Genome-guided purification of high amounts of the siderophore ornibactin and detection of potentially novel burkholdine derivatives produced by Burkholderia catarinensis 89T.

AIM: The increased availability of genome sequences has enabled the development of valuable tools for the prediction and identification of bacterial natural products. Burkholderia catarinensis 89T produces siderophores and an unknown potent antifungal metabolite. The aim of this work was to identify and purify natural products of B. catarinensis 89T through a genome-guided approach. MATERIALS AND METHODS: The analysis of B. catarinensis 89T genome revealed 16 clusters putatively related to secondary metabolism and antibiotics production. Of particular note was the identification of a nonribosomal peptide synthetase (NRPS) cluster related to the production of the siderophore ornibactin, a hybrid NRPS-polyketide synthase Type 1 cluster for the production of the antifungal glycolipopeptide burkholdine, and a gene cluster encoding homoserine lactones (HSL), probably involved in the regulation of both metabolites. We were able to purify high amounts of the ornibactin derivatives D/C6 and F/C8, while also detecting the derivative B/C4 in mass spectrometry investigations. A group of metabolites with molecular masses ranging from 1188 to 1272 Da could be detected in MS experiments, which we postulate to be new burkholdine analogs produced by B. catarinensis. The comparison of B. catarinensis BGCs with other Bcc members corroborates the hypothesis that this bacterium could produce new derivatives of these metabolites. Moreover, the quorum sensing metabolites C6-HSL, C8-HSL, and 3OH-C8-HSL were observed in LC-MS/MS analysis. CONCLUSION: The new species B. catarinensis is a potential source of new bioactive secondary metabolites. Our results highlight the importance of genome-guided purification and identification of metabolites of biotechnological importance.

Nutrition outcomes and treatment toxicities in patients with head and neck cancer receiving helical intensity-modulated radiotherapy.

BACKGROUND: Helical intensity-modulated radiotherapy (H-IMRT) provides excellent limitation of dose to tissues not requiring treatment, although acute toxicity still occurs. The present study aimed to determine how treatment-related acute toxicities affect nutrition outcomes in patients with head and neck cancer. METHODS: A prospective observational study was conducted in 194 patients undergoing curative intent H-IMRT with or without other treatment modalities. Weight outcomes (kg) and acute toxicity and dysphagia data were collected during treatment using Common Toxicity Criteria for Adverse Effects (CTCAE), version 4.0. RESULTS: Significant weight loss (> 10%) was observed in 30% of high nutritional risk patients and 7% of low nutritional risk patients. Nausea, adjusted for baseline dysphagia, in high nutritional risk patients and nausea, dysphagia and pharyngeal mucositis in low nutritional risk patients were significant factors in explaining the percentage loss in baseline weight to treatment completion. CONCLUSIONS: Significant weight loss remains an issue during treatment, despite improvements in radiotherapy technology and high-level multidisciplinary care.

Comparison of Skeletal Muscle Changes at Three Vertebral Levels Following Radiotherapy in Patients With Oropharyngeal Carcinoma.

Evaluation of skeletal muscle (SM) depletion, or sarcopenia, utilizes the cross-sectional area (CSA) of computed tomography (CT) scans at the lumbar level L3. However, alternate vertebral landmarks are used in patients with head and neck cancer due to scan unavailability. Muscle changes following radiotherapy at cervical (C3) and thoracic (T2) levels were compared to L3 in patients with oropharyngeal carcinoma. Muscle density data were derived retrospectively from diagnostic PET-CT scans at C3, T2 and L3 pretreatment, and up to six months post. CSA changes were compared to L3 in scans of 33 patients (88% male, mean age 61 (SD 8.5) years). On matched pair analysis; mean L3-CSA change -12.1 cm2 (SD 9.7, 95%CI -15.5 to -8.6, and p < 0.001), T2-CSA -30.5 cm2 (SD 34.8, 95%CI -42.8 to -18.1, and p < 0.001) and C3-CSA +2.1 cm2 (SD 4.1, 95%CI 0.63 to 3.5, and p < 0.00). No difference was found in the percentage change of T2-CSA with L3-CSA (mean -2.2%, SD 10.6, 95%CI -6.0 to 1.6, and p = 0.240), however, was significantly different to C3-CSA (mean 13.2%, SD 11.6, 95%CI 9.1 to 17.3, and p < 0.001). Results suggest SM at C3 does not change proportionately and may not be a reliable representation of whole-body SM change over time.

