Fanconi's anemia treated by allogeneic marrow transplantation

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.     

Perceived Value of Teaching and Learning Curriculum Programs Among Pharmacy Practice Department Chairs

Objective. To determine the perceived value that pharmacy practice department chairs ascribe to pharmacy faculty candidates having completed a teaching and learning curriculum (TLC) program and related activities.Methods. An 18-item survey instrument was created that was intended to capture the overall impressions of pharmacy practice chairs regarding the value of TLC programs, relative importance compared to other accomplishments (eg, residency completion, board certification), and importance of specific activities. Following pilot testing and establishment of intra-rater reliability, invitations to complete the electronic survey instrument were sent to pharmacy practice chairs (or their equivalent) at accredited Doctor of Pharmacy (PharmD) programs in the United States.Results. Of the 127 pharmacy practice chairs invited, 53 completed the survey (response rate of 41.7%). The majority of respondents held a PharmD degree (90.6%), had been in their role of chair for zero to five years (60.4%), and represented a private institution (54.7%). The majority of respondents who answered the question (32 of 49) felt it was very important or important (16.3% and 49.0%, respectively) that teaching experiences be completed within a formal teaching and learning curriculum program. These programs were believed to be most important for candidates with less than five years of professional experience. Teaching and learning curriculum programs were not deemed to be more important than other accomplishments by most responders. The perceived most important TLC program activities were instruction on didactic and experiential teaching strategies, and experience developing learning objectives, developing examination items, evaluating examination results, and facilitating case conferences or practice laboratory activities.Conclusion. Teaching and learning curriculum programs may provide the foundational experiences needed for pharmacy graduates to stand out among other candidates, although department chairs’ perceptions of the value of teaching and learning curriculum experiences varied.     

Embracing complexity and uncertainty to create impact: exploring the processes and transformative potential of co-produced research through development of a social impact model

The potential use, influence and impact of health research is seldom fully realised. This stubborn problem has caused burgeoning global interest in research aiming to address the implementation ‘gap’ and factors inhibiting the uptake of scientific evidence. Scholars and practitioners have questioned the nature of evidence used and required for healthcare, highlighting the complex ways in which knowledge is formed, shared and modified in practice and policy. This has led to rapid expansion, expertise and innovation in the field of knowledge mobilisation and funding for experimentation into the effectiveness of different knowledge mobilisation models. One approach gaining prominence involves stakeholders (e.g. researchers, practitioners, service users, policy-makers, managers and carers) in the co-production, and application, of knowledge for practice, policy and research (frequently termed integrated knowledge translation in Canada). Its popularity stems largely from its potential to address dilemmas inherent in the implementation of knowledge generated using more reductionist methods. However, despite increasing recognition, demands for co-produced research to illustrate its worth are becoming pressing while the means to do so remain challenging. This is due not only to the diversity of approaches to co-production and their application, but also to the ways through which different stakeholders conceptualise, measure, reward and use research. While research co-production can lead to demonstrable benefits such as policy or practice change, it may also have more diffuse and subtle impact on relationships, knowledge sharing, and in engendering culture shifts and research capacity-building. These relatively intangible outcomes are harder to measure and require new emphases and tools. This opinion paper uses six Canadian and United Kingdom case studies to explore the principles and practice of co-production and illustrate how it can influence interactions between research, policy and practice, and benefit diverse stakeholders. In doing so, we identify a continuum of co-production processes. We propose and illustrate the use of a new ‘social model of impact’ and framework to capture multi-layered and potentially transformative impacts of co-produced research. We make recommendations for future directions in research co-production and impact measurement.     

Effect of nitrous acid on lung function in asthmatics: a chamber study.

Nitrous acid, a component of photochemical smog and a common indoor air pollutant, may reach levels of 100 ppb where gas stoves and unvented portable kerosene heaters are used. Nitrous acid is a primary product of combustion and may also be a secondary product by reaction of nitrogen dioxide with water. Because the usual assays for nitrogen dioxide measure several oxides of nitrogen (including nitrous acid) together, previous studies of indoor nitrogen dioxide may have included exposure to and health effects of nitrous acid. To assess the respiratory effects of nitrous acid exposure alone, we carried out a double-blinded crossover chamber exposure study with 11 mildly asthmatic adult subjects. Each underwent 3-hr exposures to 650 ppb nitrous acid and to filtered room air with three 20-min periods of moderate cycle exercise. Symptoms, respiratory parameters during exercise, and spirometry after exercise were measured. A statistically significant decrease in forced vital capacity was seen on days when subjects were exposed to nitrous acid. This effect was most marked at 25 min and 85 min after exposure began. Aggregate respiratory and mucous membrane symptoms were also significantly higher with nitrous acid. We conclude that this concentration and duration of exposure to nitrous acid alters lung mechanics slightly, does not induce significant airflow obstruction, and produces mild irritant symptoms in asthmatics.     

