Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis: the EASI-SWITCH RCT.

Background: Neutropenic sepsis is a common complication of systemic anticancer treatment. There is variation in practice in timing of switch to oral antibiotics after commencement of empirical intravenous antibiotic therapy. Objectives: To establish the clinical and cost effectiveness of early switch to oral antibiotics in patients with neutropenic sepsis at low risk of infective complications. Design: A randomised, multicentre, open-label, allocation concealed, non-inferiority trial to establish the clinical and cost effectiveness of early oral switch in comparison to standard care. Setting: Nineteen UK oncology centres. Participants: Patients aged 16 years and over receiving systemic anticancer therapy with fever (≥ 38°C), or symptoms and signs of sepsis, and neutropenia (≤ 1.0 × 109/l) within 24 hours of randomisation, with a Multinational Association for Supportive Care in Cancer score of ≥ 21 and receiving intravenous piperacillin/tazobactam or meropenem for < 24 hours were eligible. Patients with acute leukaemia or stem cell transplant were excluded. Intervention: Early switch to oral ciprofloxacin (750 mg twice daily) and co-amoxiclav (625 mg three times daily) within 12-24 hours of starting intravenous antibiotics to complete 5 days treatment in total. Control was standard care, that is, continuation of intravenous antibiotics for at least 48 hours with ongoing treatment at physician discretion. Main outcome measures: Treatment failure, a composite measure assessed at day 14 based on the following criteria: fever persistence or recurrence within 72 hours of starting intravenous antibiotics; escalation from protocolised antibiotics; critical care support or death. Results: The study was closed early due to under-recruitment with 129 patients recruited; hence, a definitive conclusion regarding non-inferiority cannot be made. Sixty-five patients were randomised to the early switch arm and 64 to the standard care arm with subsequent intention-to-treat and per-protocol analyses including 125 (intervention n = 61 and control n = 64) and 113 (intervention n = 53 and control n = 60) patients, respectively. In the intention-to-treat population the treatment failure rates were 14.1% in the control group and 24.6% in the intervention group, difference = 10.5% (95% confidence interval 0.11 to 0.22). In the per-protocol population the treatment failure rates were 13.3% and 17.7% in control and intervention groups, respectively; difference = 3.7% (95% confidence interval 0.04 to 0.148). Treatment failure predominantly consisted of persistence or recurrence of fever and/or physician-directed escalation from protocolised antibiotics with no critical care admissions or deaths. The median length of stay was shorter in the intervention group and adverse events reported were similar in both groups. Patients, particularly those with care-giving responsibilities, expressed a preference for early switch. However, differences in health-related quality of life and health resource use were small and not statistically significant. Conclusions: Non-inferiority for early oral switch could not be proven due to trial under-recruitment. The findings suggest this may be an acceptable treatment strategy for some patients who can adhere to such a treatment regimen and would prefer a potentially reduced duration of hospitalisation while accepting increased risk of treatment failure resulting in re-admission. Further research should explore tools for patient stratification for low-risk de-escalation or ambulatory pathways including use of biomarkers and/or point-of-care rapid microbiological testing as an adjunct to clinical decision-making tools. This could include application to shorter-duration antimicrobial therapy in line with other antimicrobial stewardship studies. Trial registration: This trial is registered as ISRCTN84288963. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/140/05) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Neutropenic sepsis, or infection with a low white blood cell count, can occur following cancer treatment. Usually patients receive treatment with intravenous antibiotics (antibiotics delivered into a vein) for two or more days. Patients at low risk of complications from their infection may be able to have a shorter period of intravenous antibiotics benefitting both patients and the NHS. The trial compared whether changing from intravenous to oral antibiotics (antibiotics taken by mouth as tablets or liquid) 12­24 hours after starting antibiotic treatment ('early switch') is as effective as usual care. Patients could take part if they had started intravenous antibiotics for low-risk neutropenic sepsis. Patients were randomly allocated to 'early switch' or to usual care. The main outcome measured was treatment failure. Treatment failure happened if fever persisted or recurred despite antibiotics, if patients needed to change antibiotics, if they needed to be re-admitted to hospital or needed to be admitted to intensive care within 14 days or died. We had originally intended that 628 patients would take part, but after review of the design of the study the number needed to take part was revised to 230. We were not able to complete the trial as planned as unfortunately only 129 patients took part. As the trial was smaller than expected we were not able to draw conclusions as to whether 'early switch' is no less effective than usual care. Our findings suggest that 'early switch' might result in a shorter time in hospital initially; however, treatment failure was more likely to occur, meaning some patients had to return to hospital for further antibiotics. There were no differences in side effects and no serious complications from treatment or treatment failure (such as intensive care admission or death) among the 65 patients in the 'early switch' group. Patients were satisfied with 'early switch'. Early switch may be a treatment option for some patients with low-risk neutropenic sepsis who would prefer a shorter duration of hospital admission but accept a risk of needing hospital re-admission.

