied by a wide variety of work-related physical and psychosocial risks, is predominantly positive and enhances well-being and health. Questions as to whether this is in fact the case have generated a considerable body of longitudinal studies and also enabled meta-analyses as reported in the review by van der Noordt et al . 1 The carefully conducted and clearly reported review provides convincing evidence of the beneficial effects of employment on mental health and demonstrates the knowledge gap as regards the effects on somatic health and mortality. Moreover, the review gives an impetus for elaborations with respect to further studies. There are four topics of particular relevance. First, the enduring depression that began at the downturn of the global economy in the late 2000s has revived scholars from the end of the past millennium who were predicting the emergence of a postmodern, less work-based, social order in the Western world,2 even …
The effect of lifting during work on low back pain: a health impact assessment based on a meta-analysis

Lifting at work is considered an important risk factor for low back pain (LBP). However, contradictory findings have been reported, partly because frequency, duration and intensity (ie, the weight of the load) of lifting have not been systematically considered. This has hampered developments of threshold values for lifting. The aims of this study were: to assess the effect of lifting during work (quantified in duration, frequency or intensity) on the incidence of LBP and to quantify the impact of these relationships on the occurrence of LBP in occupational populations exposed to lifting. We searched in PubMed and EMBASE.com for longitudinal studies assessing the effect of occupational lifting on LBP incidence. For each study, the exposure–response slope of the association was estimated by loglinear regression analysis. When possible, a meta-analysis on these slopes was conducted. In a health impact assessment, the effects of the pooled exposure–response relationships on LBP incidence was assessed. Eight longitudinal studies were included. Pooled estimates resulted in ORs of 1.11 (1.05 to 1.18) per 10 kg lifted and 1.09 (1.03 to 1.15) per 10 lifts/day. Duration of lifting could not be pooled. Using these ORs, we estimated that lifting loads over 25 kg and lifting at a frequency of over 25 lifts/day will increase the annual incidence of LBP by 4.32% and 3.50%, respectively, compared to the incidence of not being exposed to lifting. Intensity and frequency of lifting significantly predict the occurrence of LBP. Exposure–response relationships show that lifting heavy loads may have a substantial impact on musculoskeletal health of the working population. This information may direct the development of occupational lifting guidelines and workplace design for LBP prevention.
Effect of summer outdoor temperatures on work-related injuries in Quebec (Canada)

Objective To quantify the associations between occupational injury compensations and exposure to summer outdoor temperatures in Quebec (Canada). Methods The relationship between 374 078 injuries compensated by the Workers’ Compensation Board (WCB) (between May and September, 2003–2010) and maximum daily outdoor temperatures was modelled using generalised linear models with negative binomial distributions. Pooled effect sizes for all 16 health regions of Quebec were estimated with random-effect models for meta-analyses for all compensations and by sex, age group, mechanism of injury, industrial sector and occupations (manual vs other) within each sector. Time lags and cumulative effect of temperatures were also explored. Results The relationship between daily counts of compensations and maximum daily temperatures reached statistical significance for three health regions. The incidence rate ratio (IRR) of daily compensations per 1°C increase was 1.002 (95% CI 1.002 to 1.003) for all health regions combined. Statistically significant positive associations were observed for men, workers aged less than 45 years, various industrial sectors with both indoor and outdoor activities, and for slips/trips/falls, contact with object/equipment and exposure to harmful substances/environment. Manual occupations were not systematically at higher risk than non-manual and mixed ones. Conclusions This study is the first to quantify the association between work-related injury compensations and exposure to summer temperatures according to physical demands of the occupation and this warrants further investigations. In the context of global warming, results can be used to estimate future impacts of summer outdoor temperatures on workers, as well as to plan preventive interventions.
Distance education is as effective as traditional education when teaching food safety

A food safety and sanitation course was developed and administered using two different educational methods: traditional classroom style and distance education via CD-ROM and the Internet. A research project studied the differences between participants taking the distance education course and those taking the traditional course. Success of the participants was evaluated using several different measures: comparison of pre-/post-test, pass/fail of a United States nationally recognized food safety examination, and test score of the United States national food safety examination. Fifty individuals participated in the study: n = 22 in the traditional group and n = 28 in the distance education group. Data were analyzed using Statistical Power for the Social Sciences (SPSS). All participants took the nationally recognized food safety examination. Bivariate analyses revealed no significant association between the method of education and the national examination score. The data indicate that more highly educated people may choose a distance education course. Number of years employed in food service significantly influenced test scores among all participants. Distance participants who passed spent more time using the CD-ROM (57% spent > 10 h) compared to those who failed (25% spent > 10 h). The audio and Internet components were more useful to those who passed. Participants who passed in both groups were more likely to list English as their primary language (100%). Of those who failed, 26% listed a language other than English as primary. Data indicate that distance education is a viable method of training food service professionals in food safety and sanitation. The Distance Education Course is available through the University of Connecticut and may be accessed at http://www.team. uconn.edu/foodsafety_course/index.htm. Distance education courses in food safety are available in English, Spanish, and Vietnamese. The project was funded in part by a United States Department of Agriculture Integrated Food Safety Grant.
Occupational asthma to fish

