Outcomes for recurrent oral cavity squamous cell carcinoma.

OBJECTIVES: We sought to determine overall survival (OS), prognostic factors, cost, and functional outcomes after surgery for locally recurrent oral cavity squamous cell carcinoma (OCSCC). MATERIALS AND METHODS: We retrospectively reviewed 399 cases of locally recurrent OCSCC from 1997 to 2011, of which 259 patients were treated with salvage surgery. Survival and prognostic factors were evaluated using univariable and multivariable Cox regression, the Kaplan-Meier method, and the log-rank test. RESULTS: The 5-year OS for patients undergoing surgical salvage, nonsurgical therapy, or supportive care was 44.2%, 1.5%, and 0%, respectively. For patients who underwent surgical salvage, 133 (51%) patients experienced a second recurrence at a median of 17 months. Factors associated with OS included disease-free interval ≤ 6 months (P =.0001), recurrent stage III-IV disease (P <.0001), and prior radiation (P =.0001). Patients with both advanced stage and prior radiation had a 23% 5-year OS, compared with 70% for those with neither risk (P <.001). Functionally, 85% of patients had > 80% speech intelligibility and 81% were able to eat by mouth following salvage surgery. Of the patients who required tracheostomy, 78% were decannulated. The adjusted median hospital and professional charges for patients were $129,696 (range $9,238-$956,818). CONCLUSIONS: Patients with recurrent OCSCC who underwent salvage surgery have favorable functional outcomes with half of alive at 5 years but poorer OS for advanced disease, disease-free interval ≤ 6 months, and prior radiation. Additionally, treatment is associated with high cost, and about half of patients ultimately develop another recurrence.

Clinical recovery of 5 dogs from amatoxin mushroom poisoning using an adapted Santa Cruz protocol for people.

OBJECTIVE: To describe the clinical course, treatment, and outcome of 5 dogs following ingestion of toxic Amanita spp. mushrooms containing amatoxins using an adapted version of the Santa Cruz protocol developed for people. CASE SERIES SUMMARY: Five dogs were presented with clinical signs compatible with amanitin toxicity with witnessed ingestion noted in 3 of 5 dogs. Clinical findings included acute onset vomiting and diarrhea, lethargy, and hepatopathy including signs of fulminant hepatic failure (increased liver enzyme activities, hyperbilirubinemia, prolonged clotting times, and hypoglycemia were noted among these cases). Urine toxicological screening confirmed the presence of Amanita toxins in 4 cases with expert mycologist speciation in the fifth. Core interventions included percutaneous biliary drainage, use of octreotide, and early nil per os orders. All dogs survived to discharge with this treatment strategy. NEW OR UNIQUE INFORMATION PROVIDED: This case series describes the use of a modified version of the Santa Cruz protocol to address amatoxin-induced fulminant hepatic failure in dogs. The protocol was safe, well tolerated, and all patients made a full clinical recovery.

Peer Mentors for People with Advanced Cancer: Lessons Learnt from Recruiting and Training Peer Mentors for a Feasibility Randomized Controlled Trial.

Peer mentors may offer distinctive forms of support to people with advanced cancer. Whilst peer mentor programmes are known, little is understood about recruiting and training peer mentors to support those with advanced cancer. The purpose of this study is to determine the feasibility of recruiting and training peer mentors for a novel peer mentor intervention to promote well-being in people with advanced cancer. Feasibility study testing proactive introduction to a trained peer mentor for 12 weeks in the context of a randomized controlled two-arm trial and nested qualitative process evaluation was used. Peer mentors have/had cancer, recruited via an open call. Two-day training included a new bespoke module on coping with cancer. Descriptive recruitment and training data were captured, supplemented by qualitative interviews, analysed thematically. Forty-eight people expressed interest, mostly female (69%), with breast cancer (32%), and recruited via social media (49%). Twelve people completed training, with attrition often due to availability or mentors' own health; many had advanced cancer themselves. They wanted to 'give something back', but also formed supportive bonds with fellow mentors. It is feasible to recruit and train people with lived experience of cancer to be peer mentors, but those with particular characteristics may predominate. Broad social media based recruitment may have merit in widening the pool of potential peer mentors.