Do clinical trials change practice? A longitudinal, international assessment of colorectal cancer prescribing practices.

INTRODUCTION: Over half of the 1.5 million individuals globally who are diagnosed with colorectal cancer (CRC) present with stage II-III disease. Understanding clinician attitudes towards treatment for this group is paramount to contextualise real-world outcomes and plan future trials. The aim of this study was to assess clinician awareness of trials assessing the optimal duration of CRC adjuvant therapy, their attitudes towards shorter treatment and their self-reported practice. METHODS: A survey was developed using OnlineSurveys® and distributed to clinicians in April 2019, with a follow-up survey disseminated to a subset of respondents in August 2020. Microsoft Excel® and Stata® were used for analysis. RESULTS: 265 clinicians replied to the first survey, with the majority aware of findings from the International Duration Evaluation of Adjuvant Therapy collaboration and contributory trials. Practice change was greatest for patients under 70 with low-risk stage III CRC, with most uncertainty around using 3-months of doublet chemotherapy for high-risk stage II disease. In August 2020, clinicians (n = 106) were more likely to use 3-months of FOLFOX for low-risk stage III disease and 3-months of CAPOX for stage II disease compared to April 2019. There was no indication that the COVID-19 pandemic had enduring changes on treatment decisions beyond those made in response to trial evidence. DISCUSSION: Clinicians use a risk-stratified approach to treat CRC the adjuvant setting. Lower utilisation of doublet chemotherapy for older and stage II patients has affected the extent of trial implementation. Active dialogue regarding how trial results apply to these groups may improve consensus.

Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis (the EASI-SWITCH trial): study protocol for a randomised controlled trial.

BACKGROUND: Neutropenic sepsis remains a common treatment complication for patients receiving systemic anti-cancer treatment. The UK National Institute for Health and Care Excellence have not recommended switching from empirical intravenous antibiotics to oral antibiotics within 48 h for patients assessed as low risk for septic complications because of uncertainty about whether this would achieve comparable outcomes to using intravenous antibiotics for longer. The UK National Institute for Health Research funded the EASI-SWITCH trial to tackle this uncertainty. METHODS: The trial is a pragmatic, randomised, non-inferiority trial that aims to establish the clinical and cost-effectiveness of early switching from intravenous to oral antibiotics in cancer patients with low-risk neutropenic sepsis. Patients ≥ 16 years, receiving systemic anti-cancer treatment (acute leukaemics/stem cell transplants excluded), with a temperature of > 38 °C, neutrophil count ≤ 1.0 × 109/L, MASCC (Multinational Association of Supportive Care in Cancer) score ≥ 21 and receiving IV piperacillin/tazobactam or meropenem for less than 24 h are eligible to participate. Patients are randomised 1:1 either (i) to switch to oral ciprofloxacin and co-amoxiclav within 12-24 h of commencing intravenous antibiotics, completing at least 5 days total antibiotics (intervention), or (ii) to continue intravenous antibiotics for at least 48 h, with ongoing antibiotics being continued at the physician's discretion (control). Patients are discharged home when their physician deems it appropriate. The primary outcome measure is a composite of treatment failures as assessed at day 14. The criteria for treatment failure include fever persistence or recurrence 72 h after starting intravenous antibiotics, escalation from protocolised antibiotics, hospital readmission related to infection/antibiotics, critical care support or death. Based on a 15% treatment failure rate in the control group and a 15% non-inferiority margin, the recruitment target is 230 patients. DISCUSSION: If the trial demonstrates non-inferiority of early switching to oral antibiotics, with potential benefits for patient quality of life and resource savings, this finding will have significant implications for the routine clinical management of those with low-risk neutropenic sepsis. TRIAL REGISTRATION: ISRCTN: 84288963. Registered on the 1 July 2015. https://doi.org/10.1186/ISRCTN84288963. EudraCT: 2015-002830-35.

Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial.

BACKGROUND: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer. METHODS: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment. FINDINGS: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants). INTERPRETATION: Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes. FUNDING: Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.

Genome sequence of the basal haplorrhine primate Tarsius syrichta reveals unusual insertions.

Tarsiers are phylogenetically located between the most basal strepsirrhines and the most derived anthropoid primates. While they share morphological features with both groups, they also possess uncommon primate characteristics, rendering their evolutionary history somewhat obscure. To investigate the molecular basis of such attributes, we present here a new genome assembly of the Philippine tarsier (Tarsius syrichta), and provide extended analyses of the genome and detailed history of transposable element insertion events. We describe the silencing of Alu monomers on the lineage leading to anthropoids, and recognize an unexpected abundance of long terminal repeat-derived and LINE1-mobilized transposed elements (Tarsius interspersed elements; TINEs). For the first time in mammals, we identify a complete mitochondrial genome insertion within the nuclear genome, then reveal tarsier-specific, positive gene selection and posit population size changes over time. The genomic resources and analyses presented here will aid efforts to more fully understand the ancient characteristics of primate genomes.

Cost-Effective Recruitment Strategies That Attract Underrepresented Minority Undergraduates Who Persist to STEM Doctorates.

The paucity of underrepresented minorities (URMs) earning science, technology, engineering, and mathematics (STEM) degrees remains an issue in revitalizing the U.S. biomedical workforce. Due to reductions in federal funding, maintaining the integrity of programs that focus on URM retention and recruitment is crucial. We present data on the mechanisms used to recruit URM students to our program (e.g., email, events, referrals, website), which individually were equally effective in attracting applicants to the program. Recruitment mechanisms were grouped and further classified relative to their cost to implement as lower and higher cost. Our results indicate that lower cost mechanisms, statistically, were as effective as higher cost mechanisms in recruiting students who persisted to PhD programs. Using a binary logistic regression model to predict PhD matriculation, higher cost mechanisms were not significant predictors of PhD matriculation. Collectively, these data demonstrate for the first time that lower cost mechanisms can be as successful in recruiting URM students to summer programs who pursue PhDs in STEM fields.

The PAndemic INfluenza Triage in the Emergency Department (PAINTED) pilot cohort study.

