Forward osmosis as a pre-treatment for treating coal seam gas associated water: Flux and fouling behaviours

In this study, a bench scale forward osmosis (FO) process was operated using two commonly available FO membranes in different orientations in order to examine the removal of foulants in the coal seam gas (CSG) associated water, the water flux and fouling behaviours of the process were also investigated. After 48 h of fouling simulation experiment, the water flux declined by approximately 55 and 35% of its initial level in the TFC-PRO and CTA-PRO modes (support layer facing the feed), respectively, while the flux decline in the TFC-FO and CTA-FO modes (active layer facing the feed) was insignificant. The flux decline in PRO modes was caused by the compounding effects of internal concentration polarisation and membrane fouling. However, the declined flux was completely recovered to its initial level following the hydraulic cleaning using deionised water. Dissolved organic carbon (DOC), adenosine tri-phosphate (ATP) and major inorganic scalants (Ca, Mg and silica) in the CSG feed were effectively removed by using the FO process. The results of this study suggest that the FO process shows promising potential to be employed as an effective pre-treatment for membrane purification of CSG associated water.

Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study

Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. Design Meta-epidemiological study. Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. Study selection Two independent reviewers selected trials. Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.

Dasatinib, nilotinib and standard-dose imatinib for the first line treatment of chronic myeloid leukaemia: Systematic reviews and economic analyses

- Background Nilotinib and dasatinib are now being considered as alternative treatments to imatinib as a first-line treatment of chronic myeloid leukaemia (CML). - Objective This technology assessment reviews the available evidence for the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of Philadelphia chromosome-positive CML. - Data sources Databases [including MEDLINE (Ovid), EMBASE, Current Controlled Trials, ClinicalTrials.gov, the US Food and Drug Administration website and the European Medicines Agency website] were searched from search end date of the last technology appraisal report on this topic in October 2002 to September 2011. - Review methods A systematic review of clinical effectiveness and cost-effectiveness studies; a review of surrogate relationships with survival; a review and critique of manufacturer submissions; and a model-based economic analysis. - Results Two clinical trials (dasatinib vs imatinib and nilotinib vs imatinib) were included in the effectiveness review. Survival was not significantly different for dasatinib or nilotinib compared with imatinib with the 24-month follow-up data available. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were higher for patients receiving dasatinib than for those with imatinib for 12 months' follow-up (CCyR 83% vs 72%, p < 0.001; MMR 46% vs 28%, p < 0.0001). The rates of CCyR and MMR were higher for patients receiving nilotinib than for those receiving imatinib for 12 months' follow-up (CCyR 80% vs 65%, p < 0.001; MMR 44% vs 22%, p < 0.0001). An indirect comparison analysis showed no difference between dasatinib and nilotinib for CCyR or MMR rates for 12 months' follow-up (CCyR, odds ratio 1.09, 95% CI 0.61 to 1.92; MMR, odds ratio 1.28, 95% CI 0.77 to 2.16). There is observational association evidence from imatinib studies supporting the use of CCyR and MMR at 12 months as surrogates for overall all-cause survival and progression-free survival in patients with CML in chronic phase. In the cost-effectiveness modelling scenario, analyses were provided to reflect the extensive structural uncertainty and different approaches to estimating OS. First-line dasatinib is predicted to provide very poor value for money compared with first-line imatinib, with deterministic incremental cost-effectiveness ratios (ICERs) of between £256,000 and £450,000 per quality-adjusted life-year (QALY). Conversely, first-line nilotinib provided favourable ICERs at the willingness-to-pay threshold of £20,000-30,000 per QALY. - Limitations Immaturity of empirical trial data relative to life expectancy, forcing either reliance on surrogate relationships or cumulative survival/treatment duration assumptions. - Conclusions From the two trials available, dasatinib and nilotinib have a statistically significant advantage compared with imatinib as measured by MMR or CCyR. Taking into account the treatment pathways for patients with CML, i.e. assuming the use of second-line nilotinib, first-line nilotinib appears to be more cost-effective than first-line imatinib. Dasatinib was not cost-effective if decision thresholds of £20,000 per QALY or £30,000 per QALY were used, compared with imatinib and nilotinib. Uncertainty in the cost-effectiveness analysis would be substantially reduced with better and more UK-specific data on the incidence and cost of stem cell transplantation in patients with chronic CML. - Funding The Health Technology Assessment Programme of the National Institute for Health Research.

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).

Focal brachytherapy treatment planning using multi-parametric MRI and biological dose optimisation

We describe a novel approach to treatment planning for focal brachytherapy utilizing a biologically based inverse optimization algorithm and biological imaging to target an ablative dose at known regions of significant tumour burden and a lower, therapeutic dose to low risk regions.