Peer support to maintain psychological wellbeing in people with advanced cancer: findings from a feasibility study for a randomised controlled trial.

BACKGROUND: Advanced cancer affects people's lives, often causing stress, anxiety and depression. Peer mentor interventions are used to address psychosocial concerns, but their outcomes and effect are not known. Our objective was to determine the feasibility of delivering and investigating a novel peer mentor intervention to promote and maintain psychological wellbeing in people with advanced cancer. METHODS: A mixed methods design incorporating a two-armed controlled trial (random allocation ratio 1:1) of a proactive peer mentor intervention plus usual care, vs. usual care alone, and a qualitative process evaluation. Peer mentors were recruited, trained, and matched with people with advanced cancer. Quantitative data assessed quality of life, coping styles, depression, social support and use of healthcare and other supports. Qualitative interviews probed experiences of the study and intervention. RESULTS: Peer mentor training and numbers (n = 12) met feasibility targets. Patient participants (n = 12, from 181 eligible who received an information pack) were not recruited to feasibility targets. Those who entered the study demonstrated that intervention delivery and data collection were feasible. Outcome data must be treated with extreme caution due to small numbers, but indicate that the intervention may have a positive effect on quality of life. CONCLUSIONS: Peer mentor interventions are worthy of further study and researchers can learn from these feasibility data in planning participant recruitment and data collection strategies. Pragmatic trials, where the effectiveness of an intervention is tested in real-world routine practice, may be most appropriate. Peer mentor interventions may have merit in enabling survivors with advanced cancer cope with their disease. TRIAL REGISTRATION: The trial was prospectively registered 13.6.2016: ISRCTN10276684 .

Peer support for people with advanced cancer: a systematically constructed scoping review of quantitative and qualitative evidence.

PURPOSE OF REVIEW: The number of people living with advanced cancer is increasing, and appropriate support to this population is essential. Peer support is increasingly advocated as a component of care, but little is known about how to provide this in the context of advanced cancer. This review describes the experience and impact of different forms of peer support for people with advanced cancer. RECENT FINDINGS: Data from 22 articles were reviewed, primarily descriptive studies. They describe three forms of peer support (one-to-one, group, and online), reaching primarily those who are women, middle-aged, and well educated. Only two studies focused on support to people with advanced cancer, but those with advanced cancer were frequent users of all forms of peer support. Benefits of peer support were described, but no data were presented to allow a determination of the best form of support for people with advanced cancer. SUMMARY: Practitioners can be assured that peer support is likely to be beneficial and provide care that complements that of clinicians. However, there is a need for a comprehensive programme of high-quality evaluative research of peer support for people with advanced cancer.

Suicide Prevention for School Communities: An Educational Initiative for Student Safety.

A knowledge gap exists in school communities regarding suicide prevention and means reduction education. The article highlights two core interrelated topics: school nurse engagement in dialogue with students' families and the implementation of an innovative, community-based suicide prevention educational program at a suburban public school district. The authors provide an overview of the public health problem of suicide for students, current student challenges, role of the school nurse in suicide prevention, and a key gap in current school nursing practice. At the request of the school counselors and principal, an innovative suicide prevention educational program was initiated as a community-based project at a large suburban public school district in Texas. The two overarching goals for this community-based collaboration are the following: school nurses will engage in frank, productive conversations with students' parents and families about suicidality concerns and increase the school community's knowledge about suicide prevention. This school community knowledge includes effective risk mitigation and means reduction strategies to better manage suicidality in students. Ultimately, this ongoing family and school community collaboration aims to prevent student deaths by suicide.

A revised model for coping with advanced cancer. Mapping concepts from a longitudinal qualitative study of patients and carers coping with advanced cancer onto Folkman and Greer's theoretical model of appraisal and coping.

