Surgical Feeding Tubes in Pediatric and Adolescent Cancer Patients: A Single-institution Retrospective Review.

The purpose of our study was to evaluate surgical enteric access in pediatric cancer patients to determine factors associated with postoperative complications. We performed a single-institution retrospective review of all patients below 21 years old with a primary cancer diagnosis who underwent surgical procedures for enteral access between 2004 and 2014. Multivariate logistic regression was performed to determine independent predictors of postoperative complications. During the study period, 122 patients had surgically placed feeding tubes, of whom 58% developed ≥1 complication(s) and 16% experienced a major complication. No single factor was significantly associated with developing any complication or major complication. Several trends were noted including increased complications associated with jejunostomy tubes, percutaneous endoscopic gastrostomy tubes, and abdominal radiation. Surgically placed enteric access in pediatric and adolescent cancer patients is associated with an extremely high complication rate emphasizing the importance of careful evaluation of these patients before embarking on surgical feeding access. Future work should evaluate mechanisms to decrease complications and/or explore alternative methods to provide supplemental nutrition in children and adolescents with cancer.

Caenorhabditis elegans HOPS and CCZ-1 mediate trafficking to lysosome-related organelles independently of RAB-7 and SAND-1.

As early endosomes mature, the SAND-1/CCZ-1 complex acts as a guanine nucleotide exchange factor (GEF) for RAB-7 to promote the activity of its effector, HOPS, which facilitates late endosome-lysosome fusion and the consumption of AP-3-containing vesicles. We show that CCZ-1 and the HOPS complex are essential for the biogenesis of gut granules, cell type-specific, lysosome-related organelles (LROs) that coexist with conventional lysosomes in Caenorhabditis elegans intestinal cells. The HOPS subunit VPS-18 promotes the trafficking of gut granule proteins away from lysosomes and functions downstream of or in parallel to the AP-3 adaptor. CCZ-1 also acts independently of AP-3, and ccz-1 mutants mistraffic gut granule proteins. Our results indicate that SAND-1 does not participate in the formation of gut granules. In the absence of RAB-7 activity, gut granules are generated; however, their size and protein composition are subtly altered. These observations suggest that CCZ-1 acts in partnership with a protein other than SAND-1 as a GEF for an alternate Rab to promote gut granule biogenesis. Point mutations in GLO-1, a Rab32/38-related protein, predicted to increase spontaneous guanine nucleotide exchange, specifically suppress the loss of gut granules by ccz-1 and glo-3 mutants. GLO-3 is known to be required for gut granule formation and has homology to SAND-1/Mon1-related proteins, suggesting that CCZ-1 functions with GLO-3 upstream of the GLO-1 Rab, possibly as a GLO-1 GEF. These results support LRO formation occurring via processes similar to conventional lysosome biogenesis, albeit with key molecular differences.

C. elegans BLOC-1 functions in trafficking to lysosome-related gut granules.

The human disease Hermansky-Pudlak syndrome results from defective biogenesis of lysosome-related organelles (LROs) and can be caused by mutations in subunits of the BLOC-1 complex. Here we show that C. elegans glo-2 and snpn-1, despite relatively low levels of amino acid identity, encode Pallidin and Snapin BLOC-1 subunit homologues, respectively. BLOC-1 subunit interactions involving Pallidin and Snapin were conserved for GLO-2 and SNPN-1. Mutations in glo-2 and snpn-1,or RNAi targeting 5 other BLOC-1 subunit homologues in a genetic background sensitized for glo-2 function, led to defects in the biogenesis of lysosome-related gut granules. These results indicate that the BLOC-1 complex is conserved in C. elegans. To address the function of C. elegans BLOC-1, we assessed the intracellular sorting of CDF-2::GFP, LMP-1, and PGP-2 to gut granules. We validated their utility by analyzing their mislocalization in intestinal cells lacking the function of AP-3, which participates in an evolutionarily conserved sorting pathway to LROs. BLOC-1(-) intestinal cells missorted gut granule cargo to the plasma membrane and conventional lysosomes and did not have obviously altered function or morphology of organelles composing the conventional lysosome protein sorting pathway. Double mutant analysis and comparison of AP-3(-) and BLOC-1(-) phenotypes revealed that BLOC-1 has some functions independent of the AP-3 adaptor complex in trafficking to gut granules. We discuss similarities and differences of BLOC-1 activity in the biogenesis of gut granules as compared to mammalian melanosomes, where BLOC-1 has been most extensively studied for its role in sorting to LROs. Our work opens up the opportunity to address the function of this poorly understood complex in cell and organismal physiology using the genetic approaches available in C. elegans.

