Pilot Date on Swallow Function in Nondysphagic Patients Requiring a Tracheotomy Tube

Objective. To evaluate the effects of occlusion status (i.e., open, finger, capped) of the tracheotomy tube and removal of the tracheotomy tube that may have upon bolus flow and durational measurements in nondysphagic persons requiring a tracheotomy tube. Study Design. Prospective, single subject, repeated measure design. Methods. Participants had their swallow evaluated with 5 mL pureed boluses using nasal endoscopy with the tracheotomy tube in place, removed, and under the following occlusion conditions: open, finger, and capped. The order of occlusion condition was randomized. Results. Aspiration was never observed but laryngeal penetration was a common finding. Durational measurements for swallow initiation and duration of white out were not significantly different by occlusion status or after removal of the tracheotomy tube. Conclusion. This study provides corroborating evidence demonstrating the lack of a relationship between a tracheotomy tube and swallowing dysfunction

Utilization and Adherence Patterns of Subcutaneously Administered Anti–Tumor Necrosis Factor Treatment Among Rheumatoid Arthritis Patients

AbstractBackgroundAdherence to therapy is a key requirement underlying achievement of clinical outcomes in randomized controlled drug registration trials. In postmarketing studies, comparison of adherence among therapies can become more complicated when drug dosing and administration schedules differ or when methods used to measure adherence are not consistently applied.ObjectiveThe objective of this exploratory study was to investigate a broad range of utilization and adherence outcomes associated with subcutaneous biologic treatments for rheumatoid arthritis (RA).MethodsAdult patients (aged ≥18 years) exhibiting ≥2 claims with an RA diagnosis (code 714.x), at least 24 months of continuous medical and pharmacy eligibility, and 30-day supplies of adalimumab, etanercept, or golimumab were selected from the Optum Insight Clinformatics database. Adherence and utilization measures were calculated and compared across treatment groups.ResultsA total of 1532 adalimumab, 2099 etanercept, and 261 golimumab patients met inclusion criteria. Compared with both adalimumab and etanercept patients, golimumab patients were significantly more likely to have a medication possession ratio of ≥0.80 (82% vs 71% vs 62%; P < 0.001) and significantly less likely to have ≥4 late medication refills (6.9% vs 17.7% vs 26.1%; P < 0.001 for all). Etanercept patients had significantly greater refill intervals (37.7 vs 34.9 and 35.1 days) and had the lowest proportion of adherent fills (70% vs 77% and 75%) compared with both golimumab and adalimumab patients (P < 0.001 for all). Bivariate effects were reproduced in multivariate models that controlled for treatment duration.ConclusionsA number of statistically significant medication adherence differences were observed among golimumab, adalimumab, and etanercept patients in treatment for RA. Overall, golimumab patients appeared to be the most adherent group. Findings may be partially attributable to golimumab patients’ likely increased disease severity, their prior experience with biologic medication, or golimumab’s once-monthly dosing schedule, which requires fewer administrations than both adalimumab and etanercept

Flue gas injection control of silica in cooling towers.

Injection of CO{sub 2}-laden flue gas can decrease the potential for silica and calcite scale formation in cooling tower blowdown by lowering solution pH to decrease equilibrium calcite solubility and kinetic rates of silica polymerization. Flue gas injection might best inhibit scale formation in power plant cooling towers that use impaired makeup waters - for example, groundwaters that contain relatively high levels of calcium, alkalinity, and silica. Groundwaters brought to the surface for cooling will degas CO{sub 2} and increase their pH by 1-2 units, possibly precipitating calcite in the process. Recarbonation with flue gas can lower the pHs of these fluids back to roughly their initial pH. Flue gas carbonation probably cannot lower pHs to much below pH 6 because the pHs of impaired waters, once outgassed at the surface, are likely to be relatively alkaline. Silica polymerization to form scale occurs most rapidly at pH {approx} 8.3 at 25 C; polymerization is slower at higher and lower pH. pH 7 fluids containing {approx}220 ppm SiO{sub 2} require &gt; 180 hours equilibration to begin forming scale whereas at pH 8.3 scale formation is complete within 36 hours. Flue gas injection that lowers pHs to {approx} 7 should allow substantially higher concentration factors. Periodic cycling to lower recoveries - hence lower silica concentrations - might be required though. Higher concentration factors enabled by flue gas injection should decrease concentrate volumes and disposal costs by roughly half

Selected Toll-like Receptor Ligands and Viruses Promote Helper-Independent Cytotoxic T Cell Priming by Upregulating CD40L on Dendritic Cells

