Temperature monitoring of nonanaesthetised patients in a cardiac catheterisation laboratory

Aim and objectives To identify the prevalence that temperature reduced by more than 1°C from pre to post-procedure in a sample of non-anaesthetised patients undergoing procedures in a cardiac catheterisation laboratory. Background Advances in medical technology are minimising the invasiveness of diagnostic tests and treatments for disease, which is correspondingly increasing the number of medical procedures performed without sedation or anaesthesia. Procedural areas in which medical procedures are performed without anaesthesia are typically kept at a cool temperature for staff comfort. As such, there is a need to inform nursing practices in regard to the thermal management of non-anaesthetised patients undergoing procedures in surgical or procedural environments. Design Single-site observational study Methods Patients were included if they had undergone an elective procedure without sedation or anaesthesia in a cardiac catheterisation laboratory. Ambient room temperature was maintained between 18°C and 20°C. Passive warming with heated cotton blankets was applied. Nurses measured body temperature and thermal comfort before and after 342 procedures. Results Mean change in temperature was -0.08°C (Standard deviation 0.43). The reduction in temperature was more than 1°C after 11 procedures (3.2%). One patient whose temperature had reduced more than 1°C after their procedure reported thermal discomfort. A total of 12 patients were observed to be shivering post-procedure (3.6%). No demographic or clinical characteristics were associated with reduction in temperature of more than 1°C from pre to post-procedure. Conclusions Significant reduction in body temperature was rare in our sample of non-anaesthetised patients. Relevance to clinical practice Similar results would likely be found in other procedural contexts during procedures conducted in settings with comparable room temperatures where passive warming can also be applied with limited skin exposure.

IMPOSE (IMProving Outcomes after Sepsis)—the effect of a multidisciplinary follow-up service on health-related quality of life in patients postsepsis syndromes—a double-blinded randomised controlled trial: protocol

Introduction Patients post sepsis syndromes have a poor quality of life and a high rate of recurring illness or mortality. Follow-up clinics have been instituted for patients postgeneral intensive care but evidence is sparse, and there has been no clinic specifically for survivors of sepsis. The aim of this trial is to investigate if targeted screening and appropriate intervention to these patients can result in an improved quality of life (Short Form 36 health survey (SF36V.2)), decreased mortality in the first 12 months, decreased readmission to hospital and/or decreased use of health resources. Methods and analysis 204 patients postsepsis syndromes will be randomised to one of the two groups. The intervention group will attend an outpatient clinic two monthly for 6 months and receive screening and targeted intervention. The usual care group will remain under the care of their physician. To analyse the results, a baseline comparison will be carried out between each group. Generalised estimating equations will compare the SF36 domain scores between groups and across time points. Mortality will be compared between groups using a Cox proportional hazards (time until death) analysis. Time to first readmission will be compared between groups by a survival analysis. Healthcare costs will be compared between groups using a generalised linear model. Economic (health resource) evaluation will be a within-trial incremental cost utility analysis with a societal perspective. Ethics and dissemination Ethical approval has been granted by the Royal Brisbane and Women’s Hospital Human Research Ethics Committee (HREC; HREC/13/QRBW/17), The University of Queensland HREC (2013000543), Griffith University (RHS/08/14/HREC) and the Australian Government Department of Health (26/2013). The results of this study will be submitted to peer-reviewed intensive care journals and presented at national and international intensive care and/or rehabilitation conferences.

Impact of chemotherapy on cancer-related fatigue and cytokines in 1312 patients: A systematic review of quantitative studies

Purpose of review: Cancer-related fatigue (CRF) is the most common psychosomatic distress experienced by cancer patients before, during and after chemotherapy. Its impact on functional status and Health Related Quality of Life is a great concern among patients, healthcare professionals and researchers. The primary objective of this systematic review is to determine whether the different chemotherapies affect the association of CRF with individual pro- and anti-inflammatory cytokines. The PRISMA statement guideline has been followed to systematically search and screen article from PubMed and Embase. Recent findings: This review has examined 14 studies which included a total of 1312 patients. These studies assayed 20 different kinds of cytokines. The cytokines interleukin-6, interleukin-1RA, TGF-[beta] and sTNF-R2 were associated with CRF in patients receiving anthracycline-based chemotherapy. However, only interleukin-13 was identified in the taxane-based chemotherapy. Similarly, different sets of cytokines were linked with CRF in patients with chemotherapy regimens containing platinum, cyclophosphamides, topotecan or bleomycin. Summary: This review has identified that cytokines are differentially linked with CRF according to the various types of chemotherapy regimens.

Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection

Extrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes.

