Trend analysis and prediction of seasonal changes in milk composition from a pasture-based dairy research herd.

The composition of seasonal pasture-produced milk is influenced by stage of lactation, animal genetics, and nutrition, which affects milk nutritional profile and processing characteristics. The objective was to study the effect of lactation stage (early, mid, and late lactation) and diet on milk composition in an Irish spring calving dairy research herd from 2012 to 2020 using principal component and predictive analytics. Crude protein, casein, fat, and solids increased from 2012 to 2020, whereas lactose concentration peaked in 2017, then decreased. Based on seasonal data from 2013 to 2016, forecasting models were successfully created to predict milk composition for 2017 to 2020. The diet of cows in this study is dependent upon grass growth rates across the milk production season, which in turn, are influenced by weather patterns, whereby extreme weather conditions (rainfall and temperature) were correlated with decreasing grass growth and increasing nonprotein nitrogen levels in milk. The study demonstrates a significant change in milk composition since 2012 and highlights the effect that seasonal changes such as weather and grass growth have on milk composition of pasture-based systems. The potential to forecast milk composition at different stages of lactation benefits processers by facilitating the optimization of in-process and supply logistics of dairy products.

What is the impact of dexamethasone on postoperative pain in adults undergoing general anaesthesia for elective abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: Previous meta-analysis of heterogeneous surgical cohorts demonstrated reduction in postoperative pain with perioperative intravenous dexamethasone, but none have addressed adults undergoing elective abdominal surgery. The aim of this study was to determine the impact of intravenous perioperative dexamethasone on postoperative pain in adults undergoing elective abdominal surgery under general anaesthesia. METHODS: This review was prospectively registered on the international prospective register of systematic reviews (CRD42020176202). Electronic databases Medical Analysis and Retrieval System Online (MEDLINE), Exerpta Medica Database (EMBASE), (CINAHL) Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and trial registries were searched to January 28 2021 for randomised controlled trials, comparing dexamethasone to placebo or alternative antiemetic, that reported pain. The primary outcome was pain score, and secondary outcomes were time to first analgesia, opioid requirements and time to post-anaesthesia care unit (PACU) discharge. RESULTS: Fifty-two studies (5768 participants) were included in the meta-analysis. Pain scores ≤ 4 hour (h) were reduced in patients who received dexamethasone at rest (mean difference (MD), - 0.54, 95% confidence interval (CI) - 0.72 to - 0.35, I2 = 81%) and on movement (MD - 0.42, 95% CI - 0.62 to - 0.22, I2 = 35). In the dexamethasone group, 4-24 h pain scores were less at rest (MD - 0.31, 95% CI - 0.47 to - 0.14, I2 = 96) and on movement (MD - 0.26, 95% CI - 0.39 to - 0.13, I2 = 29) and pain scores ≥ 24 h were reduced at rest (MD - 0.38, 95% CI - 0.52 to - 0.24, I2 = 88) and on movement (MD - 0.38, 95% CI - 0.65 to - 0.11, I2 = 71). Time to first analgesia (minutes) was increased (MD 22.92, 95% CI 11.09 to 34.75, I2 = 98), opioid requirements (mg oral morphine) decreased (MD - 6.66, 95% CI - 9.38 to - 3.93, I2 = 88) and no difference in time to PACU discharge (MD - 3.82, 95% CI - 10.87 to 3.23, I2 = 59%). CONCLUSIONS: Patients receiving dexamethasone had reduced pain scores, postoperative opioid requirements and longer time to first analgesia. Dexamethasone is an effective analgesic adjunct for patients undergoing abdominal surgery.

Whispering Tuberculosis.

Presentation We describe a case of reactivation of latent pulmonary tuberculosis (TB) invading the larynx and causing dysphonia. Diagnosis A previously healthy 30-year old woman was found to have bilateral pulmonary TB 5-months after being thoroughly investigated for hoarseness. Initial chest x-ray (CXR) and CT-neck were normal. Vocal cord biopsies were negative for granulomata. Treatment The patient was commenced on standard four drug Anti-TB treatment (ATT) and completed a one-year course. Unfortunately, the development of a laryngeal web caused persistent dysphonia. Discussion Patients with laryngeal TB are more likely to present to ENT surgeons, because of the initial symptom of hoarseness. Multiple tests must be completed before out-ruling TB. HRCT or sputum culture is recommended, as TB may not be evident on initial CXR. A collaborative approach between Respiratory and ENT teams is required. Prompt diagnosis is essential. Speech therapy input will be important in our patient's recovery.

