Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders

In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.

     

Investigation of the phenylalanine hydroxylase gene and tardive dyskinesia.

Phenylketonuria (PKU), an inborn error of phenylalanine metabolism, has been shown to be a risk factor for tardive dyskinesia (TD). In male psychiatric patients there was a significant relationship between TD and measures of plasma phenylalanine following ingestion of a standardized phenylalanine dose that was indicative of higher brain availability of phenylalanine in patients with TD. In addition, a medical food formulation consisting of branched chain amino acids, which compete with phenylalanine for transport across the blood-brain barrier, has been demonstrated to be an efficacious treatment for TD. Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Genetic screening of PAH in a group of 123 psychiatric patients revealed ten sequence polymorphisms and two mutations, but none appeared to be a significant risk factor for TD.     

International survey of peritoneal dialysis training programs.

OBJECTIVE: To survey nurses around the world about current practices for peritoneal dialysis (PD) home training programs. DESIGN: Random sampling of nurses to complete a written survey from the International Society for Peritoneal Dialysis Nursing Liaison Committee. Settings: United States, Canada, South America (Brazil, Columbia), The Netherlands, Hong Kong. METHODS: Surveys and responses were sent by fax whenever possible, or by regular mail, or hand carried, or conducted by telephone. Results were stratified by geographic areas as well as by cumulative responses and were expressed as medians with ranges. Kruskal-Wallis was used to evaluate differences in responses. Associations between variables were tested with Pearson correlation. Univariate regression analysis was used to evaluate the impact of variables on peritonitis rates. Variables with p < 0.10 were included in a multivariate analysis. RESULTS: A total of 317 nurses responded: 88 in the United States, 46 in Canada, 58 in South America, 58 in Hong Kong, and 67 in The Netherlands. This represented 37% of all surveys distributed. Respondents had a median of 12 years' experience in nephrology (range 1-35 years), but only 31% had a formal background in adult education. Nearly half received their guidance to patient training from a nurse colleague, 11% were guided by a corporate colleague, and 8% were simply self-taught. Clinics responding had a median of 30 PD patients (range 1-400) and reported they trained a median of 8 patients per year (range 0-86). Reported peritonitis rates were a median 0.46 per year or 1 episode every 26 months. Peritonitis rates, however, were not known by 53% of respondents. Total training time per patient had a very wide range of hours, from 6 to 96. There was no correlation between training time and peritonitis rates among the study respondents (p = 0.38), nor with any other variables. CONCLUSIONS: There is wide variation in practices for PD patient training programs within countries and around the world. Training time did not appear to be related to peritonitis rates. Randomized trials of training practices are needed to determine which approaches produce the best outcomes for patients.     

The Impact of Community Diversity and Consolidated Inequality on Dropping Out of High School

Abstract: Data from the National Education Longitudinal Study were combined with census data at the zip code level to examine the impact of neighborhood racial and ethnic diversity and consolidated inequality, in addition to individual, family, and school factors, on the likelihood of dropping out of high school. Results indicate that while the effects for diversity and consolidated inequality did not support the stated hypotheses, main effects for family risk and prior academic achievement were significant and in the stated direction. Also, when controlling for individual, family, school, and neighborhood characteristics, African Americans were less likely than White students to drop out of school. Implications for contextual effects research and educational outcomes are discussed.     

The expression of emotion through nonverbal behavior in medical visits

Relationship-centered care reflects both knowing and feeling: the knowledge that physician and patient bring from their respective domains of expertise, and the physician’s and patient’s experience, expression, and perception of emotions during the medical encounter. These processes are conveyed and reciprocated in the care process through verbal and nonverbal communication. We suggest that the emotional context of care is especially related to nonverbal communication and that emotion-related communication skills, including sending and receiving nonverbal messages and emotional self-awareness, are critical elements of high-quality care. Although nonverbal behavior has received far less study than other care processes, the current review argues that it holds significance for the therapeutic relationship and influences important outcomes including satisfaction, adherence, and clinical outcomes of care.     

Tungiasis in New York

A 33-year-old African woman was evaluated for tender nodules on her feet. Accompanied by her four children, she had recently immigrated from Somalia. Before her immigration, she resided in a Kenyan refugee camp for approximately 1 year, where she walked barefoot in sand and dirt. The patient stated that she and her four children, as well as many people living in the same compound, had similar, tender lesions on their feet. Her children were "treated" by their grandmother, who removed the contents of their lesions with a safety pin.
On physical examination the patient had numerous tender, isolated, and clustered hyperkeratotic, crusted papules, measuring 4–6 mm, on the plantar and periungual surfaces. Several lesions were ulcerated (Figs 1 and 2). The hyperkeratotic masses were debrided with a surgical blade. An intact, white, coiled structure was curetted from each papule, leaving numerous empty crater-like lesions (Fig. 3), which were identified on histologic sections as Tunga penetrans. Microscopic examination of unstained specimens showed branching, thin, translucent tubular structures with numerous eggs. Ring-shaped cross-sections of the organism's respiratory and digestive tracts were seen on hematoxylin and eosin stain (Fig. 4).
The patient received a 10-day course of dicloxacillin and topical bacitracin ointment. All lesions were healed within 1 week of therapy.     

Acute Leukemia in an Infant with Marfan's Syndrome: A Case Report

We describe a familial case of Marfan's syndrome with associated intrathoracic stomach detected during the neonatal period. The patient developed a primitive leukemia at 3 months of age. Acute leukemia in a patient with Marfan's syndrome has not previously been reported.