BACKGROUND: Research needs to be undertaken rapidly in the event of an influenza pandemic to develop and evaluate triage methods for people presenting to the emergency department with suspected pandemic influenza. OBJECTIVES: We aimed to pilot a research study to be undertaken in a pandemic to identify the most accurate triage method for patients presenting to the emergency department with suspected pandemic influenza. The objectives of the pilot study were to develop a standardised clinical assessment form and secure online database; test both using data from patients with seasonal influenza; seek clinician views on the usability of the form; and obtain all regulatory approvals required for the main study. DESIGN: Study methods were piloted using an observational cohort study and clinician views were sought using qualitative, semistructured interviews. SETTING: Six acute hospital emergency departments. PARTICIPANTS: Patients attending the emergency department with suspected seasonal influenza during winter 2012-13 and clinicians working in the emergency departments. MAIN OUTCOME MEASURES: Adverse events up to 30 days were identified, but analysis of the pilot data was limited to descriptive reporting of patient flow, data completeness and patient characteristics. RESULTS: Some 165 patients were identified, of whom 10 withdrew their data, leaving 155 (94%) for analysis. Follow-up data were available for 129 of 155 (83%), with 50 of 129 (39%) being admitted to hospital. Three cases (2%) were recorded as having suffered an adverse outcome. There appeared to be variation between the hospitals, allowing for small numbers. Three of the hospitals identified 150 of 165 (91%) of the patients, and all 10 withdrawing patients were at the same hospital. The proportion with missing follow-up data varied from 8% to 31%, and the proportion admitted varied from 4% to 85% across the three hospitals with meaningful numbers of cases. All of the deaths were at one hospital. There was less variation between hospitals in rates of missing data, and for most key variables missing rates were between 5% and 30%. Higher missing rates were recorded for blood pressure (39%), inspired oxygen (43%), capillary refill (36%) and Glasgow Coma Scale score (43%). Chest radiography was performed in 51 of 118 cases, and electrocardiography in 40 of 111 cases with details recorded. Blood test results were available for 32 of 155 cases. The qualitative interviews revealed generally positive views towards the standardised assessment form. Concerns about lack of space for free text were raised but counterbalanced by appreciation that it fitted on to one A4 page. A number of amendments were suggested but only three of these were suggested by more than one participant, and no suggestions were made by more than two participants. CONCLUSIONS: A standardised assessment form is acceptable to clinicians and could be used to collect research data in an influenza pandemic, but analysis may be limited by missing data. FUTURE WORK: An observational cohort study to identify the most accurate triage method for predicting severe illness in emergency department attendees with suspected pandemic influenza is set up and ready to activate if, or when, a pandemic occurs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56149622. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 3. See the NIHR Journals Library website for further project information.

Audition assessment using the NIH Toolbox.

The NIH Toolbox project has assembled measurement tools to assess a wide range of human perception and ability across the lifespan. As part of this initiative, a small but comprehensive battery of auditory tests has been assembled. The main tool of this battery, pure-tone thresholds, measures the ability of people to hear at specific frequencies. Pure-tone thresholds have long been considered the "gold standard" of auditory testing, and are normally obtained in a clinical setting by highly trained audiologists. For the purposes of the Toolbox project, an automated procedure (NIH Toolbox Threshold Hearing Test) was developed that allows nonspecialists to administer the test reliably. Three supplemental auditory tests are also included in the Toolbox auditory test battery: assessment of middle-ear function (tympanometry), speech perception in noise (the NIH Toolbox Words-in-Noise Test), and self-assessment of hearing impairment (the NIH Toolbox Hearing Handicap Inventory Ages 18-64 and the NIH Toolbox Hearing Handicap Inventory Ages 64+). Tympanometry can help differentiate conductive from sensorineural pathology. The NIH Toolbox Words-in-Noise Test measures a listener's ability to perceive words in noisy situations. This ability is not necessarily predicted by a person's pure-tone thresholds; some people with normal hearing have difficulty extracting meaning from speech sounds heard in a noisy context. The NIH Toolbox Hearing Handicap Inventory focuses on how a person's perceived hearing status affects daily life. The test was constructed to include emotional and social/situational subscales, with specific questions about how hearing impairment may affect one's emotional state or limit participation in specific activities. The 4 auditory tests included in the Toolbox auditory test battery cover a range of auditory abilities and provide a snapshot of a participant's auditory capacity.

The past and present of and potential for the domestic (water) buffalo in Africa.

Egypt is the only country in Africa where domestic buffalo have a long-term presence and constitute an important part of the array of domestic animal resources. Attempts to introduce buffalo to other African countries have been made since at least the 1920s. Nine such attempted introductions are documented in this paper, although for most cases, there is very limited information. Buffalo have disappeared without trace in some countries and were slaughtered in at least two because of lack of adaptation or susceptibility to disease. In addition to Egypt, only Tanzania and Mozambique are known to have buffalo in 2012. There are suitable ecological niches for buffalo in many African countries. Failure to provide sufficient financial resources by governments, initially small numbers of animals and probable lack of interest by the private sector are among the reasons for the failure of buffalo to become a contributor to African livestock production. Policy makers and development agencies should very carefully consider the overall benefits against the overall costs of attempted introductions of buffalo (and of other exotic livestock species) in to African countries.