Applications of nonthermal plasma technology on safety and quality of dried food ingredients.

Cold plasma technology is an efficient, environmental-friendly, economic and noninvasive technology; and in recent years these advantages placed this novel technology at the centre of diverse studies for food industry applications. Dried food ingredients including spices, herbs, powders and seeds are an important part of the human diet; and the growing demands of consumers for higher quality and safe food products have led to increased research into alternative decontamination methods. Numerous studies have investigated the effect of nonthermal plasma on dried food ingredients for food safety and quality purposes. This review provides critical review on potential of cold plasma for disinfection of dried food surfaces (spices, herbs and seeds), improvement of functional and rheological properties of dried ingredients (powders, proteins and starches). The review further highlights the benefits of plasma treatment for enhancement of seeds performance and germination yield which could be applied in agricultural sector in near future. Different studies applying plasma technology for control of pathogens and spoilage micro-organisms and modification of food quality and germination of dried food products followed by benefits and current challenges are presented. However, more systemic research needs to be addressed for successful adoption of this technology in food industry.

Oxygen Therapy in Ireland: A Nationwide Review of Delivery, Monitoring and Cost Implications

Aims Our aim was to establish which hospitals in Ireland are running oxygen clinics and to compare oxygen prescription in hospitals to a guideline standard. Long term oxygen therapy is known to be of benefit to a specific cohort of patients but is not without risk. Methods We sent an online questionnaire and followed up by phone to representatives in Irish hospitals in which domiciliary oxygen is prescribed. We obtained responses from 32 hospitals. Results Twelve hospitals (38%) had a dedicated oxygen assessment clinic while twenty (62%) did not. Centres without oxygen clinics generally prescribed oxygen following an in-patient stay 18/23 centres (78%) and were unable to provide follow up for patients on oxygen in 6/23 centres (26%). Centres with oxygen clinics generally met criteria for initial assessment and oxygen prescription, however titration of oxygen and general follow up did not meet guideline recommendations. Conclusion Due to a lack of dedicated oxygen assessment and review services, many Irish patients are not optimally treated with domiciliary oxygen.

Endogenous circulating testosterone and sex hormone-binding globulin levels and measures of myocardial structure and function: the Framingham Heart Study.

BACKGROUND: The relation between endogenous testosterone concentrations and myocardial mass and function remains incompletely understood. OBJECTIVES: To determine the cross-sectional association between endogenous hormone levels with cardiac magnetic resonance measures of myocardial mass, structure, and function in community-dwelling men across a wide age range. METHODS: A total of 720 men from the Framingham Heart Study Offspring Cohort (age range 37-82, mean = 59.6 years) who underwent cardiac magnetic resonance imaging and had hormone levels measured. Total testosterone (measured using liquid chromatography-tandem mass spectrometry), sex hormone-binding globulin (measured using an immunofluorometric assay), and calculated free testosterone levels were assessed in male participants of the Framingham Heart Study Offspring Cohort at examination 7. Cardiac magnetic resonance imaging was performed between examinations 7 and 8 (2002-2006). RESULTS: Age-adjusted linear regression models showed statistically significant association between total testosterone levels and left ventricular mass (p = 0.009), left ventricular mass index (p = 0.006), cardiac output (p = 0.001), and main pulmonary artery diameter (p = 0.008); the association between total testosterone and these cardiac magnetic resonance measures was weak and was not significant after adjustment for established risk factors-age, body mass index, diabetes, and hypertension. Furthermore, calculated free testosterone level was not significantly associated with any measure of myocardial mass or function. Sex hormone-binding globulin level was significantly associated with left ventricular mass (p = 0.002), left ventricular mass index (p = 0.004), cardiac output (p = 0.003), left ventricular ejection fraction (p = 0.039), and main pulmonary artery diameter (p = 0.042) in age-adjusted models; these associations were also rendered non-significant after adjusting for cardiovascular risk factors. CONCLUSIONS: Neither testosterone nor sex hormone-binding globulin levels in men are associated significantly with myocardial mass and function independent of established cardiovascular risk factors.

