Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma : clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

Background The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. Methods MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Findings Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. Interpretation In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. Funding Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust. © 2011 Elsevier Ltd.

Assessment of the effects of maternal exposure to heatwave on birth outcomes in Brisbane, Australia

Even though heatwave events have become more frequent and intense in most regions around the world, little is known about the impact of heatwave on birth outcomes. This thesis uses a population-based study design to investigate the relationship between maternal heatwave exposure and adverse birth outcomes in Brisbane, Australia. This study found that heatwave exposure at any stage of pregnancy can be harmful to fetal growth, and further increase the risk of adverse birth outcomes. Both short- and long-term effects of heatwave on adverse birth outcomes were found. The findings in this thesis may have significant public health implications.

Clinical outcomes, not clinical utility, should be the major consideration for saxagliptin with or without metformin

A recent review by Panagoulias and Doupis, published in Patient Preference and Adherence, concerned the saxagliptin/metformin fixed combination (SAXA/MET FDC), and was titled "Clinical utility in the treatment of type 2 diabetes with the saxagliptin/metformin fixed combination."1 This review concluded that "The SAXA/MET FDC is a patient-friendly, dosage-flexible, and hypoglycemia-safe regimen with very few adverse events and a neutral or even favorable effect on body weight. It achieves significant glycosylated hemoglobin A1c reduction helping the patient to achieve his/her individual glycemic goals."1

A systematic review of patient-reported outcome instruments of dermatologic adverse events associated with targeted cancer therapies

Purpose Dermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL. Methods A comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments. Results Thirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome-14 (HFS-14)). Conclusions While there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies.

Patients' outcomes related to person-centred nursing care in radiation oncology: A case study

Abstract Purpose The aim of this case study is to describe patients' responses to nursing care following the implementation of a person-centred model in a radiation oncology department. Method An instrumental case study design utilised surveys to collect data on a range of key patient outcomes: patient satisfaction (PSS), informational issues (RSEP), quality of life (FACT_G), comfort (RTCQ), and emotional status (HADS). This occurred at the beginning of, and twelve months following, the implementation of the new model of care. Results This study demonstrated that, although adverse effects of radiotherapy continue to affect patient well-being in the latter part of their course of radiation therapy, patients continue to be satisfied with nursing care. There were significant differences between groups in perceptions of the care environment and the use of the nurse as an acknowledged source of information are noteworthy, since these variables were key targets of the new model of care. The finding that nurses were seen by the post-implementation cohort as more likely to be a source of information is an important indicator that the nurses' presence was noted by patients, and they generally reported high levels of functioning despite undergoing a curative course of radiotherapy. Conclusion The person-centred nursing approach in the radiotherapy setting has contributed to some improvements in the provision of patient care. Aspects of this study may assist in planning further nursing interventions for patients undergoing radiotherapy for cancer, and continue to enhance the contribution of the radiation oncology nurse to improved patient outcomes.

Effects of a multiple health behavior change intervention for colorectal cancer survivors on psychosocial outcomes and quality of life: A randomized controlled trial

Background Multiple health behavior change can ameliorate adverse effects of cancer. Purpose The purpose of this study was to determine the effects of a multiple health behavior change intervention (CanChange) for colorectal cancer survivors on psychosocial outcomes and quality of life. Methods A total of 410 colorectal cancer survivors were randomized to a 6-month telephone-based health coaching intervention (11 sessions using acceptance and commitment therapy strategies focusing on physical activity, weight management, diet, alcohol, and smoking) or usual care. Posttraumatic growth, spirituality, acceptance, mindfulness, distress, and quality of life were assessed at baseline, 6 and 12 months. Results Significant intervention effects were observed for posttraumatic growth at 6 (7.5, p < 0.001) and 12 months (4.1, p = 0.033), spirituality at 6 months (1.8, p = 0.011), acceptance at 6 months (0.2, p = 0.005), and quality of life at 6 (0.8, p = 0.049) and 12 months (0.9, p = 0.037). Conclusions The intervention improved psychosocial outcomes and quality of life (physical well-being) at 6 months with most effects still present at 12 months. (Trial Registration Number: ACTRN12608000399392).

