Australia New Zealand Clinical Trials Registry Research Articles

Use of a decision support tool and quick start onboarding tool in individuals with type 1 diabetes using advanced automated insulin delivery: a single-arm multi-phase intervention study

BackgroundMultiple clinician adjustable parameters impact upon glycemia in people with type 1 diabetes (T1D) using Medtronic Mini Med 780G (MM780G) AHCL. These include glucose targets, carbohydrate ratios (CR), and active insulin time (AIT). Algorithm-based decision support advising upon potential settings adjustments may enhance clinical decision-making.MethodsSingle-arm, two-phase exploratory study developing decision support to commence and sustain AHCL. Participants commenced investigational MM780G, then 8 weeks Phase 1-initial optimization tool evaluation, involving algorithm-based decision support with weekly AIT and CR recommendations. Clinicians approved or rejected CR and AIT recommendations based on perceived safety per protocol. Co-design resulted in a refined algorithm evaluated in a further identically configured Phase 2. Phase 2 participants also transitioned to commercial MM780G following “Quick Start” (algorithm-derived tool determining initial AHCL settings using daily insulin dose and weight). We assessed efficacy, safety, and acceptability of decision support using glycemic metrics, and the proportion of accepted CR and AIT settings per phase.ResultsFifty three participants commenced Phase 1 (mean age 24.4; Hba1c 61.5mmol/7.7%). The proportion of CR and AIT accepted by clinicians increased between Phases 1 and 2 respectively: CR 89.2% vs. 98.6%, p < 0.01; AIT 95.2% vs. 99.3%, p < 0.01. Between Phases, mean glucose percentage time < 3.9mmol (< 70mg/dl) reduced (2.1% vs. 1.4%, p = 0.04); change in mean TIR 3.9-10mmol/L (70-180mg/dl) was not statistically significant: 72.9% ± 7.8 and 73.5% ± 8.6. Quick start resulted in stable TIR, and glycemic metrics compared to international guidelines.ConclusionThe co-designed decision support tools were able to deliver safe and effective therapy. They can potentially reduce the burden of diabetes management related decision making for both health care practitioners and patients.Trial registrationProspectively registered with Australia/New Zealand Clinical Trials Registry(ANZCTR) on 30th March 2021 as study ACTRN12621000360819.

Passive sensing data predicts stress in university students: a supervised machine learning method for digital phenotyping.

University students are particularly susceptible to developing high levels of stress, which occur when environmental demands outweigh an individual's ability to cope. The growing advent of mental health smartphone apps has led to a surge in use by university students seeking ways to help them cope with stress. Use of these apps has afforded researchers the unique ability to collect extensive amounts of passive sensing data including GPS and step detection. Despite this, little is known about the relationship between passive sensing data and stress. Further, there are no established methodologies or tools to predict stress from passive sensing data in this group. In this study, we establish a clear machine learning-based methodological pipeline for processing passive sensing data and extracting features that may be relevant in the context of mental health. We then use this methodology to determine the relationship between passive sensing data and stress in university students. In doing so, we offer the first proof-of-principle data for the utility of our methodological pipeline and highlight that passive sensing data can indeed digitally phenotype stress in university students. Australia New Zealand Clinical Trials Registry (ANZCTR), identifier ACTRN12621001223820.

Stroke Riskometer Application (SRA™) influence on lifestyle changes of home bound familial Malaysian stroke caregivers: a randomised controlled trial in a primary care based longer term stroke care facility

BackgroundIn countries where access to Specialist stroke care services are limited, primary care physicians often manage stroke patients and the caregiving family members. This study aimed to evaluate the impact of Stroke Riskometer Application (SRA™) on promoting healthier lifestyles among familial stroke caregivers for primary prevention.MethodsA parallel, open-label, 2-arm prospective, pilot randomised controlled trial was conducted at a long-term stroke service at a university based primary care clinic. All stroke caregivers aged ≥ 18 years, proficient in English or Malay and smartphone operation were invited. From 147 eligible caregivers, 76 participants were randomised to either SRA™ intervention or conventional care group (CCG) after receiving standard health counselling. The intervention group had additional SRA™ installed on their smartphones, which enabled self-monitoring of modifiable and non-modifiable stroke risk factors. The Stroke Riskometer app (SRATM) and Life's Simple 7 (LS7) questionnaires assessed stroke risk and lifestyle practices. Changes in clinical profile, lifestyle practices and calculated stroke risk were analysed at baseline and 3 months.The trial was registered in the Australia-New Zealand Clinical Trial Registry, ACTRN12618002050235.ResultsThe demographic and clinical characteristics of the intervention and control group study participants were comparable. Better improvement in LS7 scores were noted in the SRA™ arm compared to CCG at 3 months: Median difference (95% CI) = 0.88 (1.68–0.08), p = 0.03. However, both groups did not show significant changes in median stroke risk and relative risk scores at 5-, 10-years (Stroke risk 5-years: Median difference (95% CI) = 0.53 (0.15–1.21), p = 0.13, 10-years: Median difference (95% CI) = 0.81 (0.53–2.15), p = 0.23; Relative risk 5-years: Median difference (95% CI) = 0.84 (0.29–1.97), p = 0.14, Relative risk 10-years: Median difference (95% CI) = 0.58 (0.36–1.52), p = 0.23).ConclusionSRA™ is a useful tool for familial stroke caregivers to make lifestyle changes, although it did not reduce personal or relative stroke risk after 3 months usage.Trial registrationNo: ACTRN12618002050235 (Registration Date: 21st December 2018).