Development of a Core Outcome Set for studies evaluating the effects of anaesthesia on perioperative morbidity and mortality following hip fracture surgery.

BACKGROUND: Perioperative studies of patients following hip fracture have large heterogeneity within their reported outcomes. This study aimed to develop a core outcome set for use in perioperative studies comparing the types of anaesthesia for hip fracture surgery. METHODS: The consensus process consisted of a systematic review of the literature, three rounds of a Delphi survey, two consensus webinars, and face-to-face patient meetings. RESULTS: The Delphi participants represented nine stakeholder groups. The numbers of participants completing Rounds 1-3 were 242, 186, and 169, respectively. Seventeen outcomes that met the predefined consensus criteria were considered at two consensus meetings. A final set of 10 core outcomes was agreed: mortality, time from injury to surgery, acute coronary syndrome, hypotension, acute kidney injury, delirium, pneumonia, orthogeriatric input, being out of bed at day 1, and pain. CONCLUSIONS: We generated a consensus-based set of core outcomes recommended for use in all perioperative trials evaluating the effects of anaesthesia for hip fracture surgery. An important next step is developing consensus-based consistency on how they should be measured. CLINICAL TRIAL REGISTRATION: http://www.comet-initiative.org/studies/details/757.

Azithromycin Fails to Prevent Accelerated Airway Obliteration in T-bet-/- Mouse Lung Allograft Recipients.

BACKGROUND: Cellular and molecular mechanisms of acute and chronic lung allograft rejection have yet to be clearly defined, and obliterative bronchiolitis (OB) remains the primary limitation to survival in lung transplant recipients (LTRs). We have previously shown that T-bet-deficient recipients of full major histocompatibility complex (MHC)-mismatched, orthotopic left lung transplants develop accelerated obliterative airway disease (OAD) in the setting of acute cellular rejection characterized by robust alloimmune CD8+ interleukin (IL)-17 and interferon (IFN)-γ responses that are attenuated with neutralization of IL-17. Azithromycin has been shown to be beneficial in some LTRs with bronchiolitis obliterans syndrome/OB. Here, we evaluated the effects of azithromycin on rejection pathology and T-cell effector responses in T-bet-/- recipients of lung transplants. METHODS: Orthotopic left lung transplantation was performed in BALB/c → B6 wild type or BALB/c → B6 T-bet-/- strain combinations as previously described. Mice treated with azithromycin received 10 mg/kg or 50 mg/kg subcutaneously daily. Lung allograft histopathology was analyzed at day 10 or day 21 post-transplantation, and neutrophil staining for quantification was performed using anti-myeloperoxidase. Allograft mononuclear cells were isolated at day 10 for T-cell effector cytokine response assessment using flow cytometry. RESULTS: We show that while azithromycin significantly decreases lung allograft neutrophilia and CXCL1 levels and attenuates allospecific CD8+ IL-17 responses early post-transplantation, OAD persists in T-bet-deficient mice. CONCLUSIONS: Our results indicate that lung allograft neutrophilia is not essential for the development of OAD in this model and suggest allospecific T-cell responses that remain despite marked attenuation of CD8+ IL-17 are sufficient for obliterative airway inflammation and fibrosis.

Early-life regional and temporal variation in filaggrin-derived natural moisturizing factor, filaggrin-processing enzyme activity, corneocyte phenotypes and plasmin activity: implications for atopic dermatitis.