Doctors’ perspectives on law and life-sustaining treatment: Survey design and recruitment strategies for a challenging cohort

- Background Palliative medicine and other specialists play significant legal roles in decisions to withhold and withdraw life-sustaining treatment at the end of life. Yet little is known about their knowledge of or attitudes to the law, and the role they think it should play in medical practice. Consideration of doctors’ views is critical to optimizing patient outcomes at the end of life. However, doctors are difficult to engage as participants in empirical research, presenting challenges for researchers seeking to understand doctors’ experiences and perspectives. - Aims To determine how to engage doctors involved in end-of-life care in empirical research about knowledge of the law and the role it plays in medical practice at the end of life. - Methods Postal survey of all specialists in palliative medicine, emergency medicine, geriatric medicine, intensive care, medical oncology, renal medicine, and respiratory medicine in three Australian states: New South Wales, Victoria, and Queensland. The survey was sent in hard copy with two reminders and a follow up reminder letter was also sent to the directors of hospital emergency departments. Awareness was further promoted through engagement with the relevant medical colleges and publications in professional journals; various incentives to respond were also used. The key measure is the response rate of doctors to the survey. - Results Thirty-two percent of doctors in the main study completed their survey with response rate by specialty ranging from 52% (palliative care) to 24% (medical oncology). This overall response rate was twice that of the reweighted pilot study (16%). - Conclusions Doctors remain a difficult cohort to engage in survey research but strategic recruitment efforts can be effective in increasing response rate. Collaboration with doctors and their professional bodies in both the development of the survey instrument and recruitment of participants is essential.

The association of chronic kidney disease and dialysis treatment with foot ulceration and major amputation

Objective The objective of this study was to investigate the risk of chronic kidney disease (CKD) stage 4-5 and dialysis treatment on incidence of foot ulceration and major lower extremity amputation in comparison to CKD stage 3. Methods In this retrospective study, all individuals who visited our hospital between 2006 and 2012 because of CKD stages 3 to 5 or dialysis treatment were included. Medical records were reviewed for incidence of foot ulceration and major amputation. The time from CKD 3, CKD 4-5, and dialysis treatment until first foot ulceration and first major lower extremity amputation was calculated and analyzed by Kaplan-Meier curves and multivariate Cox proportional hazards model. Diabetes mellitus, peripheral arterial disease, peripheral neuropathy, and foot deformities were included for potential confounding. Results A total of 669 individuals were included: 539 in CKD 3, 540 in CKD 4-5, and 259 in dialysis treatment (individuals could progress from one group to the next). Unadjusted foot ulcer incidence rates per 1000 patients per year were 12 for CKD 3, 47 for CKD 4-5, and 104 for dialysis (P < .001). In multivariate analyses, the hazard ratio for incidence of foot ulceration was 4.0 (95% confidence interval [CI], 2.6-6.3) in CKD 4-5 and 7.6 (95% CI, 4.8-12.1) in dialysis treatment compared with CKD 3. Hazard ratios for incidence of major amputation were 9.5 (95% CI, 2.1-43.0) and 15 (95% CI, 3.3-71.0), respectively. Conclusions CKD 4-5 and dialysis treatment are independent risk factors for foot ulceration and major amputation compared with CKD 3. Maximum effort is needed in daily clinical practice to prevent foot ulcers and their devastating consequences in all individuals with CKD 4-5 or dialysis treatment.

Diabetic charcot neuroarthropathy of the knee: Conservative treatment options as alternatives to surgery

In contrast to the well-known Charcot neuroarthropathy (CN) of the foot, CN of the knee is hardly recognized. In a literature search, we only found five articles on total knee arthroplasty for Charcot joints (1–5). We did not find a single article dealing with alternative treatment options or the general clinical course of this disease. We started our study

Diabetic charcot neuroarthropathy of the hand: Clinical course, diagnosis, and treatment options

During the treatment of diabetic Charcot neuroarthropathy (CN) of the foot in two young patients, we discovered atypical alterations of their hands with loss of strength and paresthesia combined with atypical and nonhealing bone alterations and instability. Whereas CN of the foot is a serious and well-known complication of diabetes, CN of the hand is only mentioned in four articles (1–4).

Applicability of pebble matrix filtration for the pre-treatment of surface waters containing high turbidity and NOM

Purification of drinking water is routinely achieved by use of conventional coagulants and disinfection procedures. However, there are instances such as flood events when the level of turbidity reaches extreme levels while NOM may be an issue throughout the year. Consequently, there is a need to develop technologies which can effectively treat water of high turbidity during flood events and natural organic matter (NOM) content year round. It was our hypothesis that pebble matrix filtration potentially offered a relatively cheap, simple and reliable means to clarify such challenging water samples. Therefore, a laboratory scale pebble matrix filter (PMF) column was used to evaluate the turbidity and natural organic matter (NOM) pre-treatment performance in relation to 2013 Brisbane River flood water. Since the high turbidity was only a seasonal and short term problem, the general applicability of pebble matrix filters for NOM removal was also investigated. A 1.0 m deep bed of pebbles (the matrix) partly in-filled with either sand or crushed glass was tested, upon which was situated a layer of granular activated carbon (GAC). Turbidity was measured as a surrogate for suspended solids (SS), whereas, total organic carbon (TOC) and UV Absorbance at 254 nm were measured as surrogate parameters for NOM. Experiments using natural flood water showed that without the addition of any chemical coagulants, PMF columns achieved at least 50% turbidity reduction when the source water contained moderate hardness levels. For harder water samples, above 85% turbidity reduction was obtained. The ability to remove 50% turbidity without chemical coagulants may represent significant cost savings to water treatment plants and added environmental benefits accrue due to less sludge formation. A TOC reduction of 35-47% and UV-254 nm reduction of 24-38% was also observed. In addition to turbidity removal during flood periods, the ability to remove NOM using the pebble matrix filter throughout the year may have the benefit of reducing disinfection by-products (DBP) formation potential and coagulant demand at water treatment plants. Final head losses were remarkably low, reaching only 11 cm at a filtration velocity of 0.70 m/h.