Effects of Aromatherapy Through Inhalation on Work Stress and Job Satisfaction Among Health Professionals.

The aim of this study was to examine the effects of lavender oil inhalation on work stress and job satisfaction among health professionals. This randomized, experimental study involved 108 health professionals, of whom 36 were randomized into the intervention group, 35 into the placebo group, and 37 into the control group. The intervention was performed during work shifts of the intervention group (8 hours a day during a 5-day period). The intervention group was exposed to lavender oil inhalation through a diffuser and the placebo group was exposed to inhalation of distilled water containing light yellow food dye, but the control group did not receive anything. Data were collected with General Characteristics Form, The Swedish Demand-Control-Support Questionnaire, and The Minnesota Satisfaction Scale. The study was also registered at the Australia-New Zealand Clinical Trials Registry (ACTRN12621000239864). Before the intervention, no significant difference was found in work stress and job satisfaction levels between the intervention, placebo, and control groups. After the intervention, the intervention group had a significantly lower work stress level and a significantly higher job satisfaction level than the placebo and control groups (P < .05). Lavender oil inhalation can decrease work stress and improve job satisfaction.

The impact of nursing staff education on diabetes inpatient glucose management: a pilot cluster randomised controlled trial

BackgroundAn increasing number of patients in hospital have diabetes, with most of them cared for by non-specialist staff. The effect of diabetes education for staff on patient outcomes, as well as the most effective method of staff education is unclear. Therefore, the aim of this study was to compare diabetes outcomes in medical wards where nursing staff were offered one face-to-face (F2F) session followed by access to online education (online), F2F education only, or standard care (control).MethodsWe conducted a pilot cluster randomised controlled trial involving 16-weeks baseline/rollout followed by a 28-week post-intervention period across three medical wards (clusters) in a Sydney Teaching Hospital. The online ward provided an online competency-based diabetes education program and 1-h F2F teaching from a diabetes nurse educator (DNE), the F2F ward provided four separate 1-h teaching sessions by a DNE, with no additional sessions in the control ward. The primary outcome was length of stay (LOS); secondary outcomes included good diabetes days (GDD), hypoglycaemia and medication errors. Poisson and binary logistic regression were used to compare clusters.ResultsStaff attendance/completion of ≥ 2 topics was greater with online than F2F education [39/48 (81%) vs 10/33 (30%); p < 0.001]. Among the 827/881 patients, there was no difference in LOS change between online [Median(IQR) 5(2–8) to 4(2–7) days], F2F [7(4–14) to 5(3–13) days] or control wards [5(3–9) to 5(3–7) days]. GDD improved only in the online ward 4.7(2.7–7.0) to 6.0(2.3–7.0) days; p = 0.038. Total patients with hypoglycaemia and appropriately treated hypoglycaemia increased in the online ward.ConclusionsThe inclusion of online education increased diabetes training uptake among nursing staff. GDD and appropriate hypoglycaemia management increased in the online education wards.Trial registrationProspectively registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) on 24/05/2017: ACTRN12617000762358.

Protocol for SARS-CoV-2 post-vaccine surveillance study in Australian adults and children with cancer: an observational study of safety and serological and immunological response to SARS-CoV-2 vaccination (SerOzNET)

BackgroundCancer is associated with excess morbidity and mortality from coronavirus disease 2019 (COVID-19) following infection by the novel pandemic coronavirus SARS-CoV-2. Vaccinations against SARS-CoV-2 have been rapidly developed and proved highly effective in reducing the incidence of severe COVID-19 in clinical trials of healthy populations. However, patients with cancer were excluded from pivotal clinical trials. Early data suggest that vaccine response is less robust in patients with immunosuppressive conditions or treatments, while toxicity and acceptability of COVID-19 vaccines in the cancer population is unknown. Unanswered questions remain about the impact of various cancer characteristics (such as treatment modality and degree of immunosuppression) on serological response to and safety of COVID-19 vaccinations. Furthermore, as the virus and disease manifestations evolve, ongoing data is required to address the impact of new variants.MethodsSerOzNET is a prospective observational study of adults and children with cancer undergoing routine SARS-CoV-2 vaccination in Australia. Peripheral blood will be collected and processed at five timepoints (one pre-vaccination and four post-vaccination) for analysis of serologic responses to vaccine and exploration of T-cell immune correlates. Cohorts include: solid organ cancer (SOC) or haematological malignancy (HM) patients currently receiving (1) chemotherapy, (2) immune checkpoint inhibitors (3) hormonal or targeted therapy; (4) patients who completed chemotherapy within 6–12 months of vaccination; (5) HM patients with conditions associated with hypogammaglobulinaemia or immunocompromise; (6) SOC or HM patients with allergy to PEG or polysorbate 80. Data from healthy controls already enrolled on several parallel studies with comparable time points will be used for comparison. For children, patients with current or prior cancer who have not received recent systemic therapy will act as controls. Standardised scales for quality-of-life assessment, patient-reported toxicity and vaccine hesitancy will be obtained.DiscussionThe SerOzNET study was commenced in June 2021 to prospectively study immune correlates of vaccination in specific cancer cohorts. The high proportion of the Australian population naïve to COVID-19 infection and vaccination at study commencement has allowed a unique window of opportunity to study vaccine-related immunity. Quality of life and patient-reported adverse events have not yet been reported in detail post-vaccination for cancer patients.Trial registration This trial is registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001004853. Submitted for registration 25 June 2021. Registered 30 July 2021 (Retrospectively registered). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382281&isReview=true