BACKGROUND: Filaggrin is central to the pathogenesis of atopic dermatitis (AD). The cheeks are a common initiation site of infantile AD. Regional and temporal expression of levels of filaggrin degradation products [natural moisturizing factors (NMFs)], activities of filaggrin-processing enzymes [bleomycin hydrolase (BH) and calpain-1 (C-1)] and plasmin, and corneocyte envelope (CE) maturity in early life are largely unknown. OBJECTIVES: We conducted a cross-sectional, observational study investigating regional and age-dependent variations in NMF levels, activity of proteases and CE maturity in stratum corneum (SC) from infants to determine whether these factors could explain the observed predilection sites for AD in early life. METHODS: We measured NMF using a tape-stripping method at seven sites in the SC of 129 children (aged < 12 months to 72 months) and in three sites in 56 neonates and infants (< 48 h to 3 months). In 37 of these neonates and infants, corneocyte size, maturity, BH, C-1 and plasmin activities were determined. RESULTS: NMF levels are low at birth and increase with age. Cheek SC, compared with elbow flexure and nasal tip, has the lowest NMF in the first year of life and is the slowest to reach stable levels. Cheek corneocytes remain immature. Plasmin, BH and C-1 activities are all elevated by 1 month of age in exposed cheek skin, but not in elbow skin. CONCLUSIONS: Regional and temporal differences in NMF levels, CE maturity and protease activities may explain the predilection for AD to affect the cheeks initially and are supportive of this site as key for allergen priming in early childhood. These observations will help design early intervention and treatment strategies for AD.

Perioperative outcomes in the context of mode of anaesthesia for patients undergoing hip fracture surgery: systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses on the anaesthetic management of patients undergoing surgery for hip fracture have focused on randomized trials. Furthermore, heterogeneity in outcome reporting across the studies has made it difficult to inform best practice guidelines for patient care. METHODS: This systematic review examined how perioperative outcomes were reported and defined in the context of comparing modes of anaesthesia for hip fracture surgery. Outcomes were included from randomised and non-randomised studies published between January 2000 and July 2017. Meta-analyses were performed for regional versus general anaesthesia, with sensitivity analyses performed for spinal versus general anaesthesia. RESULTS: By including data from 15 large observational studies in this meta-analysis, we have increased the number of patients for whom outcomes were assessed from approximately 3000 to 202 000. There was no significant difference in 30-day mortality (OR 1.02; 95% CI 0.96, 1.07, I2 31%; n=200 616), prevalence of pneumonia (OR 1.07; 95% CI 0.94, 1.23, I2 34%; n=65 011), acute myocardial infarction (OR 0.96; 95% CI 0.88, 1.04, I2 0%, n=64 904), delirium (OR 1.07; 95% CI 0.72, 1.58, I2 93%, n=19 923), or renal failure (OR 0.94; 95% CI 0.54, 1.64, I2 0%, n=27 873) for regional compared with general anaesthesia [corrected]. There was a small statistically significant difference for length of stay (standardized mean difference -0.03; 95% CI -0.05, -0.02; I2 0%; n=78 711) favouring regional anaesthesia, which is unlikely to be clinically significant. Sensitivity analyses for the same outcomes examining spinal only vs general anaesthesia showed minor statistical significance for length of stay favouring spinal. We also present data highlighting the scale of the inconsistencies in reported outcomes across 32 studies, making evaluation in a standardized manner very difficult. As an example, mortality was reported in nine different ways throughout the studies. CONCLUSIONS: We highlight the need for agreement on outcome definitions and for a minimum core outcome set to be measured and reported in hip fracture studies. This would strengthen the evidence-based approach to delivering optimal care.

Ileocolonic neuroendocrine tumours identified in the English bowel cancer screening programme.

AIM: Ileocolonic neuroendocrine tumours (NETs) are diagnosed as part of bowel cancer screening programmes (BCSPs). The aim of this study was to identify and characterize NETs diagnosed within the English BCSP, a double-screen programme that uses guaic faecal occult blood test (gFOBT) screening and colonoscopy, by interrogating the national colorectal screening database and validating the findings with individual BCSP centres. METHOD: The Exeter database was interrogated by running queries to identify participants with coded NETs (from the start of the programme in July 2006 - 1 December 2014). A written proforma was sent to the responsible BCSP clinician for validation and characterization. RESULTS: During this period, 13 061 716 participants were adequately screened using gFOBTs, and 259 765 participants had definitively abnormal results. There were 146 unique participants with NET-related codes from 216 707 BCSP colonoscopies. The diagnosis rates per 100 000 colonoscopies were 29 rectal, 18 colonic and 11 ileal NETs. The majority of rectal NETs had Grade 1 (80%) and Stage T1 (85.1%) disease. Over half of ileal NETs (53.6%) in this study had invasive disease, with 85.2% having nodal and 36.1% having metastastatic disease. CONCLUSION: The current study highlights the rate of colorectal NETs diagnosed in the English BCSP. These data highlight a higher-than-anticipated incidence, and the potential additional benefit of BCSPs in identifying occult NETs.

Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.

Using Participatory Learning & Action (PLA) research techniques for inter-stakeholder dialogue in primary healthcare: an analysis of stakeholders' experiences.

PLAIN ENGLISH SUMMARY: It is important for health care workers to know the needs and expectations of their patients. Therefore, service users have to be involved in research. To achieve a meaningful dialogue between service users, healthcare workers and researchers, participatory methods are needed. This paper describes how the application of a specific participatory methodology, Participatory Learning and Action (PLA) can lead to such a meaningful dialogue. In PLA all stakeholders are regarded as equal partners and collaborators in research.During 2011-2015, a European project called RESTORE used PLA in Austria, Greece, Ireland, The Netherlands and the UK to investigate how communication between primary health care workers and their migrant patients could be improved.Seventy eight migrants, interpreters, doctors, nurses and other key stakeholders (see Table 2) participated in 62 PLA sessions. These dialogues (involving discussions, activities, PLA techniques and evaluations) were generally 2-3 h long and were recorded and analysed by the researchers.Participants reported many positive experiences about their dialogues with other stakeholders. There was a positive, trusting atmosphere in which all stakeholders could express their views despite differences in social power. This made for better understanding within and across stakeholder groups. For instance a doctor changed her view on the use of interpreters after a migrant explained why this was important. Negative experiences were rare: some doctors and healthcare workers thought the PLA sessions took a lot of time; and despite the good dialogue, there was disappointment that very few migrants used the new interpreting service. ABSTRACT: Background In order to be effective, primary healthcare must understand the health needs, values and expectations of the population it serves. Recent research has shown that the involvement of service users and other stakeholders and gathering information on their perspectives can contribute positively to many aspects of primary healthcare. Participatory methodologies have the potential to support engagement and dialogue between stakeholders from academic, migrant community and health service settings. This paper focuses on a specific participatory research methodology, Participatory Learning and Action (PLA) in which all stakeholders are regarded as equal partners and collaborators in research.Our research question for this paper was: "Does the application of PLA lead to meaningful engagement of all stakeholders, and if so, what elements contribute to a positive and productive inter-stakeholder dialogue?". Methods We explored the use of PLA in RESTORE, a European FP7-funded project, during 2011-2015 in 5 countries: Austria, Greece, Ireland, the Netherlands and the UK. The objective of RESTORE was to investigate and support the implementation of guidelines and training initiatives (G/TIs) to enhance communication in cross-cultural primary care consultations with migrants.Seventy eight stakeholders (migrants, interpreters, doctors, nurses and others - see Table 2) participated in a total of 62 PLA sessions (discussions, activities, evaluations) of approximately 2-3 h' duration across the five sites. During the fieldwork, qualitative data were generated about stakeholders' experiences of engagement in this dialogue, by means of various methods including participatory evaluations, researchers' fieldwork reports and researcher interviews. These were analysed following the principles of thematic analysis. Results Stakeholders involved in PLA inter-stakeholder dialogues reported a wide range of positive experiences of engagement, and very few negative experiences. A positive atmosphere during early research sessions helped to create a sense of safety and trust. This enabled stakeholders from very different backgrounds, with different social status and power, to offer their perspectives in a way that led to enhanced learning in the group - they learned with and from each other. This fostered shifts in understanding - for example, a doctor changed her view on interpreted consultations because of the input of the migrant service-users. Conclusion PLA successfully promoted stakeholder involvement in meaningful and productive inter-stakeholder dialogues. This makes it an attractive approach to enhance the further development of health research partnerships to advance primary healthcare.

Evaluation of ensemble Monte Carlo variable selection for identification of metabolite markers on NMR data.