Impact of sarcopenia and myosteatosis on survival outcomes for patients with head and neck cancer undergoing curative-intent treatment.

Malnutrition and sarcopenia are prevalent in patients with head and neck squamous cell carcinoma (HNSCC). Pre-treatment sarcopenia and adverse oncological outcomes in this population are well described. The impact of myosteatosis and post-treatment sarcopenia is less well known. Patients with HNSCC (n = 125) undergoing chemoradiotherapy, radiotherapy alone and/or surgery were assessed for sarcopenia and myosteatosis, using cross-sectional computed tomography (CT) imaging at the third lumbar (L3) vertebra, at baseline and 3 months post-treatment. Outcomes were overall survival (OS) at 12 months and 5 years post-treatment. One hundred and one participants had a CT scan evaluable at one or two time points, of which sixty-seven (66 %) participants were sarcopenic on at least one time point. Reduced muscle attenuation affected 93 % (n = 92) pre-treatment compared with 97 % (n = 90) post-treatment. Five-year OS favoured those without post-treatment sarcopenia (hazard ratio, HR 0·37, 95 % CI 0·16, 0·88, P = 0·06) and those without both post-treatment myosteatosis and sarcopenia (HR 0·33, 95 % CI 0·13, 0·83, P = 0·06). Overall, rates of myosteatosis were high at both pre- and post-treatment time points. Post-treatment sarcopenia was associated with worse 5-year OS, as was post-treatment sarcopenia in those who had myosteatosis. Post-treatment sarcopenia should be evaluated as an independent risk factor for decreased long-term survival post-treatment containing radiotherapy (RT) for HNSCC.

Improving patient and carer access to information and support through head and neck cancer treatment and survivorship using experience-based co-design.

BACKGROUND: Previous studies have highlighted the unmet nutritional and supportive care needs of patients with head and neck cancer (HNC) and their carers from diagnosis and throughout the treatment and survivorship period. The aim of this study was to bring patients, carers and healthcare professionals together to co-design a framework to improve access to nutrition information and support for patients and carers with HNC from diagnosis and throughout the treatment and survivorship period. METHODS: Using experience-based co-design (EBCD), semistructured individual interviews were conducted with patients, carers and healthcare professionals to understand their experiences in accessing information and support outside of the hospital environment. Feedback events and co-design workshops were held to prioritise areas for service improvement. RESULTS: Participants (10 patients, 7 carers and 15 healthcare professionals) highlighted the importance of having consistent information and support recommendations from the multidisciplinary team. The two key areas for improvement identified through group and workshop events were linking reputable HNC resources to a HNC portal on the hospital website and the development of a series of short podcasts and video blogs with fact sheets attached presented by members of the multidisciplinary team, patients and carers at four time points spanning pretreatment and throughout the survivorship period. CONCLUSIONS: Using EBCD has enabled the co-design of a framework for resource development with patients, carers and healthcare professionals to improve access to information and resources to support nutrition intake and supportive care needs for patients with HNC with their carers. Development and implementation of resources and evaluation of outcomes is ongoing.

A prediction model for skeletal muscle evaluation and computed tomography-defined sarcopenia diagnosis in a predominantly overweight cohort of patients with head and neck cancer.