OBJECTIVE: To explore whether the Folkman and Greer theoretical model of appraisal and coping reflects the processes used by people living with advanced cancer. METHODS: Interview data from a longitudinal qualitative study with people with advanced (stage 3 or 4) cancer (n = 26) were mapped onto the concepts of the Folkman and Greer theoretical model. Qualitative interviews conducted in home settings, 4-12 weeks apart (n = 45) examined coping strategies, why people thought they were effective, and in what circumstances. Interviews were coded and analysed using techniques of constant comparison. RESULTS: Mapping coping strategies clearly onto the problem- or emotion-focused elements of the model proved problematic. Fluctuating symptoms, deterioration over time, and uncertain timescales in advanced cancer produce multiple events simultaneously or in quick succession. This demands not only coping with a single event but also frequent repositioning, often to an earlier point in the coping process. In addition, there is substantial ongoing potential for some degree of distress rather than purely "positive emotion" as the final stage in the process is death with several points of permanent loss of capability in the interim. CONCLUSIONS: The Folkman and Greer theoretical model is helpful in deconstructing the discrete "problem-focused" or "emotion-focused" coping mechanisms participants describe, but its formulation as a linear process with a single, positive, outcome is insufficiently flexible to capture the evolution of coping for people with advanced cancer.

Coping Well with Advanced Cancer: A Serial Qualitative Interview Study with Patients and Family Carers.

OBJECTIVES: To understand successful strategies used by people to cope well when living with advanced cancer; to explore how professionals can support effective coping strategies; to understand how to support development of effective coping strategies for patients and family carers. DESIGN: Qualitative serial (4-12 week intervals) interview study with people with advanced cancer and their informal carers followed by focus groups. The iterative design had a novel focus on positive coping strategies. Interview analysis focused on patients and carers as individuals and pairs, exploring multiple dimensions of their coping experiences. Focus group analysis explored strategies for intervention development. PARTICIPANTS: 26 people with advanced (stage 3-4) breast, prostate, lung or colorectal cancer, or in receipt of palliative care, and 24 paired nominated informal/family carers. SETTING: Participants recruited through outpatient clinics at two tertiary cancer centres in Merseyside and Manchester, UK, between June 2012 and July 2013. RESULTS: 45 patient and 41 carer interviews were conducted plus 4 focus groups (16 participants). People with advanced cancer and their informal/family carers develop coping strategies which enable effective management of psychological wellbeing. People draw from pre-diagnosis coping strategies, but these develop through responding to the experience of living with advanced cancer. Strategies include being realistic, indulgence, support, and learning from others, which enabled participants to regain a sense of wellbeing after emotional challenge. Learning from peers emerged as particularly important in promoting psychological wellbeing through the development of effective 'everyday', non-clinical coping strategies. CONCLUSIONS: Our findings challenge current models of providing psychological support for those with advanced cancer which focus on professional intervention. It is important to recognise, enable and support peoples' own resources and coping strategies. Peer support may have potential, and could be a patient-centred, cost effective way of managing the needs of a growing population of those living with advanced cancer.

Competitive antagonists facilitate the recovery from desensitization of α1ß2γ2 GABAA receptors expressed in Xenopus oocytes.

AIM: The continuous presence of an agonist drives its receptor into a refractory state, termed desensitization. In this study, we tested the hypothesis that a competitive antagonist, SR95531, could facilitate the recovery of α1ß2γ2 GABAA receptor from functional desensitization. METHODS: α1ß2γ2 GABAA receptors were expressed in Xenopus oocytes. GABA-evoked currents were recorded using two-electrode voltage-clamp technique. Drugs were applied through perfusion. RESULTS: Long application of GABA (100 µmol/L) evoked a large peak current followed by a small amplitude steady-state current (desensitization). Co-application of SR95531 during the desensitization caused a larger rebound of GABA current after removal of SR95531. Furthermore, application of SR95531 after removal of GABA increased the rate of receptor recovery from desensitization, and the recovery time constant was decreased from 59±3.2 s to 33±1.6 s. SR95531-facilitated receptor recovery from desensitization was dependent on the perfusion duration of SR95531. It was also dependent on the concentration of SR95531, and the curve fitting with Hill equation revealed two potency components, which were similar to the two potency components in inhibition of the steady-state current by SR95531. Bicuculline caused similar facilitation of desensitization recovery. CONCLUSION: SR95531 facilitates α1ß2γ2 GABAA receptor recovery from desensitization, possibly through two mechanisms: binding to the desensitized receptor and converting it to the non-desensitized state, and binding to the resting state receptor and preventing re-desensitization.

