American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer

Purpose: To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. Methods: An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. Results: The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. Recommendations: For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.     

Severe hypernatraemia associated with growth hormone replacement therapy in a patient with septo-optic dysplasia

Background The anti-natriuretic properties of growth hormone (GH) are well established. Growth hormone deficiency (GHD) results in salt and water depletion and studies confirm that replacement leads to sodium and vasopressin-mediated water retention in patients with intact posterior pituitary function. Methods We report the case of a 20-year-old male patient with septo-optic dysplasia, fixed cranial diabetes insipidus (DI) and an abnormal thirst threshold. With careful parental support, his sodium levels remained stable for many years on a fixed dose of DDAVP and a supervised fluid intake of 2.5 l/day. Several years after the original diagnosis, he was found to be ACTH deficient and following commencement of hydrocortisone replacement therapy became hypernatraemic. A new sodium homoeostasis was established with a higher dose of DDAVP. Subsequently, he developed symptoms typical of GHD and, after biochemical confirmation, GH replacement was commenced. Results There was an immediate clinical improvement (increased alertness, improved concentration) but severe hypernatraemia developed (peak 169 mmol/l) necessitating revision of his desmopressin and fluid intake regimen. Conclusion Most GHD patients have intact posterior pituitary function. This case report highlights the powerful anti-natriuretic properties of GH. Endocrine physicians should be alert to this in patients with fixed DI and an abnormal thirst threshold.     

Transient Global Amnesia as the Presenting Feature of Heparin‐Induced Thrombocytopenia

Abstract A 57‐year‐old man developed transient global amnesia within an hour of bolus unfractionated heparin administration on day 4 post‐mitral valve replacement. Both immunoglobulin G‐specific enzyme‐linked immunosorbent assay and serotonin release assay were strongly positive for the antibodies that cause heparin‐induced thrombocytopenia. The patient's cognitive functions returned to normal following discontinuation of unfractionated heparin and warfarin and commencement of lepirudin infusion. (J Card Surg 2010;25:300‐302)     

A new evaluation of the upper esophageal sphincter using the functional lumen imaging probe: a preliminary report

Objective and reliable evaluation of upper esophageal sphincter (UES) opening during swallowing based on videofluoroscopy and pharyngeal manometry challenges dysphagia clinicians. The functional lumen imaging probe (FLIP) is a portable tool based on impedance planimetry originally designed to measure esophogastric junction compliance. It is hypothesized that FLIP can evaluate UES distensibility, and can provide UES diameter and pressure measurements at rest, during swallowing, and during voluntary maneuvers. Eleven healthy adult subjects consented to FLIP evaluation. The probe was inserted transorally, and the balloon was positioned across the UES. Two 20‐mL ramp distensions were completed. Changes in UES diameter and intraballoon pressure were measured during dry and 5‐mL liquid swallows, and during voluntary swallow postures and maneuvers employed in clinical practice. The protocol was completed by 10 of 11 healthy subjects. Mean intraballoon pressure increased throughout 5‐mL (5.8 mmHg; ?4.5–18.6 mmHg), 10‐mL (8.7 mmHg; 2.3–28.5 mmHg), 15‐mL (17.3 mmHg; 9.5–34.8 mmHg), and 20‐mL (31.2 mmHg; 16–46.3 mmHg) balloon volumes. Mean resting UES diameter (4.9 mm) increased during dry swallows (9.2 mm) and 5‐mL liquid swallows (7.7 mm). Mean UES diameter increased during 5‐mL liquid swallows with head turn to right (8.1 mm) and left (8.3 mm), chin tuck (8.4 mm), effortful swallow (8.5 mm), Mendelsohn maneuver (8.1 mm), and supraglottic swallow (7.8 mm). FLIP was safely inserted and distended in the UES, and provided useful quantitative data regarding UES distensibility and UES diameter changes during swallowing maneuvers. Further research is being conducted to explore the role of FLIP in UES evaluation.     

A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion

BACKGROUND: Cervical cancer is caused by persistent infection with human papillomavirus (HPV). Most infections and associated lesions clear spontaneously. It is important to define the determinants and timing of clearance, so that viral persistence can be recognized and managed. METHODS: We investigated HPV natural history among 4504 subjects from ALTS (Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study). A discrete-time Markov model was used to simultaneously describe the prevalence, incidence, and persistence of type-specific HPV infection over 24 months in women with equivocal or mildly abnormal cytological results. Interactions between multiple HPV types infecting the same woman were examined for incidence of new infection (after an HPV-16 infection) and persistence of a current infection within groups defined by phylogenetic relatedness or by carcinogenicity. RESULTS: Ninety-one percent (95% credible interval [CI], 90%-92%) of prevalent HPV infections at enrollment cleared within 24 months. The probability that an infection would persist for a further 6 months increased with the duration of infection, from 37% (95% CI, 35%-39%) for a newly observed infection to 65% (95% CI, 61%-70%) for an infection that had already persisted for > or =18 months. No consistent evidence of interactions was found between multiple HPV types regarding the incidence of new infection after an HPV-16 infection or regarding persistence of current HPV infection. CONCLUSION: Although virtually all HPV infections clear within 2 years, the remaining infections have a high potential for persistence and, by implication, progression to precancer and cancer. Once biological and behavioral determinants are controlled for, HPV infections with different types seem to be independent of each other.     

Developing and testing a measure of dyadic efficacy for married women with rheumatoid arthritis and their spouses

OBJECTIVE: Interpersonal relationships and self-efficacy have each been independently studied in the context of coping with chronic illness. To examine a new type of interpersonal efficacy in couples coping with rheumatoid arthritis (RA), we developed and tested new measures of perceptions of arthritis dyadic efficacy. We assessed both partners' perceptions of confidence about working together as a team to manage women's illness-related challenges. METHODS: First, a 3-phase pilot study was conducted with interviews, expert review, and pretesting to develop items. Next, the psychometric properties of new measures were tested in 190 women with RA and their husbands. Exploratory analyses were conducted, Cronbach's alphas were calculated for each factor, and construct validity was examined with Pearson's correlations at baseline, 4-month, and 8-month followup. RESULTS: Factor analyses yielded 3 factors in the wife and husband versions, assessing dyadic behaviors concerning arthritis problem solving and emotions, arthritis symptom management, and arthritis-related couple outcomes. All items loaded >0.60, Cronbach's alphas for all subscales were >0.88, and initial evidence of construct validity was demonstrated. Finally, the initial factor structure was replicated with additional exploratory factor analyses in the same sample at 4-month and 8-month followup. CONCLUSION: Three short, reliable subscales resulted for couples coping with RA for use in interpersonal health research. These instruments facilitate viewing illness adaptation processes in a dyadic manner.