Role of the primary care safety net in pandemic influenza.

An influenza pandemic would have a disproportionately adverse impact on minority populations, the poor, the uninsured, and those living in underserved communities. Primary care practices serving the underserved would face special challenges in an influenza pandemic. Although not a formalized system, components of the primary care safety net include federally qualified health centers, public hospital clinics, volunteer or free clinics, and some local public health units. In the event of an influenza pandemic, the primary care safety net is needed to treat vulnerable populations and to provide health care surge capacity to prevent the overwhelming of hospital emergency departments. We examined the strength, capacity, and preparedness of key components of the primary care safety net in responding to pandemic influenza.

Shortages of medical personnel at community health centers: implications for planned expansion.

CONTEXT: The US government is expanding the capacity of community health centers (CHCs) to provide care to underserved populations. OBJECTIVE: To examine the status of workforce shortages that may limit CHC expansion. DESIGN AND SETTING: Survey questionnaire of all 846 federally funded US CHCs that directly provide clinical services and are within the 50 states and the District of Columbia, conducted between May and September 2004. Questionnaires were completed by the chief executive officer of each grantee. Information was supplemented by data from the 2003 Bureau of Primary Health Care Uniform Data System and weighted to be nationally representative. MAIN OUTCOME MEASURES: Staffing patterns and vacancies for major clinical disciplines by rural and urban location, use of federal and state recruitment programs, and perceived barriers to recruitment. RESULTS: Overall response rate was 79.3%. Primary care physicians made up 89.4% of physicians working in the CHCs, the majority of whom are family physicians. In rural CHCs, 46% of the direct clinical providers of care were nonphysician clinicians compared with 38.9% in urban CHCs. There were 428 vacant funded full-time equivalents (FTEs) for family physicians and 376 vacant FTEs for registered nurses. There were vacancies for 13.3% of family physician positions, 20.8% of obstetrician/gynecologist positions, and 22.6% of psychiatrist positions. Rural CHCs had a higher proportion of vacancies and longer-term vacancies and reported greater difficulty filling positions compared with urban CHCs. Physician recruitment in CHCs was heavily dependent on National Health Service Corps scholarships, loan repayment programs, and international medical graduates with J-1 visa waivers. Major perceived barriers to recruitment included low salaries and, in rural CHCs, cultural isolation, poor-quality schools and housing, and lack of spousal job opportunities. CONCLUSIONS: CHCs face substantial challenges in recruitment of clinical staff, particularly in rural areas. The largest numbers of unfilled positions were for family physicians at a time of declining interest in family medicine among graduating US medical students. The success of the current US national policy to expand CHCs may be challenged by these workforce issues.

Management training of physician executives, their leadership style, and care management performance: an empirical study.

OBJECTIVE: To examine associations between management training of physician executives and their leadership styles, as well as effectiveness in achieving disease management goals. STUDY DESIGN: Cross-sectional national survey. METHODS: Executive directors of community health centers (269 respondents; response rate = 40.9%) were surveyed regarding their perceptions of the medical director's leadership, and for quantitative information on the center's achievement of clinical (mostly disease management) goals. The dependent variables were the medical director's scores (as perceived by the executive director) on transformational, transactional, and laissez-faire leadership, effectiveness, satisfaction with the leader, and subordinate extra effort, using an adapted Multifactor Leadership Questionnaire (43 items; 5-point Likert scale). The independent variable was the medical director's management training status. RESULTS: Compared with medical directors with < 30 days of inservice training, medical directors with an MHA, MPH, or MBA, or > or =30 days of in-service training, had 0.32, 0.35, 0.30, 0.36, and 0.37 higher scores on transformational leadership, transactional leadership, rated effectiveness, satisfaction, and subordinate extra effort, respectively, and 0.31 lower score on laissez-faire leadership (all P < .001). Medical directors without management degrees but with > or =30 days of in-service training had 0.34, 0.36, 0.50, and 0.47 higher scores on transformational leadership, transactional leadership, rated effectiveness, and satisfaction with the leader (all P < .02). Our data previously had demonstrated that medical directors' transformational leadership significantly influences achievement of disease management goals. CONCLUSION: Training may enable physician executives to develop leadership styles that are effective in influencing clinical providers' adoption of disease management guidelines under managed care.