School-based blood drive: successful nurse collaboration with parents, students, and the community.

The nurses at an independent Pre-K through 12 educational institution in Houston, Texas (The Kinkaid School), expanded the blood drive program to include innovative collaboration with high school student leaders, parents, and school faculty. Methods implemented in this endeavor included technology utilization, science education, and an enhanced parent workforce. By focusing on community involvement and an altruistic reason for donating, the Kinkaid school nurses helped their community break school donation records 2 years in a row.

Environmental requirements related to patient care and the team working to ensure compliance.

Healthcare providers are often surprised that regulations promulgated by the US Environmental Protection Agency (EPA) apply to patient care settings. Many find it strange that processes meant to heal have the potential to harm human health and the environment, and are, therefore, regulated by federal and state environmental agencies. The importance of compliance is emphasized by the fact that both the EPA and individual state agencies have the authority to impose civil and criminal penalties if they discover violations. The Joint Commission considers compliance important enough to include it as an element of performance in the Environment of Care standard.

Protocol for a longitudinal qualitative interview study: maintaining psychological well-being in advanced cancer--what can we learn from patients' and carers' own coping strategies?

INTRODUCTION: People with advanced cancer and their carers experience stress and uncertainty which affects the quality of life and physical and mental health. This study aims to understand how patients and carers recover or maintain psychological well-being by exploring the strategies employed to self-manage stress and uncertainty. METHODS AND ANALYSIS: A longitudinal qualitative interview approach with 30 patients with advanced cancer and 30 associated family or informal carers allows the exploration of contexts, mechanisms and outcomes at an individual level. Two interviews, 4-12 weeks apart, will not only enable the exploration of individuals' evolving coping strategies in response to changing contexts but also how patients' and carers' strategies inter-relate. Patient and Carer focus groups will then consider how the findings may be used in developing an intervention. Recruiting through two major tertiary cancer centres in the North West and using deliberately broad and inclusive criteria will enable the sample to capture demographic and experiential breadth. ETHICS AND DISSEMINATION: The research team will draw on their considerable experience to ensure that the study is sensitive to a patient and carer group, which may be considered vulnerable but still values being able to contribute its views. Public and patient involvement (PPI) is integral to the design and is evidenced by: a research advisory group incorporating patient and carers, prestudy consultations with the PPI group at one of the study sites and a user as the named applicant. The study team will use multiple methods to disseminate the findings to clinical, policy and academic audiences. A key element will be engaging health professionals in patient and carer ideas for promoting self-management of psychological well-being. The study has ethical approval from the North West Research Ethics Committee and the appropriate NHS governance clearance. REGISTRATION: National Institute for Health Research (NIHR) Clinical Studies Portfolio, UK Clinical Research Network (UKCRN) Study number 11725.

Molecular and functional characterization of the human platelet Na(+) /Ca(2+) exchangers.