The aim of this study was to investigate the potential of the recently developed ensemble Monte Carlo Variable Selection (EMCVS) method to identify the relevant portions of high resolution 1H NMR spectra as a metabolite fingerprinting tool and compare to a widely used method (Variable importance on projection (VIP)) and recently proposed variable selected methods i.e. selectivity ratio (SR) and significance multivariate correlation (sMC). As case studies two quantitative publicly available datasets: wine samples, urine samples of rats, and an experiment on mushroom (Agaricus bisporus) were examined. EMCVS outperformed the three other variable selection methods in most cases, selecting fewer chemical shifts and leading to improved classification of mushrooms and prediction of onion by-products intake and wine components. These fewer chemical shift regions facilitate the interpretation of the NMR spectra, fingerprinting and identification of metabolite markers.

Implementing guidelines and training initiatives to improve cross-cultural communication in primary care consultations: a qualitative participatory European study.

BACKGROUND: Cross-cultural communication in primary care is often difficult, leading to unsatisfactory, substandard care. Supportive evidence-based guidelines and training initiatives (G/TIs) exist to enhance cross cultural communication but their use in practice is sporadic. The objective of this paper is to elucidate how migrants and other stakeholders can adapt, introduce and evaluate such G/TIs in daily clinical practice. METHODS: We undertook linked qualitative case studies to implement G/TIs focused on enhancing cross cultural communication in primary care, in five European countries. We combined Normalisation Process Theory (NPT) as an analytical framework, with Participatory Learning and Action (PLA) as the research method to engage migrants, primary healthcare providers and other stakeholders. Across all five sites, 66 stakeholders participated in 62 PLA-style focus groups over a 19 month period, and took part in activities to adapt, introduce, and evaluate the G/TIs. Data, including transcripts of group meetings and researchers' fieldwork reports, were coded and thematically analysed by each team using NPT. RESULTS: In all settings, engaging migrants and other stakeholders was challenging but feasible. Stakeholders made significant adaptations to the G/TIs to fit their local context, for example, changing the focus of a G/TI from palliative care to mental health; or altering the target audience from General Practitioners (GPs) to the wider multidisciplinary team. They also progressed plans to deliver them in routine practice, for example liaising with GP practices regarding timing and location of training sessions and to evaluate their impact. All stakeholders reported benefits of the implemented G/TIs in daily practice. Training primary care teams (clinicians and administrators) resulted in a more tolerant attitude and more effective communication, with better focus on migrants' needs. Implementation of interpreter services was difficult mainly because of financial and other resource constraints. However, when used, migrants were more likely to trust the GP's diagnoses and GPs reported a clearer understanding of migrants' symptoms. CONCLUSIONS: Migrants, primary care providers and other key stakeholders can work effectively together to adapt and implement G/TIs to improve communication in cross-cultural consultations, and enhance understanding and trust between GPs and migrant patients.

The Effect of Aerosol Saline on Laboratory-Induced Dyspnea.

PURPOSE: In the 'placebo arm' of a recent study, we found that aerosol saline (sham treatment) produced substantial relief of laboratory-induced dyspnea (Breathing discomfort-BD) in nearly half the subjects. The sham intervention included a physiological change, and instructions to subjects could have produced expectation of dyspnea relief. In the present study, we attempted to discover whether the response to sham aerosol was driven by behavioral or physiological aspects of the intervention. METHODS: Dyspnea (air hunger) was evoked by constraining tidal volume during graded hypercapnia. We measured [Formula: see text] versus BD relationship before and after aerosol saline. To minimize subjects' expectations of dyspnea relief, participants were clearly instructed that we would only deliver saline aerosol. In Protocol 1, we delivered aerosol saline with a ventilator (mimicking our prior study); in Protocol 2, we delivered aerosol without a ventilator. RESULTS: Administration of aerosol saline had little effect on BD in this group of subjects with one exception: one subject experienced appreciable reduction in BD in Protocol 1. This treatment effect was less in Protocol 2. The two most likely explanations are (a) that procedures surrounding ventilator administration of aerosol produced a psychological placebo treatment effect even though the subject knew a drug was not given; (b) there were behavioral changes in breathing undetected by our measurements of respiratory flow and volume that altered the subjects comfort. CONCLUSION: When the expectation of treatment effect is minimized, a significant reduction in dyspnea in response to saline placebo is uncommon but not impossible.

Validation of the EORTC QLQ-BIL21 questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder.

BACKGROUND: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice. METHODS: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed. RESULTS: Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach's α-coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change. CONCLUSIONS: The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder.