Patterns of service utilisation within Australian hepatology clinics: High prevalence of advanced liver disease

Accepted Article Abstract Background: Liver diseases in Australia are estimated to affect 6 million people with a societal cost of $51 billion annually. Information about utilization of specialist hepatology care is critical in informing policy makers about the requirements for delivery of hepatology-related health care. Aims: This study examined etiology and severity of liver disease seen in a tertiary hospital hepatology clinic, as well as resource utilisation patterns. Methods: A longitudinal cohort study included consecutive patients booked in hepatology outpatient clinics during a 3 month period. Subsequent outpatient appointments for these patients over the following 12 months were then recorded. Results: During the initial 3 month period 1471 appointments were scheduled with a hepatologist, 1136 of which were attended. 21% of patients were “new cases”. Hepatitis B (HBV) was the most common disease etiology for new cases (37%). Advanced disease at presentation varied between etiology, with HBV (5%), Hepatitis C (HCV) (31%), non-alcoholic fatty liver disease (NAFLD) (46%) and alcoholic liver disease (ALD) (72%). Most patients (83%) attended multiple hepatology appointments, and a range of referrals patterns for procedures, investigations and other specialty assessments were observed. Conclusions: There is a high prevalence of HBV in new case referrals. Patients with HCV, NAFLD and ALD have a high prevalence of advanced liver disease at referral, requiring ongoing surveillance for development of decompensated liver disease and liver cancer. These findings that describe patterns of health service utilisation among patients with liver disease provide useful information for planning sustainable health service provision for this clinical population

Identifying advanced practice: A national survey of a nursing workforce

Background The size and flexibility of the nursing workforce has positioned nursing as central to the goals of health service improvement. Nursing's response to meeting these goals has resulted in proliferation of advanced practice nursing with a confusing array of practice profiles, titles and roles. Whilst numerous models and definitions of advanced practice nursing have been developed there is scant published research of significant scope that supports these models. Consequently there is an ongoing call in the literature for clarity and stability in nomenclature, and confusion in the health industry on how to optimise the utility of advanced practice nursing. Objectives To identify and delineate advanced practice from other levels of nursing practice through examination of a national nursing workforce. Design A cross-sectional electronic survey of nurses using the validated Advanced Practice Role Delineation tool based on the Strong Model of Advanced Practice. Participants Study participants were registered nurses employed in a clinical service environment across all states and territories of Australia. Methods A sample of 5662 registered nurses participated in the study. Domain means for each participant were calculated then means for nursing position titles were calculated. Position titles were grouped by delineation and were compared with one-way analysis of variance on domain means. The alpha for all tests was set at 0.05. Significant effects were examined with Scheffe post hoc comparisons to control for Type 1 error. Results The survey tool was able to identify position titles where nurses were practicing at an advanced level and to delineate this cohort from other levels of nursing practice, including nurse practitioner. The results show that nurses who practice at an advanced level are characterised by high mean scores across all Domains of the Strong Model of Advanced Practice. The mean scores of advanced practice nurses were significantly different from nurse practitioners in the Direct Care Domain and significantly different from other levels of nurse across all domains. Conclusions The study results show that the nurse practitioner, advanced practice nurse and foundation level registered nurse have different patterns of practice and the Advanced Practice Role Delineation tool has the capacity to clearly delineate and define advanced practice nursing. These findings make a significant contribution to the international debate and show that the profession can now identify what is and what is not advanced practice in nursing.

Forgery attacks on ++AE authenticated encryption mode

In this paper, we analyse a block cipher mode of operation submitted in 2014 to the cryptographic competition for authenticated encryption (CAESAR). This mode is designed by Recacha and called ++AE (plus-plus-ae). We propose a chosen plaintext forgery attack on ++AE that requires only a single chosen message query to allow an attacker to construct multiple forged messages. Our attack is deterministic and guaranteed to pass ++AE integrity check. We demonstrate the forgery attack using 128-bit AES as the underlying block cipher. Hence, ++AE is insecure as an authenticated encryption mode of operation.

Initialisation flaws in the A5-GMR-1 satphone encryption algorithm

A5-GMR-1 is a synchronous stream cipher used to provide confidentiality for communications between satellite phones and satellites. The keystream generator may be considered as a finite state machine, with an internal state of 81 bits. The design is based on four linear feedback shift registers, three of which are irregularly clocked. The keystream generator takes a 64-bit secret key and 19-bit frame number as inputs, and produces an output keystream of length between $2^8$ and $2^{10}$ bits. Analysis of the initialisation process for the keystream generator reveals serious flaws which significantly reduce the number of distinct keystreams that the generator can produce. Multiple (key, frame number) pairs produce the same keystream, and the relationship between the various pairs is easy to determine. Additionally, many of the keystream sequences produced are phase shifted versions of each other, for very small phase shifts. These features increase the effectiveness of generic time-memory tradeoff attacks on the cipher, making such attacks feasible.

Fatigue self-management behaviors in patients with advanced cancer: A prospective longitudinal survey

Purpose: To explore the fatigue self-management behaviors and factors associated with effectiveness of these behaviors in patients with advanced cancer. Design: Prospective longitudinal interviewer-administered survey. Setting: A tertiary cancer center in Queensland Australia. Sample: One hundred fifty two outpatients with metastatic breast, lung, colorectal and prostate cancer experiencing fatigue (>3/10) were recruited. Main Research Variables: Fatigue self-management behaviors outcomes (perceived effectiveness, self-efficacy and frequency), medical/demographic characteristics (including sites of primary cancer and metastasis, comorbidity, performance status), social support, depressive, anxiety, and other symptoms were assessed. Findings: The participants reported moderate levels of fatigue at baseline (M=5.85, SD 1.44), and maintained moderate levels at 4 weeks and 8 weeks. On average, participants consistently used approximately nine behaviors at each time point. Factors significantly associated with higher levels of perceived effectiveness of fatigue self-management behaviors were higher self-efficacy (p<.001), higher education level (p=.02), and lower levels of depressive symptoms (p=.04). Conclusions: The findings of this study demonstrate that patients with cancer, even with advanced disease, still want and are able to use a number of behaviors to control their fatigue. Self-management interventions that aim to enhance self-efficacy and address any concurrent depressive symptoms have the potential to reduce fatigue severity. Implications for Nursing: Nurses are well positioned to play a key role in supporting patients in their fatigue self-management. Knowledge Translation: This study particularly focused on the perspectives of patients about fatigue self-management, highlighting a number of issues requiring further attention in clinical practice and the potential for future research.

Which patients with chronic kidney disease have the greatest symptom burden? A comparative study of advanced CKD stage and dialysis modality

Background Chronic kidney disease (CKD) leads to a range of symptoms, which are often under-recognised and little is known about the multidimensional symptom experience in advanced CKD. Objectives To examine (1) symptom burden at CKD stages 4 and 5, and dialysis modalities, and (2) demographic and renal history correlates of symptom burden. Methods Using a cross-sectional design, a convenience sample of 436 people with CKD was recruited from three hospitals. The CKD Symptom Burden Index (CKD-SBI) was used to measure the prevalence, severity, distress and frequency of 32 symptoms. Demographic and renal history data were also collected. Results Of the sample, 75.5 % were receiving dialysis (haemodialysis, n = 287; peritoneal dialysis, n = 42) and 24.5 % were not undergoing dialysis (stage 4, n = 69; stage 5, n = 38). Participants reported an average of 13.01 ± 7.67 symptoms. Fatigue and pain were common and burdensome across all symptom dimensions. While approximately one-third experienced sexual symptoms, when reported these symptoms were frequent, severe and distressing. Haemodialysis, older age and being female were independently associated with greater symptom burden. Conclusions In CKD, symptom burden is better understood when capturing the multidimensional aspects of a range of physical and psychological symptoms. Fatigue, pain and sexual dysfunction are key contributors to symptom burden, and these symptoms are often under-recognised and warrant routine assessment. The CKD-SBI offers a valuable tool for renal clinicians to assess symptom burden, leading to the commencement of timely and appropriate interventions.

Measuring the multidimensions of symptoms in people with advanced stages of chronic kidney disease

Chronic kidney disease (CKD) is increasing globally and in Saudi Arabia it affects approximately 8% annual increment of dialysis population. It is associated with a high symptom burden. Previous studies have largely reported on the prevalence of symptoms only in the haemodialysis population. This study examined symptom burden across disease stages and treatment groups in advanced CKD, and their correlation with demographic and clinical factors. Using a cross-sectional design, a convenience sample of 436 patients with CKD was recruited from three hospitals in Saudi Arabia. The CKD Symptom Burden Index (CKD-SBI) was used to measure 32 CKD symptoms. Demographic and clinical data were also collected. Of the sample 75.5% were receiving dialysis (haemodialysis, n = 287; peritoneal dialysis, n = 42) and 24.5% were non-dialysis (CKD stage 4, n = 69; CKD stage 5, n = 38). Average symptom reported was 13.01 ± 7.67. Fatigue and pain were common and burdensome across all symptom dimensions.Approximately one-third of participants experienced sexual symptoms. Dialysis patients reported greater symptom burden, especially patients on haemodialysis. Haemodialysis treatment, older age and being female were independently associated with greater total symptom burden. In conclusion, symptom burden is high among advanced stages of CKD, particularly among those receiving dialysis. Although fatigue, pain and sexual dysfunction are key contributors to symptom burden in CKD, these symptoms are often under-recognised and warrant routine assessment. The CKD-SBI offers a valuable tool to assess symptom burden, leading to the commencement of timely and appropriate interventions.

Low-impact Use: A New Standard

Once the ugly duckling of the lighting world, the fluorescent bulb recently has become something of an eco-darling thanks to its energy efficiency. Whereas a standard off-the-shelf incandescent bulb devotes only about five percent of its total electrical consumption to produce visible light (the remainder is released in heat), fluorescent lighting employs an entirely different process (it radiates rather than burns) that is four to six times more efficient. Fluorescents are indisputably superior in ­performance, but up to 5 milligrams of mercury, a hazardous trace metal, is included in the manufacture of each lamp

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).

2nd ESMO Consensus Conference in Lung Cancer: Locally advanced stage III non-small-cell lung cancer

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.