BACKGROUND AND PURPOSE The Na(+) /Ca(2+) exchanger is a bi-directional transporter that plays an important role in maintaining the concentration of cytosolic Ca(2+) ([Ca(2+) ](i) ) of quiescent platelets and increasing it during activation with some, but not all, agonists. There are two classes of Na(+) /Ca(2+) exchangers: K(+) -independent Na(+) /Ca(2+) exchanger (NCX) and K(+) -dependent Na(+) /Ca(2+) exchanger (NCKX). Platelets have previously been shown to express NCKX1. However, initial studies from our laboratory suggest that NCX may also play a role in platelet activation. The objective of this study was to determine if the human platelet expresses functional NCXs. EXPERIMENTAL APPROACH RT-PCR, DNA sequencing and Western blot analysis were utilized to characterize the human platelet Na(+) /Ca(2+) exchangers. Their function during quiescence and collagen-induced activation was determined by measuring [Ca(2+) ](i) with calcium-green/fura-red in response to: changes in the Na(+) and K(+) gradient, NCX pharmacological inhibitors (CBDMB, KB-R7943 and SEA0400) and antibodies specific to extracellular epitopes of the exchangers. KEY RESULTS Human platelets express NCX1.3, NCX3.2 and NCX3.4. The NCXs operate in the Ca(2+) efflux mode in resting platelets and also during their activation with thrombin but not collagen. Collagen-induced increase in [Ca(2+) ](i) was reduced with the pharmacological inhibitors of NCX (CBDMB, KB-R7943 or SEA0400), anti-NCX1 and anti-NCX3. In contrast, anti-NCKX1 enhanced the collagen-induced increase in [Ca(2+) ](i) . CONCLUSIONS AND IMPLICATIONS Human platelets express K(+) -independent Na(+) /Ca(2+) exchangers NCX1.3, NCX3.2 and NCX3.4. During collagen activation, NCX1 and NCX3 transiently reverse to promote Ca(2+) influx, whereas NCKX1 continues to operate in the Ca(2+) efflux mode to reduce [Ca(2+) ](i) .

Lysozyme, a mediator of sepsis, impairs the cardiac neural adrenergic response by nonendothelial release of NO and inhibitory G protein signaling.

We previously showed that lysozyme (Lzm-S), derived from leukocytes, caused myocardial depression in canine sepsis by binding to the endocardial endothelium to release nitric oxide (NO). NO then diffuses to adjacent myocytes to activate the cGMP pathway. In a canine right ventricular trabecular (RVT) preparation, Lzm-S also decreased the inotropic response to field stimulation (FSR) during which the sympathetic and parasympathetic nerves were simulated to measure the adrenergic response. In the present study, we determined whether the pathway by which Lzm-S decreased FSR was different from the pathway by which Lzm-S reduced steady-state (SS) contraction. Furthermore, we determined whether the decrease in FSR was due to a decrease in sympathetic stimulation or enhanced parasympathetic signaling. In the RVT preparation, we found that the inhibitory effect of Lzm-S on FSR was prevented by NO synthase (NOS) inhibitors. A cGMP inhibitor also blocked the depressant activity of Lzm-S. However, in contrast to the Lzm-S-induced decline in SS contraction, chemical removal of the endocardial endothelium by Triton X-100 to eliminate endothelial NO release did not prevent the decrease in FSR. An inhibitory G protein was involved in the effect of Lzm-S, since FSR could be restored by treatment with pertussis toxin. Atropine prevented the Lzm-S-induced decline in FSR, whereas beta(1)- and beta(2)-adrenoceptor function was not impaired by Lzm-S. These results indicate that the Lzm-S-induced decrease in FSR results from a nonendothelial release of NO. NO then acts through inhibitory G protein to enhance parasympathetic signaling.

Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity.

A common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. Such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of anti-vector immunity. Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in preclinical studies but will probably be limited by the high prevalence of pre-existing anti-Ad5 immunity in human populations, particularly in the developing world. Here we show that rAd5 vectors can be engineered to circumvent anti-Ad5 immunity. We constructed novel chimaeric rAd5 vectors in which the seven short hypervariable regions (HVRs) on the surface of the Ad5 hexon protein were replaced with the corresponding HVRs from the rare adenovirus serotype Ad48. These HVR-chimaeric rAd5 vectors were produced at high titres and were stable through serial passages in vitro. HVR-chimaeric rAd5 vectors expressing simian immunodeficiency virus Gag proved comparably immunogenic to parental rAd5 vectors in naive mice and rhesus monkeys. In the presence of high levels of pre-existing anti-Ad5 immunity, the immunogenicity of HVR-chimaeric rAd5 vectors was not detectably suppressed, whereas the immunogenicity of parental rAd5 vectors was abrogated. These data demonstrate that functionally relevant Ad5-specific neutralizing antibodies are focused on epitopes located within the hexon HVRs. Moreover, these studies show that recombinant viral vectors can be engineered to circumvent pre-existing anti-vector immunity by removing key neutralizing epitopes on the surface of viral capsid proteins. Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy.

Lysozyme binding to endocardial endothelium mediates myocardial depression by the nitric oxide guanosine 3',5' monophosphate pathway in sepsis.

Inflammatory mediators have been implicated as a cause of reversible myocardial depression in septic shock. We previously reported that the release of lysozyme-c (Lmz-S) from leukocytes from the spleen or other organs contributes to myocardial dysfunction in Escherichia coli septic shock in dogs by binding to a cardiac membrane glycoprotein. However, the mechanism by which Lzm-S causes this depression has not been elucidated. In the present study, we tested the hypothesis that the binding of Lzm-S to a membrane glycoprotein causes myocardial depression by the formation of nitric oxide (NO). NO generation then activates soluble guanylyl cyclase and increases cyclic guanosine monophosphate (cGMP), which in turn triggers contractile impairment via activation of cGMP-dependent protein kinase (PKG). We examined these possibilities in a right ventricular trabecular preparation in which isometric contraction was used to measure cardiac contractility. We found that Lzm-S's depressant effect could be prevented by the non-specific NO synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA). A guanylyl cyclase inhibitor (ODQ) and a PKG inhibitor (Rp-8-Br-cGMP) also attenuated Lzm-S's depressant effect as did chemical denudation of the endocardial endothelium (EE) with Triton X-100 (0.5%). In EE tissue, we further showed that Lzm-S caused NO release with use of 4,5 diaminofluorescein, a fluorescent dye that binds to NO. The present study shows that the binding of Lzm-S to EE generates NO, and that NO then activates the myocardial guanosine 3',5' monophosphate pathway leading to cardiac depression in sepsis.

Effects of social work intervention on nonemergent pediatric emergency department utilization.

The purpose of this study was to determine whether social work intervention would reduce nonemergent visits to the emergency department and increase scheduled pediatric visits. A high-risk repeater group of 104 pediatric patients with three or more emergency department visits was randomly selected to receive social work intervention. Control and intervention groups were compared for inappropriate emergency department utilization and scheduled primary care visits. Pre- and postintervention emergency department visits were significantly reduced in the intervention group compared with the group that received no intervention and with prior utilization. Scheduled visits declined in the control group but increased by 26 percent in the intervention group.

Mechanism of collagen activation in human platelets.

The mechanism of collagen-induced human platelet activation was examined using Ca2+, Na+, and the pH-sensitive fluorescent dyes calcium green/fura red, sodium-binding benzofuran isophthalate, and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Administration of a moderate dose of collagen (10 microg/ml) to human platelets resulted in an increase in [Ca2+](i) and platelet aggregation. The majority of this increase in [Ca2+](i) resulted from the influx of calcium from the extracellular milieu via the Na+/Ca2+ exchanger (NCX) functioning in the reverse mode and was reduced in a dose-dependent manner by the NCX inhibitors 5-(4-chlorobenzyl)-2',4'-dimethylbenzamil (KD(50) = 4.7 +/- 1.1 microm) and KB-R7943 (KD(50) = 35.1 +/- 4.8 microm). Collagen-induced platelet aggregation was dependent on an increase in [Ca2+](i) and could be inhibited by chelation of intra- and extracellular calcium through the administration of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM) and EGTA, respectively, or via the administration of BAPTA-AM to platelets suspended in no-Na+/HEPES buffer. Collagen induced an increase in [Ca2+](i) (23.2 +/- 7.6 mm) via the actions of thromboxane A(2) and, to a lesser extent, of the Na+/H+ exchanger. This study demonstrates that the collagen-induced increase in [Ca2+](i) is dependent on the concentration of Na+ in the extracellular milieu, indicating that the collagen-induced increase in [Ca2+](i) causes the reversal of the NCX, ultimately resulting in an increase in [Ca2+](i) and platelet aggregation.