Allergic responses to a variety of seafood have been described, including fish.1–6 We report the evaluation of a 31-year-old worker who developed occupational asthma following exposure to sole fish ( Yellowfin sole ). She had been working in a restaurant's kitchen, cooking different types of products including fish, most often sole. In the last 3 years, this worker had developed erythema and pruritus of the hands and forearms while she was manipulating fishes such as sole. In the month before being assessed at our Centre, she had increasing symptoms of dyspnoea, chest tightness and wheezing when she was exposed to cooking fumes from sole fish. …
Renal Transplantation for Patients 60 Years of Age or Older A Single‐Institution Experience

ObjectiveThe authors reviewed renal transplant outcomes in recipients 60 years of age or older. BackgroundBefore cyclosporine, patients older than 45 years of age were considered to be at high risk for transplantation. With cyclosporine, the age limits for transplantation have expanded. MethodsThe authors compared patient and graft survival, hospital stay, the incidence of rejection and rehospitalization, and the cause of graft loss for primary kidney recipients 60 years of age or older versus those 18 to 59 years of age. For those patients ≥ 60 years transplanted since 1985, the authors analyzed pretransplant extrarenal disease and its impact on post-transplant outcome. In addition, all surviving recipients ≥ 60 years completed a medical outcome survey (SF-36). ResultsPatient and graft survival for those ≥ 60 years of age versus those 18 to 59 years of age were similar 3 years after transplant. Subsequently, mortality increased for the older recipients. Death-censored graft survival was identical in the two groups. There were no differences in the cause of graft loss. Those 60 years of age or older had a longer initial hospitalization, but had fewer rejection episodes and fewer rehospitalizations. Quality of life for recipients 60 years of age or older was similar to the age-matched U.S. population. ConclusionRenal transplantation is successful for recipients 60 years of age or older. Most of them had extrarenal disease at the time of transplantation; however, extrarenal disease was not an important predictor of outcome and should not be used as an exclusion criterion. Post-transplant quality of life is excellent.
Trends in incidence of occupational asthma, contact dermatitis, noise-induced hearing loss, carpal tunnel syndrome and upper limb musculoskeletal disorders in European countries from 2000 to 2012

Objectives The European Union (EU) strategy for health and safety at work underlines the need to reduce the incidence of occupational diseases (OD), but European statistics to evaluate this common goal are scarce. We aim to estimate and compare changes in incidence over time for occupational asthma, contact dermatitis, noise-induced hearing loss (NIHL), carpal tunnel syndrome (CTS) and upper limb musculoskeletal disorders across 10 European countries. Methods OD surveillance systems that potentially reflected nationally representative trends in incidence within Belgium, the Czech Republic, Finland, France, Italy, the Netherlands, Norway, Spain, Switzerland and the UK provided data. Case counts were analysed using a negative binomial regression model with year as the main covariate. Many systems collected data from networks of ‘centres’, requiring the use of a multilevel negative binomial model. Some models made allowance for changes in compensation or reporting rules. Results Reports of contact dermatitis and asthma, conditions with shorter time between exposure to causal substances and OD, were consistently declining with only a few exceptions. For OD with physical causal exposures there was more variation between countries. Reported NIHL was increasing in Belgium, Spain, Switzerland and the Netherlands and decreasing elsewhere. Trends in CTS and upper limb musculoskeletal disorders varied widely within and between countries. Conclusions This is the first direct comparison of trends in OD within Europe and is consistent with a positive impact of European initiatives addressing exposures relevant to asthma and contact dermatitis. Taking a more flexible approach allowed comparisons of surveillance data between and within countries without harmonisation of data collection methods.
Asthma history, job type and job changes among US nurses

Objectives Nurses are at increased risk of occupational asthma, an observation that may be related to disinfectants exposure. Whether asthma history influences job type or job changes among nurses is unknown. We investigated this issue in a large cohort of nurses. Methods The Nurses’ Health Study II is a prospective study of US female nurses enrolled in 1989 (ages 24–44 years). Job status and asthma were assessed in biennial (1989–2011) and asthma-specific questionnaires (1998, 2003). Associations between asthma history at baseline (diagnosis before 1989, n=5311) and job type at baseline were evaluated by multinomial logistic regression. The relations of asthma history and severity during follow-up to subsequent job changes were evaluated by Cox models. Results The analytic cohort included 98 048 nurses. Compared with nurses in education/administration (likely low disinfectant exposure jobs), women with asthma history at baseline were less often employed in jobs with likely high disinfectant exposure, such as operating rooms (odds ratio 0.73 (95% CI 0.63 to 0.86)) and emergency room/inpatient units (0.89 (0.82 to 0.97)). During a 22-year follow-up, nurses with a baseline history of asthma were more likely to move to jobs with lower exposure to disinfectants (HR 1.13 (1.07 to 1.18)), especially among those with more severe asthma (HR for mild persistent: 1.13; moderate persistent 1.26; severe persistent: 1.50, compared with intermittent asthma, p trend: 0.004). Conclusions Asthma history was associated with baseline job type and subsequent job changes among nurses. This may partly reflect avoidance of tasks involving disinfectant use, and may introduce bias in cross-sectional studies on disinfectant exposure and asthma in nurses.