Intensified Daily Dialysis: The Best Chronic Dialysis Option for Children?

Children receiving chronic hemodialysis (HD) three times a week have many obstacles to overcome. Not only do they have to endure dietary restrictions, but they also need to take various medications on a daily basis, which contribute to anorexia. Children on such conventional dialysis programs often have poorly controlled blood pressure (which can lead to left ventricular hypertrophy and/or left ventricular dysfunction) and impaired statural growth. Therefore, the need for more frequent and/or intensive dialysis is recognized. Nevertheless despite limited center experience, daily dialysis is currently most often limited as a rescue treatment. When performed, daily intensified HD provides a modality for preserving cardiovascular health and promoting normal growth in children. Therefore, the time spent on chronic dialysis preserves their chances of the best possible outcome.     

Emergency department management of sexually transmitted infections

Patients seeking treatment for sexually transmitted infections (STIs) account for a large number of emergency department (ED) visits per year. Despite the large volume of patients, STIs are often missed or treated inappropriately. Due to the high prevalence and incidence of STIs in the United States, it is important that emergency practitioners recognize symptoms consistent with STIs, and treat presumptively. This practice leads to overtreatment of STIs; however, when weighed against the public health risk and complications of untreated disease, empiric treatment is recommended. This article provides an overview of STIs encountered in the ED and recommendations for their treatment.     

Xenografts of highly resistant leukemia recapitulate the clonal composition of the leukemogenic compartment

Clonal evolution of the leukemogenic compartment may contribute to alter the therapeutic response in acute lymphoblastic leukemia (ALL). Using xenotransplantation of primary leukemia cells, we evaluated the phenotypic and genetic composition of de novo resistant very high risk precursor B-cell ALL, a subgroup defined by the persistence of minimal residual disease despite intensive chemotherapy. Analysis of copy number alterations (CNAs) showed that the xenografted leukemia, even when reconstituted from 100 cells, remained highly related to the diagnostic sample, with minor changes in CNAs, mostly deletions, emerging in most cases in the first passage into mice. At the single-cell level, the pattern of monoallelic and biallelic deletions of the CDKN2A locus revealed distinct leukemia subpopulations, which were reproducibly tracked in xenografts. In most very high risk ALL cases, the predominant diagnostic clones were reconstituted in xenografts, as shown by multiplex polymerase chain reaction analysis of immunoglobulin and T-cell receptor loci. In other cases, the pattern in CNAs and immunoglobulin and T-cell receptor rearrangement was less concordant in xenografts, suggesting the outgrowth of subclones. These results unequivocally demonstrate the existence of clonally closely related but distinct subsets of leukemia initiating cells in ALL, which has important implications for drug development and preclinical disease modeling.     

Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score

The outcome of chronic myeloid leukemia (CML) has been profoundly changed by the introduction of tyrosine kinase inhibitors into therapy, but the prognosis of patients with CML is still evaluated using prognostic scores developed in the chemotherapy and interferon era. The present work describes a new prognostic score that is superior to the Sokal and Euro scores both in its prognostic ability and in its simplicity. The predictive power of the score was developed and tested on a group of patients selected from a registry of 2060 patients enrolled in studies of first-line treatment with imatinib-based regimes. The EUTOS score using the percentage of basophils and spleen size best discriminated between high-risk and low-risk groups of patients, with a positive predictive value of not reaching a CCgR of 34%. Five-year progression-free survival was significantly better in the low- than in the high-risk group (90% vs 82%, P = .006). These results were confirmed in the validation sample. The score can be used to identify CML patients with significantly lower probabilities of responding to therapy and survival, thus alerting physicians to those patients who require closer observation and early intervention.     

Mobile uterine retroversion is associated with dyspareunia and dysmenorrhea in an unselected population of women

OBJECTIVE: To determine if isolated retroversion is a cause of pelvic pain symptoms. STUDY DESIGN: One hundred and eleven premenopausal women consulting for routine examination in the gynecology department of two hospitals and two gynecologic private practices were evaluated for chronic pelvic pain symptoms with a self-administered questionnaire. Uterine position and mobility was assessed by pelvic examination. Women with fixed uterus were excluded. RESULTS: Twenty-seven women (24.3%) had a retroverted uterus, and 84 (75.7%) had an anteverted or intermediate uterus. Uterine retroversion was associated with a higher prevalence of dyspareunia (66.7% versus 42.1%, p=0.03), a higher visual analogue scale score for dyspareunia (2.7+/-2.6 versus 1.6+/-2.4, p=0.04) and a higher prevalence of severe dysmenorrhea (66.7% versus 42.9% p=0.03). There was no association between uterine retroversion and noncyclic pain, ovulation pain, or premenstrual pain. CONCLUSION: Mobile uterine retroversion is associated with dyspareunia and dysmenorrhea in a population of unselected women.     

