Publications

Neurofibromatosis type 1 (NF1) is a common, dominantly inherited genetic disorder that results from mutations in the neurofibromin 1 (NF1) gene. Affected individuals demonstrate abnormalities in neural-crest-derived tissues that include hyperpigmented skin lesions and benign peripheral nerve sheath tumors. NF1 patients also have a predisposition to malignancies including juvenile myelomonocytic leukemia (JMML), optic glioma, glioblastoma, schwannoma and malignant peripheral nerve sheath tumors (MPNSTs). In an effort to better define the molecular and cellular determinants of NF1 disease pathogenesis in vivo, we employed targeted mutagenesis strategies to generate zebrafish harboring stable germline mutations in nf1a and nf1b, orthologues of NF1. Animals homozygous for loss-of-function alleles of nf1a or nf1b alone are phenotypically normal and viable. Homozygous loss of both alleles in combination generates larval phenotypes that resemble aspects of the human disease and results in larval lethality between 7 and 10 days post fertilization. nf1-null larvae demonstrate significant central and peripheral nervous system defects. These include aberrant proliferation and differentiation of oligodendrocyte progenitor cells (OPCs), dysmorphic myelin sheaths and hyperplasia of Schwann cells. Loss of nf1 contributes to tumorigenesis as demonstrated by an accelerated onset and increased penetrance of high-grade gliomas and MPNSTs in adult nf1a(+/-); nf1b(-/-); p53(e7/e7) animals. nf1-null larvae also demonstrate significant motor and learning defects. Importantly, we identify and quantitatively analyze a novel melanophore phenotype in nf1-null larvae, providing the first animal model of the pathognomonic pigmentation lesions of NF1. Together, these findings support a role for nf1a and nf1b as potent tumor suppressor genes that also function in the development of both central and peripheral glial cells as well as melanophores in zebrafish.

BACKGROUND

Point-of-care electronic medical records (EMRs) are a key tool to manage chronic illness. Several EMRs have been developed for use in treating HIV and tuberculosis, but their applicability to primary care, technical requirements and clinical functionalities are largely unknown.

OBJECTIVES

This study aimed to address the needs of clinicians from resource-limited settings without reliable internet access who are considering adopting an open-source EMR.

STUDY ELIGIBILITY CRITERIA

Open-source point-of-care EMRs suitable for use in areas without reliable internet access.

STUDY APPRAISAL AND SYNTHESIS METHODS

The authors conducted a comprehensive search of all open-source EMRs suitable for sites without reliable internet access. The authors surveyed clinician users and technical implementers from a single site and technical developers of each software product. The authors evaluated availability, cost and technical requirements.

RESULTS

The hardware and software for all six systems is easily available, but they vary considerably in proprietary components, installation requirements and customisability.

LIMITATIONS

This study relied solely on self-report from informants who developed and who actively use the included products.

CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS

Clinical functionalities vary greatly among the systems, and none of the systems yet meet minimum requirements for effective implementation in a primary care resource-limited setting. The safe prescribing of medications is a particular concern with current tools. The dearth of fully functional EMR systems indicates a need for a greater emphasis by global funding agencies to move beyond disease-specific EMR systems and develop a universal open-source health informatics platform.

CONTEXT

Some veterans are eligible to enroll simultaneously in a Medicare Advantage (MA) plan and the Veterans Affairs health care system (VA). This scenario produces the potential for redundant federal spending because MA plans would receive payments to insure veterans who receive care from the VA, another taxpayer-funded health plan.

OBJECTIVE

To quantify the prevalence of dual enrollment in VA and MA, the concurrent use of health services in each setting, and the estimated costs of VA care provided to MA enrollees.

DESIGN

Retrospective analysis of 1,245,657 veterans simultaneously enrolled in the VA and an MA plan between 2004-2009.

MAIN OUTCOME MEASURES

Use of health services and inflation-adjusted estimated VA health care costs.

RESULTS

Among individuals who were eligible to enroll in the VA and in an MA plan, the number of persons dually enrolled increased from 485,651 in 2004 to 924,792 in 2009. In 2009, 8.3% of the MA population was enrolled in the VA and 5.0% of MA beneficiaries were VA users. The estimated VA health care costs for MA enrollees totaled $13.0 billion over 6 years, increasing from $1.3 billion in 2004 to $3.2 billion in 2009. Among dual enrollees, 10% exclusively used the VA for outpatient and acute inpatient services, 35% exclusively used the MA plan, 50% used both the VA and MA, and 4% received no services during the calendar year. The VA financed 44% of all outpatient visits (n = 21,353,841), 15% of all acute medical and surgical admissions (n = 177,663), and 18% of all acute medical and surgical inpatient days (n = 1,106,284) for this dually enrolled population. In 2009, the VA billed private insurers $52.3 million to reimburse care provided to MA enrollees and collected $9.4 million (18% of the billed amount; 0.3% of the total cost of care).

CONCLUSIONS

The federal government spends a substantial and increasing amount of potentially duplicative funds in 2 separate managed care programs for the care of same individuals.

PURPOSE

We report our experience and present our technique with the robot-assisted laparoscopic ipsilateral ureteroureterostomy (IUU) in the management of ureteral duplication with ectopia in children.

PATIENTS AND METHODS

We reviewed our institutional experience for all patients who underwent a robot-assisted laparoscopic IUU at the University of Minnesota Amplatz Children's Hospital between December 2010 and October 2011. An intraoperative, three-port technique was used after a ureteral stent was placed into the ipsilateral lower pole. Demographic information, diagnosis, operative time, hospital course, complications, and follow-up were all evaluated.

RESULTS

Our series included four female patients and one male patient with a mean age of 61 months (6 to 182 mos). All five had a diagnosis of upper pole ectopic ureters, one of which was associated with an ureterocele. Mean total operative time was 225 minutes (181 to 253 min), and mean hospital stay was 1.2 days (1-2 days). There were no intraoperative complications. In follow-up, at the time of ureteral stent removal, pyelonephritis developed in one patient, but all patients had resolution of their presenting symptoms including urinary tract infections and incontinence. A significant reduction in upper pole hydronephrosis was seen in all patients.

CONCLUSIONS

Our experience indicates that robot-assisted laparoscopic IUU is safe and effective in the management of ureteral duplication anomalies in children.