A composite serum biomarker index for the diagnosis of systemic sclerosis interstitial lung disease: a multicentre, observational, cohort study

OBJECTIVE: In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk-stratification of SSc-associated interstitial lung disease (SSc-ILD). METHODS: Twenty-eight biomarkers were analysed in 640 participants: 259 with SSc-ILD and 179 SSc-controls without ILD (Australian Scleroderma Cohort Study), 172 idiopathic pulmonary fibrosis (IPF)-controls (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. Performance of the index to identify ILD, and specifically SSc-ILD, and its association with lung function, radiological extent, health-related quality of life (HRQoL) were evaluated in derivation and validation cohorts. Biomarkers to distinguish SSc-ILD from IPF-controls were identified. RESULTS: A composite biomarker index, comprising SP-D, Ca15-3 and ICAM-1, was strongly associated with SSc-ILD diagnosis, independent of age, sex, smoking and lung function (index=3: pooled adjusted OR 12.72, 95%CI 4.59-35.21, p<0.001). The composite index strengthened the performance of individual biomarkers for SSc-ILD identification. In SSc patients, a higher index was associated with worse baseline disease severity (index=3 relative to index=0: adjusted absolute change in FVC% - 17.84% and DLCO% - 20.16%, both p<0.001). CONCLUSION: A composite serum biomarker index, comprising SP-D, Ca15-3 and ICAM-1 may improve the identification and risk-stratification of ILD in SSc patients at baseline

The effectiveness of metal on metal hip resurfacing: a systematic review of the available evidence published before 2002

BACKGROUND: Conventional total hip replacement (THR) may be felt to carry too high a risk of failure over a patient's lifetime, especially in young people. There is increasing interest in metal on metal hip resurfacing arthroplasty (MoM) as this offers a bone-conserving option for treating those patients who are not considered eligible for THR. We aim to evaluate the effectiveness of MoM for treatment of hip disease, and compare it with alternative treatments for hip disease offered within the UK. METHODS: A systematic review was carried out to identify the relevant literature on MoM published before 2002. As watchful waiting and total hip replacement are alternative methods commonly used to alleviate the symptoms of degenerative joint disease of the hip, we compared MoM with these. RESULTS: The data on the effectiveness of MoM are scarce, as it is a relatively new technique and at present only short-term results are available. CONCLUSION: It is not possible to make any firm conclusions about the effectiveness of MoM based on these early results. While the short-term results are promising, it is unclear if such results would be replicated in more rigorous studies, and what the long-term performance might be. Further research is needed which ideally should involve long-term randomised comparisons of MoM with alternative approaches to the clinical management of hip disease

The NKF-NUS hemodialysis trial protocol - a randomized controlled trial to determine the effectiveness of a self management intervention for hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Poor adherence to treatment is common in patients on hemodialysis which may increase risk for poor clinical outcomes and mortality. Self management interventions have been shown to be effective in improving compliance in other chronic populations. The aim of this trial is to evaluate the effectiveness of a recently developed group based self management intervention for hemodialysis patients compared to standard care.</p> <p>Methods/Design</p> <p>This is a multicentre parallel arm block randomized controlled trial (RCT) of a four session group self management intervention for hemodialysis patients delivered by health care professionals compared to standard care. A total of 176 consenting adults maintained on hemodialysis for a minimum of 6 months will be randomized to receive the self management intervention or standard care. Primary outcomes are biochemical markers of clinical status and adherence. Secondary outcomes include general health related quality of life, disease-specific quality of life, mood, self efficacy and self-reported adherence. Outcomes will be measured at baseline, immediately post-intervention and at 3 and 9 months post-intervention by an independent assessor and analysed on intention to treat principles with linear mixed-effects models across all time points. A qualitative component will examine which aspects of program participants found particularly useful and any barriers to change.</p> <p>Discussion</p> <p>The NKF-NUS intervention builds upon previous research emphasizing the importance of empowering patients in taking control of their treatment management. The trial design addresses weaknesses of previous research by use of an adequate sample size to detect clinically significant changes in biochemical markers, recruitment of a sufficiently large representative sample, a theory based intervention and careful assessment of both clinical and psychological endpoints at various follow up points. Inclusion of multiple dependent variables allows us to assess the broader impact on the intervention including both hard end points as well as patient reported outcomes. This program, if found to be effective, has the potential to be implemented within the existing renal services delivery model in Singapore, particularly as this is being delivered by health care professionals already working with hemodialysis patients in these settings who are specifically trained in facilitating self management in renal patients.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRTN31434033">ISRTN31434033</a></p

Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD): study protocol for establishing a core outcome set in polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life threatening inherited kidney disease and is responsible for 5-10% of cases of end-stage kidney disease (ESKD). Cystic kidneys may enlarge up to 20 times the weight of a normal kidney due to the growth of renal cysts, and patients with ADPKD have an increased risk of morbidity, premature mortality, and other life-time complications including renal and hepatic cyst and urinary tract infection, intracranial aneurysm, diverticulosis, and kidney pain which impair quality of life. Despite some therapeutic advances and the growing number of clinical trials in ADPKD, the outcomes that are relevant to patients and clinicians, such as symptoms and quality of life, are infrequently and inconsistently reported. This potentially limits the contribution of trials to inform evidence-based decision-making. The Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) project aims to establish a consensus-based set of core outcomes for trials in PKD (with an initial focus on ADPKD but inclusive of all stages) that patients and health professionals identify as critically important. METHODS: The five phases of SONG-PKD are: a systematic review to identify outcomes that have been reported in existing PKD trials; focus groups with nominal group technique with patients and caregivers to identify, rank, and describe reasons for their choices; qualitative stakeholder interviews with health professionals to elicit individual values and perspectives on outcomes for trials involving patients with PKD; an international three-round Delphi survey with all stakeholder groups (including patients, caregivers, healthcare providers, policy makers, researchers, and industry) to gain consensus on critically important core outcome domains; and a consensus workshop to review and establish a set of core outcome domains and measures for trials in PKD. DISCUSSION: The SONG-PKD core outcome set is aimed at improving the consistency and completeness of outcome reporting across ADPKD trials, leading to improvements in the reliability and relevance of trial-based evidence to inform decisions about treatment and ultimately improve the care and outcomes for people with ADPKD

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Factors associated with FEV1 decline in cystic fibrosis : analysis of the ECFS patient registry

Pulmonary insufficiency is the main cause of death in cystic fibrosis (CF). We analysed forced expiratory volume in 1 s (FEV1) data of 14 732 patients registered in the European Cystic Fibrosis Society Patient Registry (ECFSPR) database in 2007. We used linear and logistic regressions to investigate associations between FEV1 % predicted and clinical outcomes. Body mass index (BMI), chronic infection by Pseudomonas aeruginosa, pancreatic status and CF-related diabetes (CFRD) showed a statistically significant (all p<0.0001) and clinically relevant effect on FEV1 % pred after adjusting for age. Patients with a lower BMI experience a six-fold increased odds ratio (95% CI 5.0-7.3) of having severe lung disease (FEV1 <40% pred) compared to patients with normal BMI. Being chronically infected with P. aeruginosa increases the odds ratio of severe lung disease by 2.4 (95% CI 2.0-2.7), and patients with pancreatic insufficiency experience a 2.0-fold increased odds ratio (95% CI 1.6-2.5) of severe lung disease compared to pancreatic sufficient patients. Patients with CFRD have a 1.8-fold increased odds ratio (95% CI 1.6-2.2) compared to patients not affected. These potential risk factors for pulmonary disease in patients with CF are to some degree preventable or treatable. We emphasise the importance of their early identification through frequent routine tests, the implementation of infection control measures, and a timely initiation of relevant therapies