Heat and moisture exchanger cassettes: Results of a quality/safety initiative to reduce postoperative mucus plugging after total laryngectomy.

BACKGROUND: Tracheal dryness is a concern after total laryngectomy due to the potential for mucus plugs (MP). This study compared heat and moisture exchanger (HME) cassettes to external tracheal humidification (ETH) surrounding MP events. METHODS: A retrospective comparative cohort study comparing outcomes before/after implementation of a patient safety initiative utilizing HME during post laryngectomy hospitalization. The number of MP events were compared with a pre-implementation control group using ETH. Patient characteristics were analyzed for correlation with MP. RESULTS: The rate of MP was significantly lower in the HME group than ETH (0.13 and 0.38 per 10 inpatient days, respectively, P = .02). The proportion of patients with one or more MP events was also significantly reduced in the HME group (50% ETH and 11% HME, P = .01). Method of humidification was the only significant variable associated with MP on logistic regression modeling (P = .008). CONCLUSIONS: HMEs were superior to ETH for prevention of MP.

The Influence of Occupation on Self-perceived Vocal Problems in Patients With Voice Complaints.

OBJECTIVE: This study aimed to examine the relationships among patient occupation, laryngeal diagnosis, perceptual dysphonia severity, and patient-perceived voice impairment. METHODS: Adult patients presenting with a chief complaint of dysphonia over a 20-month period at a tertiary care, interdisciplinary voice center were included in this retrospective cohort study. Patients were categorized by profession: vocal performers, high occupational voice demand, low or no occupational voice demand, and retired. Associations between professional voice demand and clinician rating of dysphonia severity using the "Grade" score from the Grade, Roughness, Breathiness, Asthenia, and Strain scale and patient ratings of voice impairment using the Voice Handicap Index-10 (VHI-10) were tested using standard descriptive statistical methods. RESULTS: One hundred and sixty-three patients with a presenting complaint of dysphonia were evaluated. Significant associations were found on univariate and multivariable analysis among a patient's occupational voice demand, Grade, Roughness, Breathiness, Asthenia, and Strain grade, and VHI-10 score (P = 0.007 and P < 0.001, respectively). Patients subject to greater vocal demands as a result of their occupation had a greater perception of impairment, regardless of acoustic-perceptual severity, when compared with those with low or no occupational voice demand. Although voice diagnosis was significantly associated with VHI-10 score on univariate analysis, it failed to reach significance on multivariable analysis. Demographic measures such as gender and age also did not correlate with perceived vocal impairment. CONCLUSION: Patient-perception of voice impairment is influenced by occupational demand, independent of acoustic-perceptual dysphonia. Performers and people with high occupational voice needs demonstrate a unique sensitivity to subtle voice changes.

The Role of Occupational Voice Demand and Patient-Rated Impairment in Predicting Voice Therapy Adherence.

OBJECTIVE: Examine the relationship among the severity of patient-perceived voice impairment, perceptual dysphonia severity, occupational voice demand, and voice therapy adherence. Identify clinical predictors of increased risk for therapy nonadherence. METHODS: A retrospective cohort study of patients presenting with a chief complaint of persistent dysphonia at an interdisciplinary voice center was done. The Voice Handicap Index-10 (VHI-10) and the Voice-Related Quality of Life (V-RQOL) survey scores, clinician rating of dysphonia severity using the Grade score from the Grade, Roughness Breathiness, Asthenia, and Strain scale, occupational voice demand, and patient demographics were tested for associations with therapy adherence, defined as completion of the treatment plan. Classification and Regression Tree (CART) analysis was performed to establish thresholds for nonadherence risk. RESULTS: Of 166 patients evaluated, 111 were recommended for voice therapy. The therapy nonadherence rate was 56%. Occupational voice demand category, VHI-10, and V-RQOL scores were the only factors significantly correlated with therapy adherence (P < 0.0001, P = 0.018, and P = 0.008, respectively). CART analysis found that patients with low or no occupational voice demand are significantly more likely to be nonadherent with therapy than those with high occupational voice demand (P < 0.001). Furthermore, a VHI-10 score of ≤29 or a V-RQOL score of >40 is a significant cutoff point for predicting therapy nonadherence (P < 0.011 and P < 0.004, respectively). CONCLUSION: Occupational voice demand and patient perception of impairment are significantly and independently correlated with therapy adherence. A VHI-10 score of ≤9 or a V-RQOL score of >40 is a significant cutoff point for predicting nonadherence risk.

Impact of baseline patient-reported dysphagia on acute gastrostomy placement in patients with head and neck squamous cell carcinoma undergoing definitive radiation.

BACKGROUND: Dysphagia-related symptoms in patients with head and neck cancer are common before treatment. We hypothesized greater self-reported baseline dysphagia would predict gastrostomy placement during primary radiation. METHODS: Swallowing-specific/general surveys (SwalQOL/EuroQOL) collected prospectively before definitive radiation were analyzed for associations with gastrostomy placement. Prophylactic gastrostomy was recommended at the discretion of a multidisciplinary team blinded to the surveys. RESULTS: Of 84 patients in the cohort, 42 patients (50%) received feeding tubes. Eleven patients (13%) who underwent prophylactic feeding tube placement reported the greatest pretreatment dysphagia, whereas those who avoided gastrostomies reported the least. Prophylactic gastrostomy was more strongly associated with patient-reported measures than other clinical criteria. Controlling for stage IV, T3 to T4 classification, smoking, chemotherapy, and pretreatment weight loss, baseline dysphagia remained an independent predictor of feeding tube placement (odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.05-0.55; p = .01). Patients without gastrostomies during treatment avoided persistent gastrostomy dependence. CONCLUSION: Baseline dysphagia-related symptoms before radiation are independent predictors of gastrostomy placement. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1318-E1324, 2016.

Readmission Patterns and Effectiveness of Transitional Care Among Medicaid Patients With Schizophrenia and Medical Comorbidity.

BACKGROUND: Patients with chronic medical and mental health comorbidities are at increased risk of hospital admission, but little is known about their hospital utilization patterns or whether nurse-directed transitional care interventions have any appreciable impact on future hospitalizations. METHOD: Using paid Medicaid claims and a care management database, we examined patterns of hospital utilization for adults with multiple chronic conditions where one of the conditions was schizophrenia. Patients were enrolled in Community Care of North Carolina's medical home program and were discharged from 100 different hospitals throughout the state from July 1, 2010 through June 30, 2011. We examined readmission rates after psychiatric and nonpsychiatric hospital discharges, and we compared patients who received community-based, nurse-directed, transitional care management services to patients who received usual care. RESULTS: A total of 1,717 patients were included in the final analysis. Patients in this study experienced 980 readmissions over the course of 1 year, with 20% of readmissions for a different reason than the primary hospitalization, and 36% of readmissions occurring at a different hospital. Controlling for demographic, clinical, and hospital characteristics, patients receiving transitional care (n = 1,104) were as much as 30% less likely to experience a readmission during the year following discharge compared to patients receiving usual care (n = 613). LIMITATIONS: This descriptive study reports on a nonrandomized intervention and its impact on service utilization for Medicaid patients with complex illnesses in North Carolina. CONCLUSIONS: Regardless of the reason for hospitalization, patients with chronic medical and psychiatric conditions may benefit from transitional care support that addresses both conditions. This holds true even when the patient is already receiving intensive outpatient psychiatric care.

Baseline health perceptions, dysphagia, and survival in patients with head and neck cancer.

BACKGROUND: In head and neck cancer patients prior to treatment, dysphagia noted by patients is more common than aspiration on formal swallow studies. The authors hypothesized that patient-reported dysphagia impacts multiple domains of quality of life (QOL) and predicts disease recurrence and disease-related death. METHODS: The Swal-QOL, a dysphagia-specific, swallowing-related, QOL measure, and the EuroQOL-5D-3L were administered to 159 patients before treatment with curative intent in this prospective cohort study. Logistic regression analysis evaluated associations among clinical and subjective measures. Multivariable competing risk regression tested the impact of clinical, tumor, and patient-reported measures on survival. RESULTS: Baseline dysphagia, pain, and diminished patient-reported health state were found to be closely associated with weight loss before treatment and advanced T classification. However, only 58% of patients (23 of 40 patients) reporting dysphagia experienced > 5% weight loss. Dysphagia was found to be associated with pain and/or diminished patient-reported health state, independent of weight loss. Female patients were more likely to report pain and dysphagia, whereas male patients reported dysphagia alone. Dysphagia was found to be predictive of disease recurrence and disease-related death, adjusting for T and N classifications, ECOG performance status, smoking status, and weight loss, and accounting for competing risks of death (recurrence-free survival: hazards ratio, 3.8 [95% confidence interval, 1.7-8.4; P = .001] and disease-related death: hazards ratio, 4.2 [95% confidence interval, 1.04-5; P = .004]). CONCLUSIONS: Baseline dysphagia affects multiple domains of QOL and general health perceptions in patients with head and neck cancer prior to treatment. A dysphagia measure captures the effort of maintaining nutrition, and identifies patients predisposed to disease recurrence and disease-related death.

Uptake of calcium phosphate nanoshells by osteoblasts and their effect on growth and differentiation.