PURPOSE: This study investigates the feasibility of computed tomography (CT)-defined sarcopenia assessment using a prediction model for estimating the cross-sectional area (CSA) of skeletal muscle (SM) in CT scans at the third lumbar vertebra (L3), using measures at the third cervical level (C3) in a predominantly overweight population with head and neck cancer (HNC). METHODS: Analysis was conducted on adult patients with newly diagnosed HNC who had a diagnostic positron emission tomography-CT scan. CSA of SM in CT images was measured at L3 and C3 in each patient, and a predictive formula developed using fivefold cross-validation and linear regression modelling. Correlation and agreement between measured CSA at L3 and predicted values were evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plot. The model's ability to identify sarcopenia was investigated using Cohen's Kappa (k). RESULTS: A total of 109 patient scans were analysed, with 64% of the cohort being overweight or obese. The prediction model demonstrated high level of correlation between measured and predicted CSA measures (ICC 0.954, r = 0.916, p < 0.001), and skeletal muscle index (SMI) (ICC 0.939, r = 0.883, p < 0.001). Bland-Altman plot showed good agreement in SMI, with mean difference (bias) = 0.22% (SD 8.65, 95% CI - 3.35 to 3.79%), limits of agreement (- 16.74 to 17.17%). The model had a sensitivity of 80.0% and specificity of 85.0%, with moderate agreement on sarcopenia diagnosis (k = 0.565, p = 0.004). CONCLUSION: This model is effective in predicting lumbar SM CSA using measures at C3, and in identifying low SM in a predominately overweight group of patients with HNC.

Thoracic skeletal muscle index is effective for CT-defined sarcopenia evaluation in patients with head and neck cancer.

PURPOSE: Computed tomography (CT)-defined sarcopenia, as a measurement of low skeletal muscle (SM), is a poor prognostic indicator in patients with head and neck cancer (HNC), independent of weight or nutritional status. We used SM measures at the second thoracic vertebra (T2) to determine T2-SM index (SMI) thresholds for sarcopenia, and investigate the impact of low T2-SMI on overall survival (OS), and weight loss during radiotherapy (RT). METHODS: Adult patients with newly diagnosed HNC with a diagnostic PET-CT or RT planning CT scan were included. SM was analysed at T2 and a model applied to predict SM at L3. T2-SMI thresholds for sarcopenia were established with predicted measures, stratified by BMI and sex. Impact of sarcopenia and low T2-SMI on OS and weight loss during RT was investigated. RESULTS: A total of 361 scans were analysed (84% males, 54% oropharynx tumours). Sarcopenia was found in 49%, demonstrating worse OS (p = 0.037). T2-SMI cutoff values were: females-74 cm2/m2 [area under the curve (AUC): 0.89 (95%CI 0.80-0.98)], males (BMI < 25)-63 cm2/m2 [AUC 0.93 (95%CI 0.89-0.96)], males (BMI ≥ 25)-88cm2/m2 [AUC 0.86 (95%CI 0.78-0.93)]. No difference in OS with T2-SMI categories. Lowest T2-SMI quartile of < 63 cm2/m2 demonstrated worse OS (p = 0.017). Weight loss during RT was higher in patients; who were not sarcopenic (6.2% vs 4.9%, p = 0.023); with higher T2-SMI (6.3% vs 4.9%, p = 0.014) and; in the highest quartiles (3.6% vs 5.7% vs 7.2%, p < 0.001). CONCLUSIONS: These T2-SMI thresholds are effective in assessing CT-defined sarcopenia in HNC. Further assessment of clinical application is warranted.

Nutritional status and post-operative complications in patients undergoing surgery for advanced pharyngeal or laryngeal cancer.