The Absolute Oral Bioavailability and Population-Based Pharmacokinetic Modelling of a Novel Dipeptidylpeptidase-IV Inhibitor,Vildagliptin, in Healthy Volunteers

BACKGROUND AND OBJECTIVE: Vildagliptin is a potent, selective, orally active inhibitor of dipeptidylpeptidase-IV being developed for the treatment of type 2 diabetes mellitus. The objective of this study was to assess the absolute oral bioavailability of vildagliptin by comparing the systemic exposure after oral and intravenous administration in healthy volunteers. METHODS: This was an open-label, randomised, two-period, two-treatment, crossover study in 11 healthy volunteers. Subjects received vildagliptin 50mg orally or 25mg as a 30-minute intravenous infusion on two occasions separated by a 72-hour washout period. Vildagliptin concentrations were determined by a specific assay in urine (lower limit of quantification [LLQ] = 5 ng/mL) and serial plasma samples (LLQ = 2 ng/mL) obtained up to 24 hours after dosing. Noncompartmental analysis and population pharmacokinetic modelling were performed. RESULTS: Both noncompartmental analysis and population pharmacokinetic modelling estimated the absolute oral bioavailability of vildagliptin to be 85%. Renal elimination of unchanged vildagliptin accounted for 33% and 21% of the administered dose 24 hours after intravenous and oral administration, respectively. Renal clearance (13 L/h) was approximately one-third of the total systemic clearance (41 L/h). Two peaks were observed in plasma concentrations at 1 and 3 hours after oral administration in nine of 11 subjects. Modelling based on the population approach identified two absorption sites with lag-times of 0.225 and 2.46 hours. Both absorption rate constants were slower than the elimination rate constant, indicating 'flip-flop' kinetics after oral administration. Bodyweight was identified as a factor with an impact on the volume of distribution of the peripheral compartment. Clearance was 24% greater in males (44.6 L/h) than in females (36.1 L/h). CONCLUSIONS: Vildagliptin is rapidly and well absorbed with an estimated absolute bioavailability of 85%. Two possible sites of absorption were identified, and the absorption rates were slower than the elimination rate, indicating a flip-flop phenomenon after oral dosing.     

Characteristics of representative payeeship involving families of beneficiaries with psychiatric disabilities

OBJECTIVE: Although the Social Security Administration frequently assigns family members to serve as representative payees for relatives with psychiatric disabilities, few studies have examined characteristics associated with these payee arrangements or the perceptions of the individuals involved in them. METHODS: One hundred participants (50 dyads of consumers with psychiatric disabilities and their representative payees from their family) were interviewed for data on perceived benefits and problems of the payeeship, knowledge of payee guidelines, the consumer-payee relationship, arithmetic and money management skills, and payeeship characteristics. RESULTS: Most consumers and payees believed that payeeship led to greater living stability; however, 36% of consumers and 50% of payees reported disagreement and conflict. Some consumers thought payeeship reduced their autonomy, although payees were less aware of this. Consumers and payees showed gaps in knowledge of payeeship, with only 28% correctly recognizing that payeeship did not last indefinitely. Both groups showed deficiencies in money management skills and basic arithmetic abilities; in these domains, there were no significant differences between payees and consumers. Risk of conflict was elevated when consumers had better money management skills and when payees had not completed high school. CONCLUSIONS: Although payeeship was beneficial, the data revealed potential problems in skills and knowledge about representative payeeship among consumers and payees. Efforts by policy makers and clinicians to increase collaboration between payees and consumers and to improve accurate knowledge of payeeship could help address its downsides.     

Developing a general population job-exposure matrix in the absence of sufficient exposure monitoring data

In New Zealand, there is a need for a comprehensive and accessible database with national occupational exposure information, such as a general population job-exposure matrix (GPJEM). However, few New Zealand-specific exposure data exist that could be used to construct such a GPJEM. Here, we present the methods used to develop a GPJEM for New Zealand (NZJEM), by combining GPJEMs from other countries with New Zealand-specific exposure information, using wood dust as an example to illustrate this process. The assessments of GPJEMs from other countries were made available to a New Zealand expert in occupational wood dust exposure, who then provided a preliminary NZJEM assessment (including the percentage exposed and the level of exposure for each occupation). Where possible, this assessment was based on New Zealand exposure measurements. In the next step, information from a nationwide workplace exposure survey of 3000 members of the New Zealand workforce was used to finalize the NZJEM assessments. The final NZJEM listed 104 of the 956 New Zealand occupational codes as exposed to wood dust. The percentage of workers exposed within an occupation ranged from 5% (e.g. boiler attendants) to 100% (e.g. cabinet makers). The level of exposure ranged from 0.05 mg m(-3) (e.g. electricians) to 3 mg m(-3) (e.g. carpenters). Of these assessments, 23% were mainly based on New Zealand exposure data, 37% on overseas GPJEMs and exposure data, and for 40% the national survey data served as the main source of information for the expert assessment. Combining the NZJEM assessments with national employment statistics indicated that 5.6% of the New Zealand workforce is occupationally exposed to wood dust, corresponding to a total of 97 000 workers (86% male and 14% female). Construction-related occupations included the largest number of exposed workers.