Evolution in design of integral leg prosthesis leads to improved outcomes

Developments of surgical attachments for bone-anchored prostheses are slowly but surely winning over the initial disbelief in the orthopedic community. Clearly, this option is becoming accessible to a wide range of individuals with limb loss. Seminal studies have demonstrated that the pioneering procedure relying on screw-type fixation engenders major clinical benefits and acceptable safety. The surgical procedure for press-fit implants, such as the Integral-Leg-Prosthesis (ILP) has been described Dr Aschoff and his team. Some clinical benefits of press-fit implants have been also established. Here, his team is once again taking a leading role by sharing the progression over 15 years of the rate of deep infections for 69 individuals with transfemoral amputation fitted with three successive refined versions of the ILP. By definition, a double-blind randomized clinical trial to test the effect of different fixation’s design is difficult. Alternatively, Juhnke and colleagues are reporting the outcomes of action-research study for a cohort of participants. The first and foremost important outcome of this study is the confirmation that the current design of the IPL and rehabilitation program are altogether leading to an acceptable rate of deep infection and other adverse events (e.g., structural failure of implant, periprosthetic factures). This study is also providing a strong insight onto the effect of major phases in redesign of an implant on the risk of infection. This is an important reminder that the development of a successful osseointegrated implant is unlikely to be immediate but the results of a learning curve made of empirical and sequential changes led by a reflective clinical practice. Clearly, this study provided better understanding of the safety of the ILP surgical and rehabilitation procedure while establishing standards and benchmark data for future studies focusing on design and infection of press-fit implants. Complementary observations of relationship between infection and cofounders such as loading of the prosthesis and prosthetic components used would be beneficial.Further definitive evidences of the clinical benefits with the latest design would be valuable, although an increase in health related quality of life and functional outcomes are likely to be confirmed. Altogether, the authors are providing compelling evidence that bone-anchored attachments particularly those relying on press-fit implants are an established alternative to socket prostheses.

The acceptability, usability and short-term outcomes of Get Real: A web-based program for psychotic-like experiences (PLEs)

Background Psychotic-like experiences (PLEs) are subclinical delusional ideas and perceptual disturbances that have been associated with a range of adverse mental health outcomes. This study reports a qualitative and quantitative analysis of the acceptability, usability and short term outcomes of Get Real, a web program for PLEs in young people. Methods Participants were twelve respondents to an online survey, who reported at least one PLE in the previous 3 months, and were currently distressed. Ratings of the program were collected after participants trialled it for a month. Individual semi-structured interviews then elicited qualitative feedback, which was analyzed using Consensual Qualitative Research (CQR) methodology. PLEs and distress were reassessed at 3 months post-baseline. Results User ratings supported the program's acceptability, usability and perceived utility. Significant reductions in the number, frequency and severity of PLE-related distress were found at 3 months follow-up. The CQR analysis identified four qualitative domains: initial and current understandings of PLEs, responses to the program, and context of its use. Initial understanding involved emotional reactions, avoidance or minimization, limited coping skills and non-psychotic attributions. After using the program, participants saw PLEs as normal and common, had greater self-awareness and understanding of stress, and reported increased capacity to cope and accept experiences. Positive responses to the program focused on its normalization of PLEs, usefulness of its strategies, self-monitoring of mood, and information putting PLEs into perspective. Some respondents wanted more specific and individualized information, thought the program would be more useful for other audiences, or doubted its effectiveness. The program was mostly used in low-stress situations. Conclusions The current study provided initial support for the acceptability, utility and positive short-term outcomes of Get Real. The program now requires efficacy testing in randomized controlled trials.

Lower preoperative quality of life increases postoperative risk of adverse events in women with endometrial cancer: results from the LACE trial

Objective: To examine the association between preoperative quality of life (QoL) and postoperative adverse events in women treated for endometrial cancer. Methods: 760 women with apparent Stage I endometrial cancer were randomised into a clinical trial evaluating laparoscopic versus open surgery. This analysis includes women with preoperative QoL measurements, from the Functional Assessment of Cancer Therapy- General (FACT-G) questionnaire, and who were followed up for at least 6 weeks after surgery (n=684). The outcomes for this study were defined as (1) the occurrence of moderate to severe AEs adverse events within 6 months (Common Toxicology Criteria (CTC) grade ≥3); and (2) any Serious Adverse Event (SAE). The association between preoperative QoL and the occurrence of AE was examined, after controlling for baseline comorbidity and other factors. Results: After adjusting for other factors, odds of occurrence of AE of CTC grade ≥3 were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.00-1.03, p=0.030), which was driven by physical well-being (PWB) (OR=1.09, 95% CI 1.04-1.13, p=0.0002) and functional well-being subscales (FWB) (OR=1.04, 95% CI 1.00-1.07, p=0.035). Similarly, odds of SAE occurrence were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.01-1.04, p=0.011), baseline PWB (OR=1.11, 95% CI 1.06-1.16, p<0.0001) or baseline FWB subscales (OR=1.05, 95% CI 1.01-1.10, p=0.0077). Conclusion: Women with early endometrial cancer presenting with lower QoL prior to surgery are at higher risk of developing a serious adverse event following surgery. Funding: Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council, Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women’s Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.