PURPOSE: Malnutrition is an important prognostic indicator of post-operative outcomes in patients undergoing surgery for head and neck cancer, however, limited studies utilize validated nutrition assessment tools to accurately assess risk. The aim of this study was to determine the relationship between nutritional status on post-operative complications and length of stay for patients undergoing either a laryngectomy, pharyngectomy or pharyngolaryngectomy for head and neck cancer. METHODS: Patients with head and neck cancer undergoing a laryngectomy, pharyngectomy or pharyngolaryngectomy at a tertiary hospital in Australia were eligible for this retrospective cohort study (n = 40). Nutritional status was assessed by the dietitian on admission using the validated Subjective Global Assessment tool. Clinical outcomes were collected via retrospective chart review and included length of stay and post-operative complications. RESULTS: Pre-operative malnutrition incidence was 40%. Malnourished patients had higher incidences of any type of complication (57% vs 44%, p = 0.013) and pressure injury (86% vs 14%, p = 0.011) compared to well-nourished patients. Well-nourished patients had a clinically important shorter median length of stay compared to malnourished patients (17.5 vs 20 days). CONCLUSION: Early identification and management of malnutrition is essential to minimize risk of post-operative complications and reduce length of stay and should be considered a key component of prehabilitation programs.

Patient and carer experience of nutrition care throughout and beyond treatment for head and neck cancer: a qualitative longitudinal study.

Nutrition care plays a critical role in optimising outcomes for patients receiving treatment for head and neck cancer (HNC), with carers playing an important role in supporting patients to maintain nutrition intake. This study explores patient and carer experience of nutrition care from diagnosis of HNC to 1 year post treatment completion to identify areas for improvement of service delivery. A longitudinal qualitative study design was used with a heterogeneous sample of 20 patients and 15 carers of patients undergoing curative intent treatment for HNC. Interviews conducted at four time points provided a total of 117 interview datasets that were analysed using reflexive thematic analysis based on Gadamerian hermeneutic inquiry. Patient and carer experiences were reflected in two primary themes: (1) the battle to maintain control and (2) navigating the road ahead. This research identifies the need to co-design strategies to improve nutrition care that is inclusive of patients and carers.

A qualitative comparison of the nutrition care experiences of carers supporting patients with head and neck cancer throughout surgery and radiation treatment and survivorship.

PURPOSE: To understand and compare the nutrition care experiences of carers supporting patients throughout surgery and radiation treatment for head and neck cancer (HNC) to inform changes to service delivery in the inpatient and outpatient setting to ensure carers needs in their supportive role throughout the treatment and survivorship period are met. METHODS: As part of a larger study, narrative interviews were completed with fourteen carers of patients diagnosed with HNC at 2 weeks, 3 months and 12 months post-treatment completion. Reflexive thematic analysis was used to interpret and understand differences in carer experiences of nutrition care between surgery and radiation treatment. RESULTS: Two main themes across each treatment modality were identified: (1) access to information and support from healthcare professionals and (2) adjustment to the physical and psychological impact of treatment. CONCLUSION: This study highlights the increasing need to ensure carers are included in the provision of nutrition information and support to patients throughout and beyond their treatment trajectory. Having structured support available to patients and carers throughout radiation treatment meant that carer needs were reduced. However, without the opportunity for structured support in the inpatient setting, many carers expressed high care needs in supporting patients in the post-surgical phase. IMPLICATIONS FOR CANCER SURVIVORS: Providing carers with access to structured support for nutrition care in the inpatient and outpatient setting can reduce their supportive care needs throughout the treatment and survivorship period.

Optimal frequency of individualised nutrition counselling in patients with head and neck cancer receiving radiotherapy: A systematic review.

BACKGROUND: Head and neck cancers (HNC) are strongly associated with malnutrition. This systematic review aimed to investigate the optimal frequency of individualised nutrition counselling (INC) pre-, peri- and post-treatment for patients with HNC. METHODS: Pubmed, EMBASE, Cinahl and Scopus were searched from inception through to April 2020 to identify randomised controlled trials (RCTs) that focused on the INC frequency for adult patients with HNC (Registration no. 178868). The outcomes assessed were nutritional status, dietary intake, weight change, treatment interruptions, unplanned hospital admissions, quality of life, complications and morbidity. Certainty of evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). RESULTS: Four RCTs were identified with five papers (n = 500 total participants). The certainty of evidence was 'high' for nutritional status and quality of life, 'moderate' for treatment interruptions and unplanned hospital admissions, and 'low' for percentage weight change, complications/morbidity and dietary intake. Compared to control groups, there were consistent improvements for nutritional status, quality of life, treatment interruptions, unplanned hospital admissions, dietary intake, percentage weight change and morbidity when weekly INC was provided peri-treatment and fortnightly INC was provided post-treatment. No statistical significance was found for treatment interruptions, dietary intake and weight change when INC was provided fortnightly peri-treatment only. There were no RCTs in the current review that offered INC pre-treatment. CONCLUSIONS: This systematic review shows beneficial effects with weekly INC peri-treatment and fortnightly INC post-treatment for patients with HNC in all outcomes studied. Future research should focus on models of care to address the optimal frequency of pre-treatment INC as well as the duration of post-treatment INC.

