A comparison of treatment options for management of end stage kidney disease in elderly patients : a systematic review

Background Chronic kidney disease is a global public health problem of increasing prevalence. There are five stages of kidney disease, with Stage 5 indicating end stage kidney disease (ESKD) requiring dialysis or death will eventually occur. Over the last two decades there have been increasing numbers of people commencing dialysis. A majority of this increase has occurred in the population of people who are 65 years and over. With the older population it is difficult to determine at times whether dialysis will provide any benefit over non-dialysis management. The poor prognosis for the population over 65 years raises issues around management of ESKD in this population. It is therefore important to review any research that has been undertaken in this area which compares outcomes of the older ESKD population who have commenced dialysis with those who have received non-dialysis management. Objective The primary objective was to assess the effect of dialysis compared with non-dialysis management for the population of 65 years and over with ESKD. Inclusion criteria Types of participants This review considered studies that included participants who were 65 years and older. These participants needed to have been diagnosed with ESKD for greater than three months and also be either receiving renal replacement therapy (RRT) (hemodialysis [HD] or peritoneal dialysis [PD]) or non-dialysis management. The settings for the studies included the home, self-care centre, satellite centre, hospital, hospice or nursing home. Types of intervention(s)/phenomena of interest This review considered studies where the intervention was RRT (HD or PD) for the participants with ESKD. There was no restriction on frequency of RRT or length of time the participant received RRT. The comparator was participants who were not undergoing RRT. Types of studies This review considered both experimental and epidemiological study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies. This review also considered descriptive epidemiological study designs including case series, individual case reports and descriptive cross sectional studies for inclusion. This review included any of the following primary and secondary outcome measures: •Primary outcome – survival measures •Secondary outcomes – functional performance score (e.g. Karnofsky Performance score) •Symptoms and severity of end stage kidney disease •Hospital admissions •Health related quality of life (e.g. KDQOL, SF36 and HRQOL) •Comorbidities (e.g. Charlson Comorbidity index).

Management of atopic dermatitis in children : evaluation of parents' self-efficacy, outcome expectations, and self-reported task performance using the Child Eczema Management Questionnaire

Child behaviour management is crucial to successful treatment of atopic dermatitis. This study tested relationships between parents’ self-efficacy, outcome expectations, and self-reported task performance when caring for a child with atopic dermatitis. Using a cross-sectional study design, a community-based convenience sample of 120 parents participated in pilot-testing of the Child Eczema Management Questionnaire - a self-administered questionnaire which appraises parents’ self-efficacy, outcome expectations, and self-reported task performance when managing atopic dermatitis. Overall, parents’ self-reported confidence and success with performing routine management tasks was greater than that for managing their child’s symptoms and behaviour. Therewas a positive relationship between time since diagnosis and self-reported performance of routine management tasks; however, success with managing the child’s symptoms and behaviour did not improve with illness duration. Longer time since diagnosis was also associated with more positive outcome expectations of performing tasks that involved others in the child’s care (i.e. healthcare professionals, or the child themselves). This study provides the foundation for further research examining relationships between child, parent, and family psychosocial variables, parent management of atopic dermatitis, and child health outcomes. Improved understanding of these relationships will assist healthcare providers to better support parents and families caring for children with atopic dermatitis. KEYWORDS

Deriving a preference-based utility measure for cancer patients from the European Organisation for the Research and Treatment of Cancer's Quality of Life Questionnaire C30 : a confirmatory versus exploratory approach

Background Multi attribute utility instruments (MAUIs) are preference-based measures that comprise a health state classification system (HSCS) and a scoring algorithm that assigns a utility value to each health state in the HSCS. When developing a MAUI from a health-related quality of life (HRQOL) questionnaire, first a HSCS must be derived. This typically involves selecting a subset of domains and items because HRQOL questionnaires typically have too many items to be amendable to the valuation task required to develop the scoring algorithm for a MAUI. Currently, exploratory factor analysis (EFA) followed by Rasch analysis is recommended for deriving a MAUI from a HRQOL measure. Aim To determine whether confirmatory factor analysis (CFA) is more appropriate and efficient than EFA to derive a HSCS from the European Organisation for the Research and Treatment of Cancer’s core HRQOL questionnaire, Quality of Life Questionnaire (QLQ-C30), given its well-established domain structure. Methods QLQ-C30 (Version 3) data were collected from 356 patients receiving palliative radiotherapy for recurrent/metastatic cancer (various primary sites). The dimensional structure of the QLQ-C30 was tested with EFA and CFA, the latter informed by the established QLQ-C30 structure and views of both patients and clinicians on which are the most relevant items. Dimensions determined by EFA or CFA were then subjected to Rasch analysis. Results CFA results generally supported the proposed QLQ-C30 structure (comparative fit index =0.99, Tucker–Lewis index =0.99, root mean square error of approximation =0.04). EFA revealed fewer factors and some items cross-loaded on multiple factors. Further assessment of dimensionality with Rasch analysis allowed better alignment of the EFA dimensions with those detected by CFA. Conclusion CFA was more appropriate and efficient than EFA in producing clinically interpretable results for the HSCS for a proposed new cancer-specific MAUI. Our findings suggest that CFA should be recommended generally when deriving a preference-based measure from a HRQOL measure that has an established domain structure.