SummaryCD40L (CD154) on CD4+ T cells has been shown to license dendritic cells (DCs) via CD40 to prime cytotoxic T lymphocyte (CTL) responses. We found that the converse (CD40L on DCs) was also important. Anti-CD40L treatment decreased endogenous CTL responses to both ovalbumin and influenza infection even in the absence of CD4+ T cells. DCs expressed CD40L upon stimulation with agonists to Toll-like receptor 3 (TLR3) and TLR9. Moreover, influenza infection, which stimulates CTLs without help, upregulated CD40L on DCs, but herpes simplex infection, which elicits CTLs through help, did not. CD40L-deficient (Cd40lg−/−) DCs are suboptimal both in vivo in bone marrow chimera experiments and in vitro in mixed lymphocyte reactions. In contrast, Cd40lg−/− CD8+ T cells killed as effectively as wild-type cells. Thus, CD40L upregulation on DCs promoted optimal priming of CD8+ T cells without CD4+ T cells, providing a mechanism by which pathogens may elicit helper-independent CTL immunity

Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer

BACKGROUND A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab. METHODS We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival. RESULTS A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progression-free survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P=0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P=0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P=0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P=0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%). CONCLUSIONS Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer

A randomized, comparative pilot trial of family-based interpersonal psychotherapy for reducing psychosocial symptoms, disordered-eating, and excess weight gain in at-risk preadolescents with loss-of-control-eating: SHOMAKER et al.

Preadolescent loss-of-control-eating (LOC-eating) is a risk factor for excess weight gain and binge-eating-disorder. We evaluated feasibility and acceptability of a preventive family-based interpersonal psychotherapy (FB-IPT) program. FB-IPT was compared to family-based health education (FB-HE) to evaluate changes in children’s psychosocial functioning, LOC-eating, and body mass

The Australian Early Years Learning Framework: learning what?

Early childhood education and care have assumed importance in many government policy agendas. This attention is often accompanied by calls for greater accountability regarding the anticipated learning outcomes for young children. In Australia, the expected learning outcomes for children aged birth to five years are outlined in the recently published Early Years Learning Framework (EYLF). In this article, the author examines the relationship between the EYLF’s outcomes and subject area or content knowledge. The article draws from post-structural and social constructionist understandings of knowledge as unfinished, contestable and contextual. The author concludes that it is not content knowledge itself that is problematic, but it is the way the child and teacher are often positioned in relation to that knowledge that constrains the potential for effective teaching and learning in the early years. The author suggests that revisiting traditional assumptions about content knowledge extends and develops many of the ideas about teaching and learning that are identified in the EYLF, and opens up new identity positions for both children and early childhood educators

Viral Endomyocardial Infection Is an Independent Predictor and Potentially Treatable Risk Factor for Graft Loss and Coronary Vasculopathy in Pediatric Cardiac Transplant Recipients

ObjectivesThis study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation.BackgroundViral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survival.MethodsBetween June 1999 and November 2004, 94 pediatric cardiac transplant patients were screened for the presence of viral genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses. From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG) was administered to patients with PCR-positive EMBs. The outcomes of the IVIG-treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR-positive patients (n = 17).ResultsViral genomes were detected in EMBs from 37 (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had decreased graft survival (p < 0.001) compared with the PCR-negative group (n = 57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p = 0.001). The number of AR episodes was similar in both groups. On multivariate analysis, presence of viral genome was an independent risk factor for graft loss (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR-positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward improved graft survival (p = 0.06).ConclusionsViral endomyocardial infection is an independent predictor of graft loss in pediatric cardiac transplant recipients. This effect appears to be mediated through premature development of advanced TCAD. IVIG therapy in this subgroup may improve survival and merits further investigation

A Hypermorphic Missense Mutation in PLCG2, Encoding Phospholipase Cγ2, Causes a Dominantly Inherited Autoinflammatory Disease with Immunodeficiency

Whole-exome sequencing was performed in a family affected by dominantly inherited inflammatory disease characterized by recurrent blistering skin lesions, bronchiolitis, arthralgia, ocular inflammation, enterocolitis, absence of autoantibodies, and mild immunodeficiency. Exome data from three samples, including the affected father and daughter and unaffected mother, were filtered for the exclusion of reported variants, along with benign variants, as determined by PolyPhen-2. A total of eight transcripts were identified as possible candidate genes. We confirmed a variant, c.2120C>A (p.Ser707Tyr), within PLCG2 as the only de novo variant that was present in two affected family members and not present in four unaffected members. PLCG2 encodes phospholipase Cγ2 (PLCγ2), an enzyme with a critical regulatory role in various immune and inflammatory pathways. The p.Ser707Tyr substitution is located in an autoinhibitory SH2 domain that is crucial for PLCγ2 activation. Overexpression of the altered p.Ser707Tyr protein and ex vivo experiments using affected individuals’ leukocytes showed clearly enhanced PLCγ2 activity, suggesting increased intracellular signaling in the PLCγ2-mediated pathway. Recently, our laboratory identified in individuals with cold-induced urticaria and immune dysregulation PLCG2 exon-skipping mutations resulting in protein products with constitutive phospholipase activity but with reduced intracellular signaling at physiological temperatures. In contrast, the p.Ser707Tyr substitution in PLCγ2 causes a distinct inflammatory phenotype that is not provoked by cold temperatures and that has different end-organ involvement and increased intracellular signaling at physiological temperatures. Our results highlight the utility of exome-sequencing technology in finding causal mutations in nuclear families with dominantly inherited traits otherwise intractable by linkage analysis