Mortality and cost of pneumonia after stroke for different risk groups.

An evidenced-based approach to detecting and treating dysphagia needs to be informed by the costs and risks associated with pneumonia. In this study, the cost of pneumonia during hospitalization after stroke and the effect of pneumonia on mortality were estimated. The effect of pneumonia on mortality and costs for different levels of risk were analyzed as well. The data come from the 2005 and 2006 Nationwide Inpatient Sample. Regression models, including the propensity for pneumonia, were used to estimate the in-hospital mortality-associated pneumonia, as well as the marginal cost of pneumonia on the hospitalization. A stratified analysis based on quintile of propensity for pneumonia was also undertaken. There were 183,976 hospitalizations for stroke in the sample. The adjusted relative risk of death associated with pneumonia was 2.0 (95% confidence interval [CI], 1.9-2.1). The average marginal cost of pneumonia on the hospitalization was $27,633 (95% CI, $27,078-$27,988). The quintile of hospitalizations with the highest propensity for pneumonia had the highest average marginal cost associated with pneumonia and the lowest adjusted relative risk of death. There was an inverse relationship between adjusted relative risk of death and propensity for pneumonia. The data indicate that pneumonia after stroke is associated with higher mortality and hospitalization costs. Patients with the lowest risk for pneumonia have the highest risk for death associated with pneumonia. Screening is important at all levels of risk.

A cost-effectiveness analysis of screening methods for dysphagia after stroke.

OBJECTIVE: To provide a cost-effectiveness analysis of dysphagia screening in the acute poststroke period with use of a videofluoroscopic swallowing study, a clinical bedside swallowing evaluation, or a combined approach. DESIGN: Decision-analysis model. METHODS: A decision-analysis model was used with information derived from multiple data sources, including meta-analyses and other relevant clinical studies. Univariate and probabilistic sensitivity analyses were performed. MAIN OUTCOME MEASURES: The analysis assessed direct medical costs of pneumonia. Strategies were compared on the basis of an incremental cost-effectiveness analysis, with effectiveness measured in quality-adjusted life-years. RESULTS: The strategy of having each patient undergo a videofluoroscopic swallowing study for dysphagia was more effective and less costly than the strategies of clinical bedside swallowing evaluation alone or a combined approach. The model was most influenced by the reduction in the risk of pneumonia attributable to the treatment of mild/moderate and severe dysphagia, the effectiveness of treatment with clinical bedside swallowing evaluation, the baseline probability of pneumonia, and the cost of a videofluoroscopic swallowing study. CONCLUSIONS: A videofluoroscopic swallowing study is cost-effective and often saves costs compared with a clinical bedside swallowing evaluation alone or a combined approach. Research aimed at improving the understanding of the effectiveness of treatment for dysphagia in the prevention of aspiration pneumonia and resulting mortality would improve the model.

A vertebrate case study of the quality of assemblies derived from next-generation sequences.

The unparalleled efficiency of next-generation sequencing (NGS) has prompted widespread adoption, but significant problems remain in the use of NGS data for whole genome assembly. We explore the advantages and disadvantages of chicken genome assemblies generated using a variety of sequencing and assembly methodologies. NGS assemblies are equivalent in some ways to a Sanger-based assembly yet deficient in others. Nonetheless, these assemblies are sufficient for the identification of the majority of genes and can reveal novel sequences when compared to existing assembly references.

Accuracy of angular measurements and assessment of distortion in the mandibular third molar region on panoramic radiographs.