Exploring dyadic management of nutrition care throughout and beyond head and neck cancer treatment.

AIMS AND OBJECTIVES: To identify how patients and carers collaborate to manage nutrition care throughout and beyond head and neck cancer (HNC) treatment as a step towards identifying changes to service delivery that are inclusive of the needs of the patient-carer dyad. BACKGROUND: Research in the field of dyadic interventions in cancer care is emerging, and there has been little work exploring patient-carer dyad needs in the provision of nutrition care in HNC. DESIGN: A qualitative study design was used. METHODS: Narrative interviews were completed with 13 patients and 15 carers over a 12-month period (prior to treatment commencing, and 2 weeks, 3 months and 12 months post-treatment completion). Deductive analysis of interview transcripts was performed using directed content analysis guided by the Theory of Dyadic Illness Management (TDIM). COREQ guidelines were used. RESULTS: Seven themes across four TDIM constructs were identified: (1) understanding and adapting to physical challenges impacting nutrition intake, (2) adjusting to emotional impact of changes to eating and drinking, (3) providing practical support, (4) intrapersonal characteristics, (5) interpersonal characteristics, (6) healthcare culture and (7) managing carer burnout. CONCLUSION: This study highlights the importance of healthcare professionals recognising the patient and carer dyad as a team to enhance engagement in nutrition care and to ensure that their physical and psychological support needs across the cancer continuum are met. RELEVANCE TO CLINICAL PRACTICE: It is important that healthcare professionals understand information and support needs and preferences within patient-carer dyads prior to HNC treatment commencing and adapt care and interventions based on their changing needs throughout and beyond the treatment period.

"There's a lot of talent in the room but it's only really the medical talent that gets heard": a qualitative exploration of multidisciplinary clinicians' perspectives of optimal nutrition care of patients with head and neck cancer.

BACKGROUND: The high prevalence of malnutrition in patients with head and neck cancer (HNC) negatively impacts outcomes. The best-available evidence has been published in clinical nutrition guidelines; however, translation into practice has lagged. AIM: This project aimed to explore multidisciplinary team (MDT) clinicians' perspectives regarding barriers and enablers to best-practice nutrition care in order to inform the design of a new model of care. METHOD: Qualitative interviews were conducted with clinicians who were purposively sampled from a major HNC tertiary referral centre in Sydney, Australia. To elicit information regarding barriers and facilitators to change, a semi-structured interview schedule was developed, interviews were transcribed verbatim and analyzed employing an inductive thematic approach. The Consolidated Framework for Implementation Research (CFIR) was used to guide data analysis and interpretation of key themes identified. RESULTS: Nineteen participants (11 supportive care and eight medical clinicians) representing allied health, medical, and nursing disciplines participated. Five key themes were identified: (1) acknowledgement of dietetics expertise and access to resources to deliver nutrition care; (2) proactive versus reactive nutrition care; (3) integrated and coordinated care-"The One Stop Shop"; (4) MDT favours the medical model; and (5) leadership-within disciplines, within the MDT. CONCLUSIONS: MDT clinicians expressed similar views regarding delivering optimal nutrition care to this high nutritional risk patient group. However, perspectives differed at times between medical and supportive care clinicians, attributable to perceptions that current service structure favours the medical model. In order to design and deliver an evidence-based model of care, specific strategies will be required to ensure: early and ongoing access to expert nutrition care; nutrition care processes are proactive; integrated and coordinated care; and leadership, both intra- and inter-disciplinary. This novel exploration of MDT clinicians' views provides supporting evidence that multi-component implementation strategies comprising individual, team and system-level approaches will be essential to leverage sustainable change.