Performance based planning in Queensland : A case of unintended plan-making outcomes

Performance based planning (PBP) is purported to be a viable alternative to traditional zoning. The implementation of PBP ranges between pure approaches that rely on predetermined quantifiable performance standards to determine land use suitability, and hybrid approaches that rely on a mix of activity based zones in addition to prescriptive and subjective standards. Jurisdictions in the USA, Australia and New Zealand have attempted this type of land use regulation with varying degrees of success. Despite the adoption of PBP legislation in these jurisdictions, this paper argues that a lack of extensive evaluation means that PBP is not well understood and the purported advantages of this type of planning are rarely achieved in practice. Few empirical studies have attempted to examine how PBP has been implemented in practice. In Queensland, Australia, the Integrated Planning Act 1997 (IPA) operated as Queensland's principal planning legislation between March 1998 and December 2009. While the IPA did not explicitly use the term performance based planning, the Queensland's planning system is widely considered to be performance based in practice. Significantly, the IPA prevented Local Government from prohibiting development or use and the term zone was absent from the legislation. How plan-making would be advanced under the new planning regime was not clear, and as a consequence local governments produced a variety of different plan-making approaches to comply with the new legislative regime. In order to analyse this variation the research has developed a performance adoption spectrum to classify plans ranging between pure and hybrid perspectives of PBP. The spectrum compares how land use was regulated in seventeen IPA plans across Queensland. The research found that hybrid plans predominated, and that over time a greater reliance on risk adverse drafting approaches created a quasi-prohibition plan, the exact opposite of what was intended by the IPA. This paper concludes that the drafting of the IPA and absence of plan-making guidance contributed to lack of shared understanding about the intended direction of the new planning system and resulted in many administrative interpretations of the legislation. It was a planning direction that tried too hard to be different, and as a result created a perception of land use risk and uncertainty that caused a return to more prescriptive and inflexible plan-making methods.

Non-clinical outcomes of antiretroviral therapy for HIV/AIDS in developing countries: a systematic literature review

The impacts of antiretroviral therapy on quality of life, mental health, labor productivity, and economic wellbeing for people living with HIV/AIDS in developing countries are only beginning to be measured. We conducted a systematic literature review to analyze the effect of antiretroviral therapy (ART) on these non-clinical indicators in developing countries and assess the state of research on these topics. Both qualitative and quantitative studies were included, as were peer-reviewed articles, gray literature, and conference abstracts and presentations. Findings are reported from 12 full-length articles, 7 abstracts, and 1 presentation (representing 16 studies). Compared to HIV-positive patients not yet on treatment, patients on ART reported significant improvements in physical, emotional and mental health and daily function. Work performance improved and absenteeism decreased, with the most dramatic changes occurring in the first three months of treatment and then leveling off. Little research has been done on the impact of ART on household wellbeing, with modest changes in child and family wellbeing within households where adults are receiving ART reported so far. Studies from developing countries have not yet assessed non-clinical outcomes of therapy beyond the first year; therefore, longitudinal outcomes are still unknown. As ART roll out extends throughout high HIV prevalence, low-resource countries and is sustained over years and decades, both positive and adverse non-clinical outcomes need to be empirically measured and qualitatively explored in order to support patient adherence and maximize treatment benefits.

Cancer associated malnutrition: prevalence of cachexia, sarcopenia and impact on treatment outcomes, survival and health related quality of life

Malnutrition, sarcopenia and cancer cachexia (CC) are prevalent among cancer patients and can have detrimental effects on clinical outcomes such as quality of life (QoL) and overall survival. Cachexia is associated with lower tolerance for chemotherapy, which limits the total dose that can be delivered, the number of symptomatic responses and any survival advantage that might be accrued. Moreover, for the majority who do not respond, cachexia may be exacerbated by systemic chemotherapy, thus increasing the net symptom burden experienced by patients. The multitude of interactions between cancer location, treatments, nutritional status and QoL has never been thoroughly explored in an Irish cancer cohort. The objectives of this thesis were to further understand nutritional status, especially body composition in ambulatory cancer patients and determine the relationship between nutritional status using different assessment criteria and QoL, chemotherapy toxicity and survival among cancer patients undergoing chemotherapy. Results aimed to identify baseline factors that may be predictive of poor outcome, toxicities to chemotherapy and disease-free and overall survival. This thesis broadly divides into two sections. The first section (Chapters 3 & 4) focuses on improving our knowledge of the nutritional status of Irish cancer outpatients using a cross sectional study design. A study of 517 patients referred for chemotherapy was conducted using computed tomography (CT) imaging (body composition) and a survey that documented oncologic data, weight loss (WL) data and QoL data. We revealed that a significant proportion of Irish cancer patients undergoing chemotherapy experience unintentional WL over the previous 6 months (62%), sarcopenia (45%) and CC (43%), and the distribution of WL and nutritional risk were associated with site of primary tumour and treatment intent. Patients that had sarcopenia, nutritional risk, or CC had significantly reduced functional abilities, more symptoms and adverse global QoL. In the second section of this thesis (Chapters 5 & 6) the potential link between developing toxicity to antineoplastic regimens in patients with sarcopenia was conducted by way of retrospective studies. A retrospective serial CT analysis defined the prevalence of sarcopenia in patients with metastatic renal cell carcinoma (mRCC) and metastatic castrate resistant prostate cancer (mCRPC), which was then correlated with dose limiting toxicities of sunitinib and docetaxel respectively. Sarcopenia was prevalent in patients with mRCC and mCRPC, was an occult condition in patients with normal/high BMI, was associated with less treatment days, was a significant predictor of DLT in patients receiving sunitinib and a significant predictor of neutropenia and neurosensory toxicities in patients receiving docetaxel. This thesis attempted to address the underlying research deficiencies in Irish oncology nutritional data at national level. The findings from this thesis have implications for the planning of cancer care interventions and indicate that further research is required to improve nutritional screening, in particular for CC and sarcopenia, in the hope that timely intervention can improve both patient-centered and oncologic outcomes.