The effect of the addition of hip strengthening exercises to a lumbopelvic exercise programme for the treatment of non-specific low back pain : a randomized controlled trial

Objectives To compare the efficacy of two exercise programs in reducing pain and disability for individuals with non-specific low back pain and to examine the underlying mechanical factors related to pain and disability for individuals with NSLBP. Design A single-blind, randomized controlled trial. Methods: Eighty participants were recruited from eleven community-based general medical practices and randomized into two groups completing either a lumbopelvic motor control or a combined lumbopelvic motor control and progressive hip strengthening exercise therapy program. All participants received an education session, 6 rehabilitation sessions including real time ultrasound training, and a home based exercise program manual and log book. The primary outcomes were pain (0-100mm visual analogue scale), and disability (Oswestry Disability Index V2). The secondary outcomes were hip strength (N/kg) and two-dimensional frontal plane biomechanics (°) measure during the static Trendelenburg test and while walking. All outcomes were measured at baseline and at 6-week follow up. Results There was no statistical difference in the change in pain (xˉ = -4.0mm, t= -1.07, p =0.29, 95%CI -11.5, 3.5) or disability (xˉ = -0.3%, t= -0.19, p =0.85, 95%CI -3.5, 2.8) between groups. Within group comparisons revealed clinically meaningful reductions in pain for both Group One (xˉ =-20.9mm, 95%CI -25.7, -16.1) and Group Two (xˉ =-24.9, 95%CI -30.8, -19.0). Conclusion Both exercise programs had similar efficacy in reducing pain. The addition of hip strengthening exercises to a motor control exercise program does not appear to result in improved clinical outcome for pain for individuals with non-specific low back pain.

What patient information allows us to make accurate predictions of outcome?

Only some of the information contained in a medical record will be useful to the prediction of patient outcome. We describe a novel method for selecting those outcome predictors which allow us to reliably discriminate between adverse and benign end results. Using the area under the receiver operating characteristic as a nonparametric measure of discrimination, we show how to calculate the maximum discrimination attainable with a given set of discrete valued features. This upper limit forms the basis of our feature selection algorithm. We use the algorithm to select features (from maternity records) relevant to the prediction of failure to progress in labour. The results of this analysis motivate investigation of those predictors of failure to progress relevant to parous and nulliparous sub-populations.

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.

Effects of anticoagulants on outcome of femoral neck fracture surgery

PURPOSE To review records of 330 patients who underwent surgery for femoral neck fractures with or without preoperative anticoagulation therapy. METHODS Medical records of 235 women and 95 men aged 48 to 103 years (mean, 81.6; standard deviation [SD], 13.1) who underwent surgery for femoral neck fractures with or without preoperative anticoagulation therapy were reviewed. 30 patients were on warfarin, 105 on aspirin, 28 on clopidogrel, and 167 were controls. The latter 3 groups were combined as the non-warfarin group and compared with the warfarin group. Hospital mortality, time from admission to surgery, length of hospital stay, return to theatre, and postoperative complications (wound infection, deep vein thrombosis, and pulmonary embolism) were assessed. RESULTS The warfarin and control groups were significantly younger than the clopidogrel and aspirin groups (80.8 vs. 80.0 vs. 84.2 vs. 83.7 years, respectively, p<0.05). 81% of the patients underwent surgery within 48 hours of admission. The overall mean time from admission to surgery was 1.8 days; it was longer in the warfarin than the aspirin, clopidogrel, and control groups (3.3 vs. 1.8 vs. 1.6 vs. 1.6 days, respectively, p<0.001). The mean length of hospital stay was 17.5 (SD, 9.6; range, 3-54) days. The overall hospital mortality was 3.9%; it was 6.7% in the warfarin group, 3.8% in the aspirin group, 3.6% in the clopidogrel group, and 3.6% in the control group (p=0.80). Four patients returned to theatre for surgery: one in the warfarin group for washout of a haematoma, 2 in the aspirin group for repositioning of a mal-fixation and for debridement of wound infection, and one in the control group for debridement of wound infection. The warfarin group did not differ significantly from non-warfarin group in terms of postoperative complication rate (6.7% vs. 2.7%, p=0.228) and the rate of return to theatre (3.3% vs. 1%, p=0.318). CONCLUSION It is safe to continue aspirin and clopidogrel prior to surgical treatment for femoral neck fracture. The risk of delaying surgery outweighs the peri-operative bleeding risk.