Altered dietary salt intake for people with chronic kidney disease.

BACKGROUND: Evidence indicates that reducing dietary salt may reduce the incidence of heart disease and delay decline in kidney function in people with chronic kidney disease (CKD). This is an update of a review first published in 2015. OBJECTIVES: To evaluate the benefits and harms of altering dietary salt for adults with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 6 October 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials comparing two or more levels of salt intake in adults with any stage of CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility, conducted risk of bias evaluation and evaluated confidence in the evidence using GRADE. Results were summarised using random effects models as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included 21 studies (1197 randomised participants), 12 in the earlier stages of CKD (779 randomised participants), seven in dialysis (363 randomised participants) and two in post-transplant (55 randomised participants). Selection bias was low in seven studies, high in one and unclear in 13. Performance and detection biases were low in four studies, high in two, and unclear in 15. Attrition and reporting biases were low in 10 studies, high in three and unclear in eight. Because duration of the included studies was too short (1 to 36 weeks) to test the effect of salt restriction on endpoints such as death, cardiovascular events or CKD progression, changes in salt intake on blood pressure and other secondary risk factors were examined. Reducing salt by mean -73.51 mmol/day (95% CI -92.76 to -54.27), equivalent to 4.2 g or 1690 mg sodium/day, reduced systolic/diastolic blood pressure by -6.91/-3.91 mm Hg (95% CI -8.82 to -4.99/-4.80 to -3.02; 19 studies, 1405 participants; high certainty evidence). Albuminuria was reduced by 36% (95% CI 26 to 44) in six studies, five of which were carried out in people in the earlier stages of CKD (MD -0.44, 95% CI -0.58 to -0.30; 501 participants; high certainty evidence). The evidence is very uncertain about the effect of lower salt intake on weight, as the weight change observed (-1.32 kg, 95% CI -1.94 to -0.70; 12 studies, 759 participants) may have been due to fluid volume, lean tissue, or body fat. Lower salt intake may reduce extracellular fluid volume in the earlier stages of CKD (-0.87 L, 95% CI -1.17 to -0.58; 3 studies; 187 participants; low certainty evidence). The evidence is very uncertain about the effect of lower salt intake on reduction in antihypertensive dose (RR 2.45, 95% CI 0.98 to 6.08; 8 studies; 754 participants). Lower salt intake may lead to  symptomatic hypotension (RR 6.70, 95% CI 2.40 to 18.69; 6 studies; 678 participants; moderate certainty evidence). Data were sparse for other types of adverse events. AUTHORS' CONCLUSIONS: We found high certainty evidence that salt reduction reduced blood pressure in people with CKD, and albuminuria in people with earlier stage CKD in the short-term. If such reductions could be maintained long-term, this effect may translate to clinically significant reductions in CKD progression and cardiovascular events. Research into the long-term effects of sodium-restricted diet for people with CKD is warranted.

Patient and carer experience of nutrition care throughout treatment for head and neck cancer: a systematic qualitative review and thematic synthesis.

Nutrition care plays a critical role in the provision of best practice care to head and neck cancer (HNC) patients, with carers playing an important role in supporting patients to maintain nutrition intake. This qualitative systematic review investigated patient and carer experience of nutrition care throughout and beyond HNC treatment. Five databases were systematically searched for qualitative studies reporting on patient and carer experience of nutrition care throughout HNC. Twenty-five studies including 435 patients and 46 carers were identified, revealing three themes: information and support in the healthcare setting, enteral feeding challenges and management, and life outside hospital. Findings highlight the importance of providing individualised person-centred nutrition care to patients with HNC and their carers. Further qualitative research is needed to inform healthcare professionals about the needs of patients and carers to provide appropriate support throughout the treatment trajectory across and between different treatment modalities.