OBJECTIVE: The objective of this study was to examine distortion on panoramic radiographs by assessing the accuracy of angular measurements in the mandibular third molar region on panoramic radiographs using computed tomography (CT). METHODS: Images from patients referred to a radiology practice for low-dose CT scans of their lower third molars were used in this study. The angle between the long axes of the second and third molars was assessed on panoramic radiographs and the corresponding CT images. Apparent tilting of the tooth across the arch on the panoramic image and the bucco-lingual inclination on CT were also recorded and compared. RESULTS: Eighty-eight patients had 163 mandibular third molars. The mean difference between the panoramic measurements and the CT measurements was -1.44 degrees, indicating that on the panoramic radiograph the third molar appeared less mesially inclined on average. This pattern was present in most cases, but in 64 cases the third molar appeared more mesially inclined on the panoramic radiograph. It was not possible to predict the direction of the discrepancy based on the radiographic findings. The discrepancy between the 2 measurements was greater if the third molar appeared tilted across the arch on the panoramic image, and tilted teeth showed a higher bucco-lingual inclination on reformatted CT images. CONCLUSIONS: Distortions inherent in panoramic imaging because of projection geometry produce discrepancies in the angular measurements in the mandibular third molar regions on panoramic radiographs. Interpretation of third molar angulation from panoramic radiographs is often unreliable and may not accurately reflect the true orientation of the tooth. Apparent tilting of the tooth across the arch on the panoramic radiograph exacerbates the problem and appears to correlate with the bucco-lingual inclination of the third molar as visualized on reformatted CT images.

Attitudes towards weight and weight assessment in oncology patients: survey of hospice staff and patients with advanced cancer.

The objective of this study was to compare attitudes of hospice staff towards weight loss and weight assessment in the hospice setting with those of patients with advanced malignancy in the hospital outpatient setting. Two paper-based questionnaires (one for staff and one for patients) were designed. The staff survey was circulated to all hospices in the UK and Ireland, and the patient questionnaire was given to patients attending three oncological care clinics in Belfast, Northern Ireland; Wolverhampton, England; and Auckland, New Zealand. The staff survey was posted to the medical director of each of the 215 hospices in the UK and Ireland. A total of 129 oncology outpatients with a confirmed diagnosis of malignancy and no longer receiving curative oncological interventions took part in the questionnaire. The main outcome measure was descriptive information about hospice weighing practices and attitudes of hospice staff towards weighing patients, and descriptive information was collected about patient attitudes to weighing and weight loss. We found that weighing practices vary across hospices in UK and Ireland. Patients attending the majority of hospices, 96/146 (66%), are rarely weighed. A little over half of hospice staff, 81/146 (56%) considered that weighing could cause patients to be upset. However, 124/129 (96%) of patients with advanced cancer reported that they had never found the experience of being weighed in a healthcare facility upsetting. Some 95/129 (74%) of patients weighed themselves at home and 89% would want to know if their weight was changing. While there is reluctance on the part of many hospice staff to weigh patients, most patients with advanced malignancy in the hospital setting do not report weight measurement to be upsetting.

Hospitalizations of adults with spina bifida and congenital spinal cord anomalies.

OBJECTIVE: To examine hospital admission records from a large cohort of persons with spina bifida (SB) with a variety of insurers to provide descriptive detail about adult hospital use for persons with SB and associated disorders in terms of primary diagnosis for hospitalization, age, sex, payer source, lengths of stay, and total charges. DESIGN: Retrospective secondary data analysis from the Nationwide Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project for 2004 and 2005 of hospitalizations for adults with SB or associated spinal cord anomalies. SETTING: Records from U.S. inpatient hospital admissions. PARTICIPANTS: Persons with SB age 18 years and older. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Diagnoses associated with hospitalizations and death. RESULTS: The most common primary diagnosis for hospitalization was urinary tract infection, followed by complications from devices/grafts/implants and skin wounds. Sepsis accounted for the most deaths. Approximately one third of hospitalizations were for primary diagnoses of potentially preventable conditions. Hospitalizations associated with a primary diagnosis of a potentially preventable condition occurred most often in those less than 51 years of age and in rural or urban nonteaching hospitals. CONCLUSIONS: Reducing the number of secondary medical conditions with proactive and preventative approaches to health care could reduce the morbidity, mortality, and cost for health care for this group.

Trends in the rehabilitation therapist workforce in underserved areas: 1980-2000.

CONTEXT: There is little information about how increases in the rehabilitation therapist workforce have been distributed over the nation. There is evidence that rural areas continue to face a shortage of trained rehabilitation providers. There has also been little attention to therapist distribution in non-rural settings where health professionals are in short supply. PURPOSE: To assess the change in the distribution of rehabilitation therapists in 1980, 1990, and 2000 across counties with different levels of health professional shortages and the difference between metropolitan and non-metropolitan counties. METHODS: A trend analysis of cross-sectional data of employment of physical therapists, occupational therapists, and speech-language pathologists from 1980 to 2000 by county, relative to population, was done. The groups were stratified by shortage area, partial shortage area, and non-shortage counties and metropolitan and non-metropolitan counties. FINDINGS: There is a maldistribution of rehabilitation therapists in the United States. Although the absolute differences have remained the same or, in most instances, have increased, the relative change was greatest in the shortage areas and non-metropolitan areas. If the trends in the relative changes continue, the absolute differences may begin to narrow. CONCLUSIONS: This study provides evidence that there are maldistributions of rehabilitation therapists in traditionally underserved areas. It is unclear if these maldistributions represent a shortage of rehabilitation therapists. Continued monitoring of the rehabilitation therapist workforce and the determination of the optimal supply should be undertaken in the future.

Risk assessment due to environmental exposures to fibrous particulates associated with taconite ore.

In the early 1970s, it became a concern that exposure to the mineral fibers associated taconite ore processed in Silver Bay, Minnesota would cause asbestos-related disease including gastrointestinal cancer. At that time data gaps existed which have now been significantly reduced by further research. To further our understanding of the types of airborne fibers in Silver Bay we undertook a geological survey of their source the Peter Mitchell Pit, and found that there are no primary asbestos minerals at a detectable level. However we identified two non-asbestos types of fibrous minerals in very limited geological locales. Air sampling useful for risk assessment was done to determine the type, concentrations and size distribution of the population of airborne fibers around Silver Bay. Approximately 80% of the airborne fibers have elemental compositions consistent with cummingtonite-grunerite and the remaining 20% have elemental compositions in the tremolite-actinolite series. The mean airborne concentration of both fiber types is less than 0.00014 fibers per milliliter that is within the background level reported by the World Health Organization. We calculate the risk of asbestos-related mesothelioma and lung cancer using a variety of different pessimistic assumptions. (i) that all the non-asbestos fibers are as potent as asbestos fibers used in the EPA-IRIS listing for asbestos; with a calculated risk of asbestos-related cancer for environmental exposure at Silver Bay of 1 excess cancer in 28,500 lifetimes (or 35 excess cancers per 1,000,000 lifetimes) and secondly that taconite associated fibers are as potent as chrysotile the least potent form of asbestos. The calculated risk is less than 0.77 excess cancer case in 1,000,000 lifetimes. Finally, we briefly review the epidemiology studies of grunerite asbestos (amosite) focusing on the exposure conditions associated with increased risk of human mesothelioma.

The ACTN3 R577X polymorphism in East and West African athletes.

PURPOSE: To determine the frequency of the ACTN3 R577X polymorphism (functional R allele and nonfunctional X allele) in a variety of African populations and to examine its influence on the success of elite East African endurance runners and West African sprinters. METHODS: The R577X polymorphism was genotyped in 198 Ethiopian controls and 76 elite Ethiopian endurance athletes, 158 Kenyan controls and 284 elite Kenyan endurance runners, and 60 Nigerian controls and 62 elite Nigerian power athletes. Statistical analyses were performed by exact tests of population differentiation, using Arlequin, version 3. Analyses were carried out using 1 x 10(6) Markov chain steps, and 1 x 10(5) dememorization steps. RESULTS: The frequency of the X allele was extremely low among Kenyans and Nigerians (approximately 1% homozygosity) and higher in Ethiopians (approximately 11% homozygosity). The low baseline frequencies of the three populations tested mean that any associations with sprint performance would likely be obscured. In Ethiopians, where baseline levels of 577XX were about 11%, there was no increased frequency in the endurance athletes. CONCLUSION: Our data suggest that alpha-actinin-3 deficiency is not a major influence on performance in African athletes.