Occupational paraquat exposure of agricultural workers in large Costa Rican farms

Objective  Paraquat is an herbicide widely used worldwide. This study determined the extent of occupational exposure to paraquat among farm workers in Costa Rica and identified determinants of occupational exposure. Methods  Twenty-four hour urine samples were collected from 119 paraquat handlers and 54 non-handlers from banana, coffee and palm oil farms. Information about herbicide handling operations was also collected. The urinary paraquat levels were determined by an enzyme-linked immunosorbent assay (ELISA) with a limit of quantification (LOQ) of 2 ng/mL. Inhalable dust and airborne paraquat levels were simultaneously measured for a subset of the participants. Results  Urinary paraquat measurements were non-detectable or very low when workers did not handle paraquat. For handlers, 83.3, 47.1 and 63.9% of the samples were below the LOQ on before-, during- and after-paraquat spray days, respectively. The arithmetic mean (±SD) of urinary paraquat level on days when workers handled paraquat was 6.3 (±10.45) μg/24 h. Paraquat exposures among handlers on spray day were significantly associated with the type of crop. Conclusion  Non-handlers had negligible urinary paraquat, while detectable paraquat exposures were observed among handlers on spray day. Urinary paraquat levels were different by crop.     

A multivariate cure model for left‐censored and right‐censored data with application to colorectal cancer screening patterns

We develop a multivariate cure survival model to estimate lifetime patterns of colorectal cancer screening. Screening data cover long periods of time, with sparse observations for each person. Some events may occur before the study begins or after the study ends, so the data are both left‐censored and right‐censored, and some individuals are never screened (the ‘cured’ population). We propose a multivariate parametric cure model that can be used with left‐censored and right‐censored data. Our model allows for the estimation of the time to screening as well as the average number of times individuals will be screened. We calculate likelihood functions based on the observations for each subject using a distribution that accounts for within‐subject correlation and estimate parameters using Markov chain Monte Carlo methods. We apply our methods to the estimation of lifetime colorectal cancer screening behavior in the SEER‐Medicare data set. Copyright © 2016 John Wiley & Sons, Ltd.     

Medical evaluation for respirator use

The purpose of a respirator is to prevent the inhalation of harmful airborne substances or to provide a source of respirable air when breathing in oxygen-deficient atmospheres. For a physician to recommend the use of respirator, general background information on respiratory-protective devices is required. The first part of this clinical practice review describes the general aspects of industrial hygiene, respirators and a respirator-certification program. The second part addresses matters related to medical certification for respirator use. Medical certification for respirators is an important part of the activities of the occupational physician. To determine whether a worker is able to tolerate the added strain of a respiratory protective device is a complex process in which factors such as fitness for work, health of the individual, characteristics of the work itself, and the properties, type, and requirements of the respiratory protective device, have to be considered. Medical certification is of utmost importance for respirator use, and it should be viewed as an element in a comprehensive respiratory protection program. A comprehensive program is the key element in affording the workers' effective respiratory protection once the initial steps of the hierarchy of methods of hazard control have proved insufficient or infeasible. As a result, the need for the industrial hygiene/safety officer, the worker, the employer and the medical professional to work as a team is much more than in any other field of occupational medicine--a necessary requirement for making the right decision.     

Comparative Soil Metal Analyses in Sudbury (Ontario,Canada) and Lubumbashi (Katanga,DR-Congo)

DR-Congo is a main world producer of copper (Cu) and cobalt (Co). Several hydrometallurgical plants and smelters also produced zinc, arsenic, and cadmium as by-products. In Sudbury (Canada), the production of nickel, copper and other metals has been maintained at high levels while industrial SO₂ emissions have been reduced by approximately 90% through combination of industrial technological developments and legislated controls. Metal analysis in the present study revealed that the levels of copper and cobalt in soils from mining sites in the Lubumbashi (DR-Congo) were up to 200 fold higher compared to contaminated Sudbury sites and tailings. Zinc content in soil samples from some mining areas in Lubumbashi was at least 70 times higher compared to samples from the Sudbury area. Nickel content in soil samples from Lubumbashi were much lower compared to the Sudbury Region samples. Overall, this study confirms that the African Copper belt region is among the ten most polluted areas in the world.     

An overload hypothesis for pulmonary clearance of UICC amosite fibres inhaled by rats.

Two types of experiments were carried out to examine the effects of deposition and clearance on the accumulation in the lungs of rats of inhaled fibres of UICC amosite. In the first experiment the mass lung burdens of the dust in question were measured as a function of the time at which animals were killed after the cessation of the six week exposure period, and in the second the masses were measured for rats removed from exposure and killed at intervals during the exposure period itself. The experimental conditions were chosen to complement those of earlier work. Taken together with the results of that earlier work, the new results provide the basis for a simple mathematical model of the kinetics of deposition and clearance which appears to account for the major observed trends. Most significantly, there is strong evidence for an overload of clearance at high lung burdens (exceeding about 1500 micrograms/rat), in which a breakdown occurs of the intermediate rate clearance mechanisms (time constants of the order of 12 days). This hypothesis is supported for inhaled asbestos dust, quartz dust, and diesel fume by results obtained elsewhere. Biological explanations for the clearance overload hypothesis are at present speculative, involving discussion of the role of the macrophage in pulmonary clearance. It is believed that the clearance overload hypothesis could have possible consequences for people occupationally exposed to airborne dusts.