"Completely and utterly flummoxed and out of my depth": patient and caregiver experiences during and after treatment for head and neck cancer-a qualitative evaluation of barriers and facilitators to best-practice nutrition care.

BACKGROUND: Malnutrition is prevalent in patients with head and neck cancer (HNC), impacting on outcomes. Despite publication of best-practice nutrition care clinical guidelines, evidence-practice gaps persist. AIM: This project aimed to understand the perspectives of patients and their caregivers about nutritional care and how their unmet supportive care needs can be better addressed in designing a new model of care (MOC). The results will contribute to documenting the barriers and enablers to implementing best practice nutrition care for patients with HNC. METHOD: Qualitative interviews were conducted with patients who had completed radiotherapy with or without (+/-) other treatment modality (surgery and/or systematic therapy) of curative intent for HNC. Patients were purposively sampled from a major tertiary referral centre in Sydney, Australia. Patients' primary caregivers were also invited to participate if both parties consented. A semi-structured interview schedule was developed to elicit information about barriers and facilitators to change and inform development of the new MOC. Interviews were transcribed verbatim then analysed using an inductive thematic approach. This study was one component of a mixed methods design to explore the barriers and facilitators to best-practice nutrition care in a head and neck oncology unit. RESULTS: Eleven participants (seven patients, four caregivers) took part in the interviews. Four key themes were identified with branching themes within each: (1) being ill-prepared for the impact of treatment, even when advised; (2) navigating complex systems to meet significant care needs; (3) depleted by overwhelming and prolonged suffering; and (4) information lost in translation. CONCLUSIONS: This study highlights the unique and complex care needs of people with HNC and those caring for them. To design and successfully deliver a patient-centred MOC, specific strategies will be required to address: early and ongoing access to expert supportive care clinicians; integrated and coordinated care; individual information, education and support needs and; and education of MDT staff in accurate and consistent messaging, ensuring nutrition care is a collective responsibility. Nutrition care did not appear to be viewed separately to overall care from the patient perspective as the importance of nutrition ultimately became viewed as vital treatment.

Effect of early and intensive nutrition care, delivered via telephone or mobile application, on quality of life in people with upper gastrointestinal cancer: study protocol of a randomised controlled trial.

BACKGROUND: A major challenge for those living with cancers of the upper gastrointestinal tract (oesophagus, stomach and pancreas), is the impact of the disease and treatment on nutritional status and quality of life. People with cancer and malnutrition have a greater risk of morbidity and mortality. Nutrition intervention is recommended to commence immediately in those who are malnourished or at risk of malnutrition. Novel cost-effective approaches that can deliver early, pre-hospital nutrition intervention before usual hospital dietetic service is commenced are needed. Linking clinicians and patients via mobile health (mHealth) and wireless technologies is a contemporary solution not yet tested for delivery of nutrition therapy to people with cancer. The aim of this study is to commence nutrition intervention earlier than usual care and evaluate the effects of using the telephone or mHealth for intervention delivery. It is hypothesised that participants allocated to receive the early and intensive pre-hospital dietetic service will have more quality-adjusted life years lived compared with control participants. This study will also demonstrate the feasibility and effectiveness of mHealth for the nutrition management of patients at home undergoing cancer treatment. METHODS: This study is a prospective three-group randomised controlled trial, with a concurrent economic evaluation. The 18 week intervention is provided in addition to usual care and is delivered by two different modes, via telephone (group 1) or via mHealth (group 2), The control group receives usual care alone (group 3). The intervention is an individually tailored, symptom-directed nutritional behavioural management program led by a dietitian. Participants will have at least fortnightly reviews. The primary outcome is quality adjusted life years lived and secondary outcomes include markers of nutritional status. Outcomes will be measured at three, six and 12 months follow up. DISCUSSION: The findings will provide evidence of a strategy to implement early and intensive nutrition intervention outside the hospital setting that can favourably impact on quality of life and nutritional status. This patient-centred approach is relevant to current health service provision and challenges the current reactive delivery model of care. TRIAL REGISTRATION: 27th January 2017 Australian and New Zealand Clinical Trial Registry ( ACTRN12617000152325 ).