Pituitary volume and early treatment response in drug-naïve first-episode psychosis patients

BACKGROUND: An early response to antipsychotic treatment in patients with psychosis has been associated with a better course and outcome. However, factors that predict treatment response are not well understood. The onset of schizophrenia and related disorders has been associated with increased levels of stress and hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis. This study examined whether pituitary volume at the onset of psychosis may be a potential predictor of early treatment response in first-episode psychosis (FEP) patients. METHODS: We investigated the relationship between baseline pituitary volume and symptomatic treatment response over 12 weeks using mixed model analysis in a sample of 42 drug-naïve or early treated FEP patients who participated in a controlled dose-finding study of quetiapine fumarate. Logistic regression was used to examine predictors of treatment response. Pituitary volume was measured from magnetic resonance imaging scans that were obtained upon entry into the trial. RESULTS: Larger pituitary volume was associated with less improvement in overall psychotic symptoms (Brief Psychiatric Rating Scale (BPRS) P=0.031) and positive symptoms (BPRS positive symptom subscale P=0.010). Regardless of gender, patients with a pituitary volume at the 25th percentile (413 mm(3)) were approximately three times more likely to respond to treatment by week 12 than those at the 75th percentile (635 mm(3)) (odds ratio=3.07, CI: 0.90-10.48). CONCLUSION: The association of baseline pituitary volumes with early treatment response highlights the importance of the HPA axis in emerging psychosis. Potential implications for treatment strategies in early psychosis are discussed.

Are we waiting too long for the cardiovascular outcome trials with the glucagon-like peptide-1 receptor agonists?

Several new medicines are in development for the treatment of type 2 diabetes, and cardiovascular outcome trials are the gold standard for these medicines. This editorial demonstrates that despite being available for over 10 years, there are no cardiovascular outcome studies for any of the glucagon-like peptide-1 (GLP-1) receptor agonists, which demonstrate cardiovascular safety or benefit in subjects with high cardiovascular risk. The author argues that the FDA should be ensuring that clinical outcome studies for subjects with type 2 diabetes and high cardiovascular risk be undertaken in a timelier manner.

The short-term impact of curative colorectal cancer treatment on physical activity, functional status and quality of life: A systematic review protocol

REVIEW QUESTION/OBJECTIVE The quantitative objectives are to identify the impact of curative colorectal cancer treatment (surgery or adjuvant therapy) on physical activity, functional status and quality of life within one year of treatment or diagnosis. INCLUSION CRITERIA Types of participants: This review will consider studies that include individuals aged 18 years and over who have been diagnosed with colorectal cancer. Types of intervention(s)/phenomena of interest: This review will consider studies that evaluate the impact of curative colorectal cancer treatment: surgery and/or adjuvant therapy. Types of outcomes: This review will consider studies that include the following outcome measures assessed within one year of diagnosis or treatment: Physical activity - any bodily movement produced by skeletal muscles resulting in energy expenditure. Physical activity is not exclusive to exercise; activities can also be walking, housework, occupational or leisure. Physical activity can be measured objectively using pedometers or accelerometers, or subjectively using self-reported measures. Functional status – measured as the capacity to perform all activities of daily living such as walking, showering, and eating; and instrumental activities of daily living such as (but not limited to) grocery shopping, housekeeping and laundry. Quality of life – defined as the individual meaning of mental, physical and psychosocial wellbeing, as measured by validated tools such as SF-36, EORTC-QLQ-C30, or FACT-C.

Review of the evidence of lymphedema treatment effect

Lymphedema treatment aims to alleviate symptoms, prevent progression and reduce risk of skin infection. Mainstream treatment options have been investigated in over 160 studies. Findings from these studies have been included in at least one of more than 20 literature reviews. A critique of these reviews was undertaken to summarise efficacy findings. The quality of the reviews was evaluated and gaps in the research identified, to better guide clinical practice. Overall, there was wide variation in review methods. The quality of studies included in reviews, in terms of study design and reporting overall has been poor. Reviews consistently concluded that complex physical therapy is effective at reducing limb volume. Volume reductions were also reported following the use of compression garments, pumps and manual lymphatic drainage. However, greatest improvements were reported when these treatments formed a combined treatment program. Large, well-designed, evaluated and reported randomised, controlled trials are needed to evaluate and compare treatments. Consistent outcome measures will allow better quality reviews and meta-analysis in the future.

Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: A case study for technology appraisal on the basis of surrogate outcomes evidence

Objectives In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence’s recommendation on the public funding of these first-line treatments for CML. Methods We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR. Results Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21–23 years) following first-line treatment with imatinib, dasatinib, or nilotinib. Conclusions This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).

Does the addition of Clonidine to lumbar nerve root blocks improve outcome? A randomised, prospective, single-blinded controlled pilot study

Purpose To evaluate if adding clonidine to a standard nerve root block containing local anaesthetic and steroid improved the outcome of patients with severe lumbar nerve root pain secondary to MRI proven lumbar disc prolapse. Methods We undertook a single blind, prospective, randomised controlled trial evaluating 100 consecutive patients with nerve root pain secondary to lumbar disc prolapse undergoing trans-foraminal epidural steroid injection either with or without the addition of clonidine. 50 patients were allocated to each arm of the study. The primary outcome measure was the avoidance of a second procedure- repeat injection or micro-discectomy surgery. Secondary outcome measures were also studied: pain scores for leg and back pain using a visual analogue scale (VAS), the Roland Morris Disability Questionnaire (RMDQ) and the Measure Your Own Medical Outcome Profile (MYMOP). Follow up was carried out at 6 weeks, 6 months and 1 year. Results No serious complications occurred. Of the 50 patients who received the addition of clonidine, 56% were classified as successful injections, with no further intervention required, as opposed to 40% who received the standard injection. This difference did not reach statistical significance (p=0.109, chi-squared test). All secondary measures showed no statistically significant differences between the groups except curiously, the standard group who had been classified as successful had better leg pain relief than the clonidine group (p=0.026) at 1 year. Conclusions This pilot study has shown a 16% treatment effect with adding clonidine to lumbar nerve root blocks and that it is a safe injectate for this purpose.

Consensus statement on the role of Accredited Exercise Physiologists within the treatment of mental disorders: A guide for mental health professionals

- Objective The aim is to identify the role and scope of Accredited Exercise Physiologist (AEP) services in the mental health sector and to provide insight as to how AEPs can contribute to the multidisciplinary mental health team. - Methods A modified Delphi approach was utilised. Thirteen AEPs with experience in mental health contributed to the iterative development of a national consensus statement. Six mental health professionals with expertise in psychiatry, mental health nursing, general practice and mental health research participated in the review process. Reviewers were provided with a template to systematically provide feedback on the language, content, structure and relevance to their professional group. - Results This consensus statement outlines how AEPs can contribute to the multidisciplinary mental health team, the aims and scope of AEP-led interventions in mental health services and examples of such interventions, the range of physical and mental health outcomes possible through AEP-led interventions and common referral pathways to community AEP services. - Outcome AEPs can play a key role in the treatment of individuals experiencing mental illness. The diversity of AEP interventions allows for a holistic approach to care, enhancing both physical and mental health outcomes.

A multi-centre open-label randomised non-inferiority trial comparing watchful waiting to antibiotic treatment for acute otitis media without perforation in low-risk urban Aboriginal and Torres Strait Islander children (the WATCH trial): study protocol for a randomised controlled trial

Background Treatment guidelines recommend watchful waiting for children older than 2 years with acute otitis media (AOM) without perforation, unless they are at high risk of complications. The high prevalence of chronic suppurative otitis media (CSOM) in remote Aboriginal and Torres Strait Islander communities leads these children to be classified as high risk. Urban Aboriginal and Torres Strait Islander children are at lower risk of complications, but evidence to support the subsequent recommendation for watchful waiting in this population is lacking. Methods/Design This non-inferiority multi-centre randomised controlled trial will determine whether watchful waiting is non-inferior to immediate antibiotics for urban Aboriginal and Torres Strait Islander children with AOM without perforation. Children aged 2 − 16 years with AOM who are considered at low risk for complications will be recruited from six participating urban primary health care services across Australia. We will obtain informed consent from each participant or their guardian. The primary outcome is clinical resolution on day 7 (no pain, no fever of at least 38 °C, no bulging eardrum and no complications of AOM such as perforation or mastoiditis) as assessed by general practitioners or nurse practitioners. Participants and outcome assessors will not be blinded to treatment. With a sample size of 198 children in each arm, we have 80 % power to detect a non-inferiority margin of up to 10 % at a significance level of 5 %, assuming clinical improvement of at least 80 % in both groups. Allowing for a 20 % dropout rate, we aim to recruit 495 children. We will analyse both by intention-to-treat and per protocol. We will assess the cost- effectiveness of watchful waiting compared to immediate antibiotic prescription. We will also report on the implementation of the trial from the perspectives of parents/carers, health professionals and researchers. Discussion The trial will provide evidence for the safety and effectiveness of watchful waiting for the management of AOM in Aboriginal and Torres Strait Islander children living in urban settings who are considered to be at low risk of complications.