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.

Ion exchange of sodium chloride and sodium bicarbonate solutions using strong acid cation resins in relation to coal seam water treatment

Coal seam gas production has resulted in the production of large volumes of associated water which contains dissolved salts dominated by sodium chloride and sodium bicarbonate. Ion exchange using synthetic resins has been proposed as a method for desalination of coal seam water to make it suitable for various beneficial reuse options. This study investigated the behaviour of solutions of sodium chloride and sodium bicarbonate with respect to exchange with Lanxess S108H strong acid cation (SAC) resin. Equilibrium isotherms were created for solutions of NaCl and NaHCO3 and an actual sample of coal seam water from the Surat Basin in southern Queensland. The exchange of sodium ions arising from sodium bicarbonate was found to be considerably more favourable than exchange of sodium ions from sodium chloride solutions. This latter behaviour was attributed to the secondary decomposition of bicarbonate species under acidic conditions which resulted in the evolution of carbon dioxide and formation of water. The isotherm profiles could not be satisfactorily fitted by a single isotherm model such as the Langmuir expression. Instead, two Langmuir equations had to be simultaneously applied in order to fit the sections of the isotherm attributable to sodium ion exchange from sodium bicarbonate and sodium chloride. The shape of the isotherm profile was dependent upon the ratio of sodium chloride to sodium bicarbonate in solution and there was a high degree of correlation between simulated and actual coal seam water solutions.

Behaviour of natural zeolites used for the treatment of simulated and actual coal seam gas water

Coal seam gas operations produce significant quantities of associated water which often require demineralization. Ion exchange with natural zeolites has been proposed as a possible approach. The interaction of natural zeolites with solutions of sodium chloride and sodium bicarbonate in addition to coal seam gas water is not clear. Hence, we investigated ion exchange kinetics, equilibrium, and column behaviour of an Australian natural zeolite. Kinetic tests suggested that the pseudo first order equation best simulated the data. Intraparticle diffusion was part of the rate limiting step and more than one diffusion process controlled the overall rate of sodium ion uptake. Using a constant mass of zeolite and variable concentration of either sodium chloride or sodium bicarbonate resulted in a convex isotherm which was fitted by a Langmuir model. However, using a variable mass of zeolite and constant concentration of sodium ions revealed that the exchange of sodium ions with the zeolite surface sites was in fact unfavourable. Sodium ion exchange from bicarbonate solutions (10.3 g Na/kg zeolite) was preferred relative to exchange from sodium chloride solutions (6.4 g Na/kg zeolite). The formation of calcium carbonate species was proposed to explain the observed behaviour. Column studies of coal seam gas water showed that natural zeolite had limited ability to reduce the concentration of sodium ions (loading 2.1 g Na/kg zeolite) with rapid breakthrough observed. It was concluded that natural zeolites may not be suitable for the removal of cations from coal seam gas water without improvement of their physical properties.

Changes in cannabis use among psychotic clients without specialised substance use treatment

The need to address substance use among people with psychosis has been well established. However, treatment studies targeting substance use in this population have reported mixed results. Substance users with psychosis in no or minimal treatment control groups achieve similar reductions in substance use compared to those in more active substance use treatment, suggesting a role for natural recovery from substance use. This meta-analysis aims to quantify the amount of natural recovery from substance use within control groups of treatment studies containing samples of psychotic substance users, with a particular focus on changes in cannabis use. A systematic search was conducted to identify substance use treatment studies. Meta-analyses were performed to quantify reductions in the frequency of substance use in the past 30 days. Significant but modest reductions (mean reduction of 0.3–0.4 SD across the time points) in the frequency of substance use were found at 6 to 24 months follow up. The current study is the first to quantify changes in substance use in samples enrolled in no treatment or minimal treatment control conditions. These findings highlight the potential role of natural recovery from substance use among individuals with psychosis, although they do not rule out effects of regression to the mean. Additionally, the results provide a baseline from which to estimate likely changes or needed effects sizes in intervention studies. Future research is required to identify the processes underpinning these changes, in order to identify strategies that may better support self-management of substance use in people with psychosis.

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.