Head and neck cancer patient experience of a new dietitian-delivered health behaviour intervention: 'you know you have to eat to survive'.

PURPOSE: The aim of this study was to explore head and neck cancer (HNC) patient experiences of a novel dietitian delivered health behaviour intervention. METHODS: This study is a qualitative study which employed semi-structured individual interviews using open and axial coding and then final selective coding to organise the data. Patients with HNC who had participated in a dietitian delivered health behaviour intervention to reduce malnutrition were invited to discuss their experience of this intervention. Individual interviews were conducted, transcribed and analysed using grounded theory. RESULTS: Nine patients participated in the interviews. Four dimensions were identified in the initial coding process: 'information', which described patients' desire for tailored advice during their treatment; 'challenges of treatment experience', which described the difficulties related to treatment side effects; 'key messages: importance of eating and maintaining weight', which covered perceived integral messages delivered to patients by dietitians; and 'dietitian's approach' describing patient experiences of empathic and compassionate dietitians. Two overarching themes resulted from examining the connections and relationships between these dimensions: 'survival', a connection between eating and living; and 'support', describing the valued working partnership between dietitian and patient. CONCLUSIONS: Dimensions and themes overlapped with the qualitative literature on HNC patient experience of treatment. However, some themes, such as the empowerment of a message linking eating to survival, appeared unique to this study. Patients found this message to be delivered in a supportive manner that motivated change.

Randomised controlled trial of early prophylactic feeding vs standard care in patients with head and neck cancer.

BACKGROUND: Weight loss remains significant in patients with head and neck cancer, despite prophylactic gastrostomy and intensive dietary counseling. The aim of this study was to improve outcomes utilising an early nutrition intervention. METHODS: Patients with head and neck cancer at a tertiary hospital in Australia referred for prophylactic gastrostomy prior to curative intent treatment were eligible for this single centre randomised controlled trial. Exclusions included severe malnutrition or dysphagia. Patients were assigned following computer-generated randomisation sequence with allocation concealment to either intervention or standard care. The intervention group commenced supplementary tube feeding immediately following tube placement. Primary outcome measure was percentage weight loss at three months post treatment. RESULTS: Recruitment completed June 2015 with 70 patients randomised to standard care (66 complete cases) and 61 to intervention (56 complete cases). Following intention-to-treat analysis, linear regression found no effect of the intervention on weight loss (10.9±6.6% standard care vs 10.8±5.6% intervention, P=0.930) and this remained non-significant on multivariable analysis (P=0.624). No other differences were found for quality of life or clinical outcomes. No serious adverse events were reported. CONCLUSIONS: The early intervention did not improve outcomes, but poor adherence to nutrition recommendations impacted on potential outcomes.

dRNA-seq transcriptional profiling of the FK506 biosynthetic gene cluster in Streptomyces tsukubaensis NRRL18488 and general analysis of the transcriptome.

FK506 (tacrolimus) is a valuable immunosuppressant produced by several Streptomyces strains. In the genome of the wild type producer Streptomyces tsukubaensis NRRL18488, FK506 biosynthesis is encoded by a gene cluster that spans 83.5 (kb). A whole transcriptome differential shotgun sequencing (dRNA-seq) of S. tsukubaensis was performed to analyze transcription at 2 different time points; before and during active FK506 production. In total, 8,914 transcription start sites were identified in either condition, which enabled precise determination of the 5'-UTR length of the corresponding transcripts as well as the identification of 2 consensus sequence motifs in the promoter regions. The transcription start sites of all gene operons within the FK506 cluster were identified, including 3 examples of leaderless RNA transcripts. These data provide detailed insight into the transcription of the FK506 biosynthetic gene cluster to support future regulatory studies, genetic manipulation, and industrial production.