The influence of hepatic function on prostate cancer outcomes after radical prostatectomy.

Prostate growth is dependent on circulating androgens, which can be influenced by hepatic function. Liver disease has been suggested to influence prostate cancer (CaP) incidence. However, the effect of hepatic function on CaP outcomes has not been investigated. A total of 1181 patients who underwent radical prostatectomy (RP) between 1988 and 2008 at four Veterans Affairs hospitals that comprise the Shared Equal Access Regional Cancer Hospital database and had available liver function test (LFT) data were included in the study. Independent associations of LFTs with unfavorable pathological features and biochemical recurrence were determined using logistic and Cox regression analyses. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were elevated in 8.2 and 4.4% of patients, respectively. After controlling for CaP features, logistic regression revealed a significant association between SGOT levels and pathological Gleason sum > or =7(4+3) cancer (odds ratio=2.12; 95% confidence interval=1.11-4.05; P=0.02). Mild hepatic dysfunction was significantly associated with adverse CaP grade, but was not significantly associated with other adverse pathological features or biochemical recurrence in a cohort of men undergoing RP. The effect of moderate-to-severe liver disease on disease outcomes in CaP patients managed non-surgically remains to be investigated.

Air pollution, Fuel Usage and Health Outcomes in Madre de Dios, Peru: a Comparative Cross Sectional Study

Air pollution is a common problem. Particulate matter generated from air pollution has been tied to adverse health outcomes associated with cardiovascular disease. Biomass fuels are a specific contributor to increased particulate matter and arise as a result of indoor heating, cook stoves and indoor food preparation. This is a two part cross sectional study looking at communities in the Madre de Dios region. Survey data was collected from 9 communities along the Madre de Dios River. Individual level household PM2.5 was also collected as a means to generate average PM data stratified by fuel use. Data collection was affected by a number of outside factors, which resulted in a loss of data. Results from the cross-sectional study indicate that hypertension is not a significant source of morbidity. Obesity is prevalent and significantly associated with kitchen venting method indicating a potential relationship.

Nursing resources and patient outcomes in intensive care: a systematic review of the literature

Objectives: To evaluate the empirical evidence linking nursing resources to patient outcomes in intensive care settings as a framework for future research in this area. Background: Concerns about patient safely and the quality of care are driving research on the clinical and cost-effectiveness of health care interventions, including the deployment of human resources. This is particularly important in intensive care where a large proportion of the health care budget is consumed and where nursing staff is the main item of expenditure. Recommendations about staffing levels have been trade but may not be evidence based and may not always be achieved in practice. Methods: We searched systematically for studies of the impact of nursing resources (e.g. nurse-patient ratios, nurses' level of education, training and experience) on patient Outcomes, including mortality and adverse events, in adult intensive care. Abstracts of articles were reviewed and retrieved if they investigated the relationship between nursing resources and patient Outcomes. Characteristics of the studies were tabulated and the quality of the Studies assessed. Results: Of the 15 studies included in this review, two reported it statistical relationship between nursing resources and both mortality and adverse events, one reported ail association to mortality only, seven studies reported that they Could not reject the null hypothesis of no relationship to mortality and 10 studies (out of 10 that tested the hypothesis) reported a relationship to adverse events. The main explanatory mechanisms were the lack of time for nurses to perform preventative measures, or for patient surveillance. The nurses' role in pain control was noted by One author. Studies were mainly observational and retrospective and varied in scope from 1 to 52 units. Recommendations for future research include developing the mechanisms linking nursing resources to patient Outcomes, and designing large multi-centre prospective Studies that link patient's exposure to nursing care oil a shift-by-shift basis over time. (C) 2007 Elsevier Ltd. All rights reserved.