The influence of calcium phosphate nanoshell materials on the uptake, viability, and mineralization of human fetal osteoblast cultures was evaluated. Proliferation rates and alkaline phosphatase activity of the cultures were unaffected by the addition of nanoshells to the growth media, but mineralization levels were enhanced by nearly 40%, in contrast to media prepared without nanoshells, or with other calcium phosphate nanomaterials. Nanoshells were internalized by macropinocytosis, and migrated toward the cell nucleus at a rate of 0.34 microm hr(-1). Dye-loaded nanoshells maintained high light emission intensity for over five days while inside the cells, where they could be used as intracellular markers for in vitro microscopic imaging. From these results, it appears that the CaP nanoshells could be developed into a safe sensor and delivery vehicle for osteoblast cell culture studies, whereas the carrier itself has intrinsic bioactivity and may itself upregulate the formation of new bone.

Elicited antibodies in baboons exposed to tissues from alpha1,3-galactosyltransferase gene-knockout pigs.

BACKGROUND: This study investigates anti-nonGal antibodies (Abs) in baboons after alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pig heart transplantation (Tx). METHODS: Four baboons underwent pig heart Tx under chronic immunosuppression, which was discontinued after graftectomy. During follow-up, one baboon also received a pig splenocyte infusion. Hearts and splenocytes were from GalT-KO pigs (n = 3) or pigs with low Gal expression (Gal-low, n = 2), all of swine leukocyte antigen (SLA) dd haplotype. Several weeks after graftectomy, sera were tested by flow cytometry and cytotoxicity assay on porcine peripheral blood mononuclear cells (PBMC) for elicited anti-nonGal Abs. Sera were adsorbed on a Gal immunoaffinity matrix, and tested for SLA haplotype specificity using PBMC from SLA aa, cc, and dd haplotypes. RESULTS: Before heart Tx, no baboon had anti-nonGal Abs demonstrable by binding or cytotoxicity to GalT-KO PBMC. All four baboons developed anti-nonGal Abs after Tx, demonstrable by flow cytometry, and three sera from baboons showed cytotoxicity to GalT-KO PBMC of SLA(dd) haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLA(dd), SLA(aa), SLA(cc)). CONCLUSIONS: Anti-nonGal Abs developed after GalT-KO pig heart Tx into baboons. The most potent of these antibodies appeared to detect antigens shared by the three pig haplotypes tested. It remains unclear whether these antibodies are directed towards shared SLA determinants or other pig antigens, and whether antibodies with specificity for allelic SLA determinants are also present, but at lower titer.

Being bad isn't always good: affective context moderates the attention bias toward negative information.

Research has demonstrated that people automatically devote more attention to negative information than to positive information. The authors conducted 3 experiments to test whether this bias is attenuated by a person's affective context. Specifically, the authors primed participants with positive and negative information using traditional (e.g., subliminal semantic priming) and nontraditional (e.g., social interactions) means and measured the amount of attention they allocated to positive and negative information. With both event-related brain potentials (Experiment 1) and the Stroop task (Experiments 2 and 3), results suggest that the attention bias to negative information is attenuated or eliminated when positive constructs are made accessible. The implications of this result for other biases to negative information and for the self-reinforcing nature of emotional disorders are discussed.

Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates.

Cell-based diabetes therapy requires an abundant cell source. Here, we report reversal of diabetes for more than 100 d in cynomolgus macaques after intraportal transplantation of cultured islets from genetically unmodified pigs without Gal-specific antibody manipulation. Immunotherapy with CD25-specific and CD154-specific monoclonal antibodies, FTY720 (or tacrolimus), everolimus and leflunomide suppressed indirect activation of T cells, elicitation of non-Gal pig-specific IgG antibody, intragraft expression of proinflammatory cytokines and invasion of infiltrating mononuclear cells into islets.

Platelet FcgammaRIIA expression is associated with the alpha2 integrin C807T gene polymorphism in type 2 diabetes.

"Patelet" FcgammaRIIA is stably overexpressed in type 2 diabetes and may also play a role in collagen-mediated platelet activation. Platelet surface integrin a(2)ss(1)-collagen interaction is an early step associated with platelet adhesion and activation and plays an important role in arterial thrombosis. The objective of this study was to characterize the relationship in diabetes and non-diabetes platelets between FcgammaRIIA expression and a polymorphism associated with arterial thrombotic events, polymorphism C807T on the gene encoding a(2)ss(1). Platelet flow cytometry and allele-specific PCR revealed a significant correlation in type 2 diabetes between low platelet FcgammaRIIA expression and the 807TT genotype that is associated with increased platelet a(2)ss(1) receptor density. We conclude that uni- or bi-directional modulation of surface expression may exist between the platelet FcgammaRIIA receptor and a a(2)ss(1) thrombogenic polymorphism that could play a role in platelet sensitivity to collagen in type 2 diabetes.

Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience.

Hearts from alpha1,3-galactosyltransferase knockout pigs (GalT-KO, n = 8) were transplanted heterotopically into baboons using an anti-CD154 monoclonal antibody-based regimen. The elimination of the galactose-alpha1,3-galactose epitope prevented hyperacute rejection and extended survival of pig hearts in baboons for 2-6 months (median, 78 d); the predominant lesion associated with graft failure was a thrombotic microangiopathy, with resulting ischemic injury. There were no infectious complications directly related to the immunosuppressive regimen. The transplantation of hearts from GalT-KO pigs increased graft survival over previous studies.

alpha1,3-Galactosyltransferase gene-knockout miniature swine produce natural cytotoxic anti-Gal antibodies.

BACKGROUND: The expression of galactose alpha 1,3 galactose (Gal) in pigs has proved a barrier to xenotransplantation. Miniature swine lacking Gal (Gal pigs) have been produced by nuclear transfer/embryo transfer. METHODS: The tissues of five Gal pigs of SLA dd haplotype (SLA) were tested for the presence of Gal epitopes by staining with the Griffonia simplicifolia IB4 lectin. Their sera were tested by flow cytometry for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from wild-type (Gal) SLA-matched pigs; serum cytotoxicity was also assessed. The cellular responses of PBMC from Gal swine toward Gal SLA-matched PBMC were tested by mixed leukocyte reaction and cell-mediated lympholysis assays. RESULTS: None of the tissues tested showed Gal expression. Sera from all five Gal pigs manifested IgM binding to Gal pig PBMC, and sera from three showed IgG binding. In all five cases, cytotoxicity to Gal cells could be demonstrated, which was lost after treatment of the sera with dithiothreitol, indicating IgM antibody-mediated cytotoxicity. PBMC from Gal swine had no proliferative or cytolytic T-cell response toward Gal SLA-matched PBMC. CONCLUSIONS: Gal pigs do not express Gal epitopes and develop anti-Gal antibodies that are cytotoxic to Gal pig cells. The absence of an in vitro cellular immune response between Gal and Gal pigs is related to their identical SLA haplotype and indicates the absence of immunogenicity of Gal in T-cell responses. The model of Gal organ transplantation into a Gal SLA-matched recipient would be a valuable large animal model in the study of accommodation or B-cell tolerance.

Porcine endogenous retrovirus transmission characteristics of galactose alpha1-3 galactose-deficient pig cells.

Galactose alpha1-3 galactose (Gal) trisaccharides are present on the surface of wild-type pig cells, as well as on viruses particles produced from such cells. The recognition of Gal sugars by natural anti-Gal antibodies (NAb) in human and Old World primate serum can cause the lysis of the particles via complement-dependent mechanisms and has therefore been proposed as an important antiviral mechanism. Recently, pigs have been generated that possess disrupted galactosyl-transferase (GGTA1) genes. The cells of these pigs do not express Gal sugars on their surface, i.e., are Gal null. Concerns have been raised that the risk of virus transmission from such pigs may be increased due to the absence of the Gal sugars. We investigated the sensitivity of porcine endogenous retrovirus (PERV) produced from Gal-null and Gal-positive pig cells to inactivation by purified NAb and human serum. PERV produced in Gal-null pig cells was resistant to inactivation by either NAb or human serum. In contrast, although Gal-positive PERV particles were sensitive to inactivation by NAb and human serum, they required markedly higher concentrations of NAb for inactivation compared to the Gal-positive cells from which they were produced. Complete inactivation of Gal-positive PERV particles was not achievable despite the use of high levels of NAb, indicating that NAb-mediated inactivation of cell-free PERV particles is an inefficient process.

Non-specific removal of antibodies in patients with idiopathic dilated cardiomyopathy: implications for xenotransplantation.

We assessed the efficiency of non-specific extracorporeal immunoadsorption (EIA), using polyclonal anti-human immunoglobulin antibodies, in depleting the serum of anti-galactosealpha1,3galactose (Gal) antibody and in decreasing serum cytotoxicity in 5 patients with idiopathic dilated cardiomyopathy. The mean concentrations of anti-Gal immunoglobulin (Ig)M and IgG before EIA were 74 microg/ml and 159 microg/ml, respectively. After EIA, these concentrations decreased by 86% and 88%, respectively. Both anti-Gal IgM and IgG returned to pre-EIA concentrations within 1 month, without rebound to greater than baseline concentrations. After EIA, mean serum cytotoxicity also decreased from 90% to 17%, with recovery by 1 month. Extracorporeal immunoadsorption proved safe in patients with heart failure and was effective in depleting anti-Gal antibody and in decreasing serum cytotoxicity to pig cells.