The prevalence and correlates of childhood trauma in patients with early psychosis

Objective: To describe the prevalence and demographic, clinical and functional correlates of childhood trauma in patients attending early psychosis clinics. Method: Participants were recruited from outpatients attending four early psychosis services. Exposure to childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Psychopathology was measured using the Positive and Negative Syndrome Scale and the Depression, Anxiety and Stress Scale. Social and vocational functioning and substance use were also assessed. Results: Over three-quarters of the 100 patients reported exposure to any childhood trauma. Emotional, physical and sexual abuse were reported by 54%, 23% and 28% of patients, respectively, while 49% and 42% of patients reported emotional and physical neglect, respectively. Female participants were significantly more likely to be exposed to emotional and sexual abuse. Exposure to childhood trauma was correlated with positive psychotic symptoms and higher levels of depressive, anxiety and stress symptoms; however, it had no impact on social or vocational functioning or recent substance use. Conclusion: Exposure to childhood trauma was common in patients with early psychosis, and associated with increased symptomatology. Existing recommendations that standard clinical assessment of patients with early psychosis should include inquiry into exposure to childhood trauma are supported.

Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial

Background The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and gefitinib in this setting. Methods This multicentre, international, open-label, exploratory, randomised controlled phase 2B trial (LUX-Lung 7) was done at 64 centres in 13 countries. Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation (exon 19 deletion or Leu858Arg) were randomly assigned (1:1) to receive afatinib (40 mg per day) or gefitinib (250 mg per day) until disease progression, or beyond if deemed beneficial by the investigator. Randomisation, stratified by EGFR mutation type and status of brain metastases, was done centrally using a validated number generating system implemented via an interactive voice or web-based response system with a block size of four. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. Coprimary endpoints were progression-free survival by independent central review, time-to-treatment failure, and overall survival. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01466660. Findings Between Dec 13, 2011, and Aug 8, 2013, 319 patients were randomly assigned (160 to afatinib and 159 to gefitinib). Median follow-up was 27·3 months (IQR 15·3–33·9). Progression-free survival (median 11·0 months [95% CI 10·6–12·9] with afatinib vs 10·9 months [9·1–11·5] with gefitinib; hazard ratio [HR] 0·73 [95% CI 0·57–0·95], p=0·017) and time-to-treatment failure (median 13·7 months [95% CI 11·9–15·0] with afatinib vs 11·5 months [10·1–13·1] with gefitinib; HR 0·73 [95% CI 0·58–0·92], p=0·0073) were significantly longer with afatinib than with gefitinib. Overall survival data are not mature. The most common treatment-related grade 3 or 4 adverse events were diarrhoea (20 [13%] of 160 patients given afatinib vs two [1%] of 159 given gefitinib) and rash or acne (15 [9%] patients given afatinib vs five [3%] of those given gefitinib) and liver enzyme elevations (no patients given afatinib vs 14 [9%] of those given gefitinib). Serious treatment-related adverse events occurred in 17 (11%) patients in the afatinib group and seven (4%) in the gefitinib group. Ten (6%) patients in each group discontinued treatment due to drug-related adverse events. 15 (9%) fatal adverse events occurred in the afatinib group and ten (6%) in the gefitinib group. All but one of these deaths were considered unrelated to treatment; one patient in the gefitinib group died from drug-related hepatic and renal failure. Interpretation Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population.

First-Line afatinib versus chemotherapy in patients with non–small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases

Introduction Metastatic spread to the brain is common in patients with non–small cell lung cancer (NSCLC), but these patients are generally excluded from prospective clinical trials. The studies, phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations (LUX-Lung 3) and a randomized, open-label, phase III study of BIBW 2992 versus chemotherapy as first-line treatment for patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation (LUX-Lung 6) investigated first-line afatinib versus platinum-based chemotherapy in epidermal growth factor receptor gene (EGFR) mutation-positive patients with NSCLC and included patients with brain metastases; prespecified subgroup analyses are assessed in this article. Methods For both LUX-Lung 3 and LUX-Lung 6, prespecified subgroup analyses of progression-free survival (PFS), overall survival, and objective response rate were undertaken in patients with asymptomatic brain metastases at baseline (n = 35 and n = 46, respectively). Post hoc analyses of clinical outcomes was undertaken in the combined data set (n = 81). Results In both studies, there was a trend toward improved PFS with afatinib versus chemotherapy in patients with brain metastases (LUX-Lung 3: 11.1 versus 5.4 months, hazard ratio [HR] = 0.54, p = 0.1378; LUX-Lung 6: 8.2 versus 4.7 months, HR = 0.47, p = 0.1060). The magnitude of PFS improvement with afatinib was similar to that observed in patients without brain metastases. In combined analysis, PFS was significantly improved with afatinib versus with chemotherapy in patients with brain metastases (8.2 versus 5.4 months; HR, 0.50; p = 0.0297). Afatinib significantly improved the objective response rate versus chemotherapy in patients with brain metastases. Safety findings were consistent with previous reports. Conclusions These findings lend support to the clinical activity of afatinib in EGFR mutation–positive patients with NSCLC and asymptomatic brain metastases.

Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small-cell lung cancer (NSCLC) patients: Results of an open-label, randomized, controlled phase II study (CERTO)

Background: This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200. Results: There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvβ3 and αvβ5 expression was neither a predictive nor a prognostic indicator. Conclusions: The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment.

Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): Pooled subset analyses from two randomized trials

Background: The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases. Methods: The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib. Results: One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0–18.2] with dacomitinib and 9.6 months (95% CI 7.4–12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458–1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6–41.5) with dacomitinib versus 23.2 months (95% CI 16.0–31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431–1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib. Conclusions: Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721). Clinical trials number: ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).

Mutational analysis of the insulin‑like growth factor 1 receptor tyrosine kinase domain in non-small cell lung cancer patients

The insulin‑like growth factor 1 receptor (IGF1R) pathway plays an important role in the pathogenesis of non‑small cell lung cancer (NSCLC) and also provides a mechanism of resistance to targeted therapies. IGF1R is therefore an ideal therapeutic target and several inhibitors have entered clinical trials. However, thus far the response to these inhibitors has been poor, highlighting the importance of predictive biomarkers to identify patient cohorts who will benefit from these targeted agents. It is well‑documented that mutations and/or deletions in the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain predict sensitivity of NSCLC patients to EGFR TK inhibitors. Single‑nucleotide polymorphisms (SNPs) in the IGF pathway have been associated with disease, including breast and prostate cancer. The aim of the present study was to elucidate whether the IGF1R TK domain harbours SNPs, somatic mutations or deletions in NSCLC patients and correlates the mutation status to patient clinicopathological data and prognosis. Initially 100 NSCLC patients were screened for mutations/deletions in the IGF1R TK domain (exons 16‑21) by sequencing analysis. Following the identification of SNP rs2229765, a further 98 NSCLC patients and 866 healthy disease‑free control patients were genotyped using an SNP assay. The synonymous SNP (rs2229765) was the only aberrant base change identified in the IGF1R TK domain of 100 NSCLC patients initially analysed. SNP rs2229765 was detected in exon 16 and was found to have no significant association between IGF1R expression and survival. The GA genotype was identified in 53.5 and 49.4% of NSCLC patients and control individuals, respectively. No significant difference was found in the genotype (P=0.5487) or allele (P=0.9082) frequencies between the case and control group. The present findings indicate that in contrast to the EGFR TK domain, the IGF1R TK domain is not frequently mutated in NSCLC patients. The synonymous SNP (rs2229765) had no significant association between IGF1R expression and survival in the cohort of NSCLC patients.

Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer

Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application. In this investigation, two-dimensional difference gel electrophoresis and mass spectrometry were initially used to analyse conditioned media from a panel of lung cancer and normal bronchial epithelial cell lines. Significant proteins were identified with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), pyruvate kinase M2 isoform (PKM2), Hsc-70 interacting protein and lactate dehydrogenase A (LDHA) selected for analysis in serum from healthy individuals and lung cancer patients. hnRNPA2B1, PKM2 and LDHA were found to be statistically significant in all comparisons. Tissue analysis and knockdown of hnRNPA2B1 using siRNA subsequently demonstrated both the overexpression and potential role for this molecule in lung tumorigenesis. The data presented highlights a number of in vitro derived candidate biomarkers subsequently verified in patient samples and also provides some insight into their roles in the complex intracellular mechanisms associated with tumour progression.

Editorial: Are adolescent and young adult cancer patients affected by ‘chemobrain’?: A call for evidence

An adolescent and young adult (AYA) cancer patient is defined as an individual of 15 to 39 years of age at the time of initial cancer diagnosis.1,2 The number of AYA cancer survivors has dramatically increased over the past decades due to availability of novel therapeutics, with the 5-year overall survival rate among adolescents aged 15 to 19 years old exceeds 80% for most cancers.3 AYA cancer survivors, however, often experience a myriad of treatment-related chronic and late toxicities that can lead to functional impairment at great economic, emotional and social cost.4 As the cure rates of AYA cancers continue to improve and survivors live longer, post-treatment health issues in these survivors are becoming increasingly relevant, and more in-depth research is needed in this group of patients...

Associations between dehydration, cognitive impairment and frailty in older hospitalized patients: An exploratory study

An exploratory study was undertaken to assess the prevalence of dehydration in older patients (aged ≥60 years) with and without cognitive impairment (CI) admitted to hospital and to examine associations between dehydration, CI and frailty. Forty-four patients participated and dehydration was assessed within 24 hours of admission and at day 4 or at discharge, whichever occurred first (study exit). Patients’ cognitive function and frailty status were assessed using validated instruments. Twenty-seven (61%) patients had CI and 61% were frail. The prevalence of dehydration at admission was 29% (n=12) and 19% (n=6) at study exit and dehydration status did not differ according to either CI status or frailty status. Within the non-CI group, however, significantly more frail than fit patients were dehydrated at admission (p=0.03). These findings indicate that dehydration is common amongst older hospital patients, and that frailty may increase the risk for dehydration in cognitively intact older patients.