Impact of comorbidities and treatment burden on general well-being among women's cancer survivors.

BACKGROUND: Gains in cancer detection and treatment have meant that more patients are now living with both cancer and other chronic health conditions, which may become burdensome. We used the Patient Experience with Treatment and Self-Management (PETS) framework to study challenges in self-management and its impact on health among survivors of women's cancers who are caring for other chronic health conditions. METHODS: Applicability of the PETS domains among survivors of women's cancers with comorbidities was assessed in focus groups to create the study survey. Women surviving primary breast, cervical, ovarian, or endometrial/uterine cancer treated between 6 months and 3 years prior at two large healthcare systems in Virginia were mailed study invitation letters to complete a telephone-based survey. The survey included questions on cancer treatment history, comorbid conditions prior to cancer, treatment and self-management experiences, health literacy, financial security, and items on self-management activities, self-management difficulties and self-management impact (i.e., role/social activity limitations and physical/mental exhaustion). Additionally, general health was assessed with items from the Patient-Reported Outcomes Measurement Information System (PROMIS). Hierarchical regression models and path analysis were used to examine correlates of self-management impact on general physical health (GPH) and mental health (GMH). RESULTS: Of 1448 patients contacted by mail, 274 (26%) returned an interest form providing their consent to be contacted. Of these, 183 completed the survey. Reasons for non-completion included ineligibility (42), unable to be reached (33) and refusal (6). The majority were survivors of breast (58%) or endometrial/uterine cancer (28%), and 45% resided in non-urban locations. After adjusting for age, race, and cancer type, survivors with higher self-management difficulty reported higher self-management impact, which was associated with lower perceived general health. Reports of higher self-management impact was associated with being single or unmarried, white race, fulltime employed, higher financial insecurity, lower health literacy and more comorbidities. In path analysis, self-management impact was a significant mediator in the association of comorbidity and financial insecurity on GPH and GMH. CONCLUSIONS: Among survivors of women's cancer, pre-diagnosis comorbidity, health literacy, and financial security are associated with psychosocial impact of self-management and general physical and mental health in the 6 month to 3-year period after cancer treatment has ended. The impact of self-management on psychosocial functioning is an important factor among cancer survivors caring for multiple chronic health conditions. This study provides evidence on the importance of assessing cancer survivors' self-management difficulties such as in future interventions to promote health and wellness.

A vaccine based on recombinant modified Vaccinia Ankara containing the nucleoprotein from Lassa virus protects against disease progression in a guinea pig model.

Lassa fever remains the most imported viral haemorrhagic fever in Europe and is responsible for 5000 deaths per year throughout Western Africa. There is no vaccine and treatment is often ineffective. We have developed a vaccine based on modified Vaccinia Ankara expressing the nucleoprotein from Lassa virus (MVALassaNP). This study investigated the immunogenicity (in mice) and efficacy (in guinea pigs) of the MVALassaNP vaccine as a prime/boost or single vaccination regime. ELISA and ELISpot assays confirmed humoral and T-cell immunity following both a prime and prime/boost vaccination, with the prime/boost regime producing a statistically increased response compared to a prime only vaccine (P < 0.0001). The vaccine offered protection in guinea pigs against disease manifestations after challenge with virulent Lassa virus. Clinical signs, weight loss and temperature increases were observed in all animals receiving a control MVA vaccine, after challenge with Lassa virus. In contrast, no clinical signs, fever or weight loss were observed in any of the MVALassaNP vaccinated animals demonstrating that both a single immunisation, and prime/boost regime confer protection against disease progression. In conclusion, the MVALassaNP vaccine candidate elicits an immune response, demonstrates efficacy against Lassa virus disease and is suitable for further preclinical and clinical development.

Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer.

Human deep space and planetary travel is limited by uncertainties regarding the health risks associated with exposure to galactic cosmic radiation (GCR), and in particular the high linear energy transfer (LET), heavy ion component. Here we assessed the impact of two high-LET ions 56Fe and 28Si, and low-LET X rays on genome-wide methylation patterns in human bronchial epithelial cells. We found that all three radiation types induced rapid and stable changes in DNA methylation but at distinct subsets of CpG sites affecting different chromatin compartments. The 56Fe ions induced mostly hypermethylation, and primarily affected sites in open chromatin regions including enhancers, promoters and the edges ("shores") of CpG islands. The 28Si ion-exposure had mixed effects, inducing both hyper and hypomethylation and affecting sites in more repressed heterochromatic environments, whereas X rays induced mostly hypomethylation, primarily at sites in gene bodies and intergenic regions. Significantly, the methylation status of 56Fe ion sensitive sites, but not those affected by X ray or 28Si ions, discriminated tumor from normal tissue for human lung adenocarcinomas and squamous cell carcinomas. Thus, high-LET radiation exposure leaves a lasting imprint on the epigenome, and affects sites relevant to human lung cancer. These methylation signatures may prove useful in monitoring the cumulative biological impact and associated cancer risks encountered by astronauts in deep space.

Weight-of-evidence evaluation of associations between particulate matter exposure and biomarkers of lung cancer.

Research suggests that exposure to ambient particulate matter (PM) may be associated with lung cancer; however, no mode of action (MoA) for this has been established. We applied a weight-of-evidence (WoE) approach to evaluate recent evidence from four realms of research (controlled human exposure, epidemiology, animal, and in vitro) to determine whether the overall evidence supports one or more MoAs by which PM could cause lung cancer. We evaluated three general MoAs: DNA damage and repair; other genotoxic effects, including mutagenicity and clastogenicity; and gene expression, protein expression, and DNA methylation. After assessing individual study quality, we evaluated the strength of the evidence within as well as across disciplines using a modified set of Bradford Hill considerations. We conclude that the overall WoE indicates it is plausible that PM of various size fractions may cause direct DNA damage, but the evidence is insufficient regarding the alternative MoAs we evaluated. More research is needed to determine whether DNA damage can lead to downstream events and, ultimately, lung cancer.

A survey of management practices on Irish dairy farms with emphasis on risk factors for Johne's disease transmission.

BACKGROUND: Johne's disease (JD) is a chronic granulomatous enteritis affecting ruminants. A number of farm management practices are associated with increased risk of JD transmission. The aim of the current study was to document JD-related management practices currently employed on Irish dairy farms. Survey questions focused on calving area (CA), calf and manure management. Independent variables (region, calving-season, enterprise type, herd size and biosecurity status) were used to examine influences on JD associated dependent variables (survey questions). Additionally general biosecurity practices were also examined. RESULTS: Results showed management practices implemented by Irish dairy farmers pose a high risk of JD transmission. Of the farmers surveyed, 97% used the CA for more than one calving, 73.5% and 87.8% pooled colostrum and milk respectively, 33.7% never cleaned the CA between calving's, and 56.6% used the CA for isolating sick cows. Survey results also highlighted that larger herds were more likely to engage in high risk practices for JD transmission, such as pooling colostrum (OR 4.8) and overcrowding the CA (OR 7.8). Larger herds were also less likely than smaller herds to clean the CA (OR 0.28), a practice also considered of risk in the transmission of JD. CONCLUSION: Many management practices associated with risk of JD transmission were commonly applied on Irish dairy farms. Larger herds were more likely to engage in high risk practices for JD transmission. Control programmes should incorporate educational tools outlining the pathogenesis and transmission of JD to highlight the risks associated with implementing certain management practices with regard to JD transmission.

Assessing influence of experimental parameters on formation of PCDD/F from ash derived from fires of CCA-treated wood.

Ash residues from fires of radiata pine timber, both untreated and treated with chromated copper arsenate (CCA), were analyzed for the presence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F). Fire conditions were simulated using a cone calorimeter. The sensitivity of the magnitude and profile of PCDD/F in the ash under controlled experimental conditions were examined to gain an insight into the formation of PCDD/F in a system containing CCA. The total amount of PCDD/F increased from 2.0 ng/kg of ash (0.05 ng of TE/kg of ash, using WHO-TEF) for untreated radiata pine to a maximum of 2700 ng/kg of ash (78 ng of TE/kg of ash) for 0.94% CCA. Ash containing CCA showed a distinct preference for formation of PCDFs, particularly the tetrachloro homologue. It is concluded that PCDD/F formation predominantly occurred via de novo synthesis during smoldering of the char rather than during the initial flaming and pyrolysis. Furthermore, the composition of the CCA constituents present in the timber was controlled to assess whether the physical presence of Cu, a known catalyst in PCDD/F production, was sufficient to account for the formation of PCDD/F in fires of timber impregnated with CCA.

Increased PCDD/F formation in the bottom ash from fires of CCA-treated wood.

Bottom ash that was the result of the combustion of chromated copper arsenate (CCA) treated wood under controlled fire conditions showed an increase of several orders of magnitude in the levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), compared to that of untreated timber. Wood that has been pressure treated with CCA contains copper (II), which is known to catalyse the so-called de novo formation of PCDD/Fs. Comparable levels of PCDD/Fs would be expected in residual ash from burning CCA-treated wood in backyard fires, stoves and wood heaters, as a consequence of similar combustion conditions.

Making mistakes in practice. Developing a consensus statement.

OBJECTIVE: To develop a reference statement for the appropriate management of mistakes in the general practice training environment. METHOD: The setting was a series of focus groups held during workshops with The Royal Australian College of General Practitioners Training Program in the Northern Territory (NT). The participants included NT supervisors and registrars, and representatives of the Consumer Reference Group, Top End Division of General Practice. RESULTS: A reference statement and mutually agreed list of duties for registrars, their supervisors and patients. CONCLUSION: Mistakes are a part of the practice of medicine and can impact on everyone. An appropriate response and the opportunity to reflect and learn from the experience are important elements in minimising the adverse impact. We recommend that the issue of mistakes be considered a priority in the teaching of medicine.

The JIM interview. Edward M. Kennedy, United States Senator.

Senator Edward M. Kennedy has represented Massachusetts in the United States Senate for thirty-six years. He was first elected in 1962 to finish the term of his brother, President John F. Kennedy. Since then, he has been elected to six full terms, and he is now the third most senior member of the senate. The efforts to bring quality health care to every American is a battle that Kennedy has been waging ever since he arrived in the Senate. Recent achievements include the Health Insurance Portability and Accountability Act of 1996, which makes it easier for those who change their job or lose their job to keep their health insurance, and the Children's Health Insurance Act of 1997, which makes health insurance more widely available to children through age 18 in all 50 states. A strong supporter of clinical research, Senator Kennedy cosponsored the Clinical Research Enhancement Act and has been a vocal advocate of stem cell research. He is currently the senior Democrat on the Labor and Human Resources committee in the Senate.

Home care and the ADA: do limitations on coverage violate the law?

To avoid liability, home care agencies must have a firm grasp of the basic requirements of the Americans with Disabilities Act (ADA) and Section 504 of the Rehabilitation Act of 1973 ("Section 504"). Agency leaders must understand the legal issues that arise whenever care is limited or denied to persons with disabilities.

Transpalatal approach for the extracranial surgical repair of transsphenoidal cephaloceles in children.

The surgical treatment of transsphenoidal cephaloceles in children is controversial. Reduction and repair via a transcranial approach are associated with high postoperative rates of morbidity, mortality, and hypothalamic dysfunction. In this study, four patients, aged 3 to 35 months at surgery, underwent successful transpalatal repair of two encephaloceles and two meningoceles. Two patients presented with nasal obstruction in infancy, one presented with unexplained meningitis, and in one patient the lesion was found incidentally during evaluation for seizures. Two children had median cleft face syndrome, another had an associated Arnold-Chiari type I malformation, and the fourth had no other cranial abnormalities. All patients underwent preoperative evaluation including magnetic resonance (MR) imaging. Auditory, ophthalmological, genetic, endocrinological, or other evaluation was undertaken as indicated. Lesions were approached through the median raphe of the hard and soft palates. All cephaloceles were easily visualized and dissected after division of the nasal palatal mucosa. The dural sac and its contents were reduced by surface coagulation after division and dissection of the overlying mucosa. Once reduced, the bone defect was obliterated in three of four patients. The dura was not opened and anomalous neural elements were not resected. At follow-up evaluation, all patients demonstrated resolution of preoperative symptoms without evidence of infection or lasting morbidity. Follow-up MR imaging showed reduction in all cases. The authors conclude that this transpalatal approach is safe and reliable for the treatment of transsphenoidal cephaloceles in young children.

Absence of maladaptive neuronal plasticity after genitofemoral-ilioinguinal neurectomy.

BACKGROUND: Pain (neuralgia) and paresthesia in the inguinal region after lower abdominal surgery is rare. Historically, treatment consisted of neurolysis, local injections, and administration of various medications. The management of chronic pain syndromes is often coordinated by anesthesiologists. Neurolytic therapy is seldom recommended, on the basis of the theory of maladaptive neuronal plasticity. METHODS: Twenty-three patients underwent genitofemoral neurectomy at our institution between 1981 and 1990. Records were reviewed to determine preoperative symptoms, evaluation, and treatment. Patients were contacted and questioned about current symptoms and disability. RESULTS: All records were reviewed. Sixteen (70%) of the patients were located for long-term follow-up. Patients were symptomatic for an average of 3.3 years and underwent 3.1 operations before referral. Inguinal herniorrhaphy was the most common initial surgery (14 of 16 patients). All patients underwent multidisciplinary evaluation. Fifteen underwent L1-2 paraspinous nerve block, and 13 had total pain relief. Postoperative follow-up ranged from 36 to 144 months. Ten patients reported significant pain relief, and three patients reported slight improvement. Three of the six patients who had persistent neuralgia had significant orchialgia. None of the patients who had significant relief had preoperative testicular pain. CONCLUSIONS: Genitofemoral neurectomy provided long-term relief in 62.5% of patients with genitofemoral neuralgia. Severe testicular pain indicated a less favorable outcome. These data do not support the maladaptive neuronal plasticity theory but do support early referral of some patients for neurectomy.

Finding a lasting cure for U.S. health care.

In "Making Competition in Health Care Work" (July-August 1994), Elizabeth Olmsted Teisberg, Michael E. Porter, and Gregory B. Brown ask a question that has been absent from the national debate on health care reform: How can the United States achieve sustained cost reductions while at the same time maintaining quality of care? The authors argue that innovation driven by rigorous competition is the key to successful reform. A lasting cure for health care in the United States should include four basic elements: corrected incentives to spur productive competition, universal insurance to secure economic efficiency, relevant information to ensure meaningful choice, and innovation to guarantee dynamic improvement. In this issue's Perspectives section, eleven experts examine the current state of the health care system and offer their views on the shape that reform should take. Some excerpts: "On the road to innovation, let us not forget to develop the tools that allow physicians, payers, and patients to make better decisions." I. Steven Udvarhelyi; "Health care is not a product or service that can be standardized, packaged, marketed, or adequately judged by consumers according to quality and price." Arnold S. Relman; "Just as antitrust laws are the wise restraints that make competition free in other sectors of the economy, so the right kind of managed competition can work well in health care." Edward M. Kennedy "Biomedical research should be considered primarily an investment in the national economic well-being with additional humanitarian benefits." Elizabeth Marincola.