Prolactin Level and Breastmilk Production among Mothers of Low-Birth-Weight Infants Admitted to Level II Neonatal Intensive Care Unit

Background. Kangaroo mother care (KMC) has been proven by several studies to promote breastfeeding, but many of the studies focus on the success of exclusive breastfeeding, and less on its galactogenic effects.&#x0D; Objective. We aim to determine the maternal serum prolactin levels and breastmilk volume of mothers who rendered KMC to their infants.&#x0D; Materials and Methods. This is a randomized controlled, open-labeled, interventional study in the Neonatal Intensive Care Unit of a tertiary government hospital. Infants weighing &lt; 2000 grams admitted in NICU Level II, together with medically stable mothers and no contraindication for breastfeeding were simultaneously enrolled. Primary outcome measures were maternal serum prolactin levels and expressed milk volume on day 3 and day 7 postpartum. Two-sample t-test was used to compare groups, and paired t-test to compare within groups. Tests were two-tailed, with a p-value of &lt; 0.05 considered statistically significant.&#x0D; Trial Registration. Australia-New Zealand Clinical Trial Registry ID ACTRN12614000218695&#x0D; Results. Fifty mother-infant dyads were equally allocated into KMC and control groups (p &lt; 0.001). There was significantly larger milk volume on the third day (29.6 ± 27.8 mL vs 16.3 ± 26.1 mL; p &lt; 0.001) and seventh post-partum day (72.4 ± 62.3 mL vs 47.3 ± 43.8 mL; p &lt; 0.000). There were increased serum prolactin levels compatible with post-partum state. The increase was more evident in the KMC (5244 ± 2702 mIU/L, on the 3rd postpartum day versus 4969 ± 2426 mIU/L, on the 7th postpartum day, p = 0.996) compared to control group (4129 ± 2485 mIU/L on the 3rd postpartum day versus 3705 ± 2731 mIU/L on the 7th postpartum day, p = 0.301).&#x0D; Conclusion. We noted a significantly larger milk volume in the KMC group. There was also a greater increase in the prolactin levels in the KMC group, but this did not reach statistical significance. Further studies should be done to determine mechanism of galactogenesis through KMC.

Influence of serum inflammatory cytokines on cytochrome P450 drug metabolising activity during breast cancer chemotherapy: a patient feasibility study

Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exercise are associated with better and worse outcomes, respectively, and it is known that both impact the systemic cytokine milieu. Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many chemotherapy agents, and CYP enzyme activity has been shown to be modified by inflammatory cytokines in vitro and in vivo. Cytokine-associated changes in CYP metabolism may alter chemotherapy exposure, potentially affecting treatment response and patient survival. Therefore, better understanding of these biological relationships is required. This exploratory single arm open label trial investigated changes in in vivo CYP activity in twelve women treated for stage II or III breast cancer, and demonstrated for the first time the feasibility and safety of utilising the Inje phenotyping cocktail to measure CYP activity in cancer patients receiving chemotherapy. Relative CYP activity varied between participants, particularly for CYP2C9 and CYP2D6, and changes in serum concentrations of the inflammatory cytokine monocyte chemoattractant protein 1 inversely correlated to CYP3A4 activity during chemotherapy. Future use of phenotyping cocktails in a clinical oncology setting may help guide drug dosing and improve chemotherapy outcomes.Clinical Trial Registration: Trial was retrospectively registered to the Australia New Zealand Clinical Trial Registry (ANZCTR). ACTRN12620000832976, 21 Aug 2020, https://www.anzctr.org.au/ACTRN12620000832976.aspx.

Safety and feasibility of apheresis to harvest and concentrate parasites from subjects with induced blood stage Plasmodium vivax infection

BackgroundIn the absence of a method to culture Plasmodium vivax, the only way to source parasites is ex vivo. This hampers many aspects of P. vivax research. This study aimed to assess the safety of apheresis, a method for selective removal of specific components of blood as a means of extracting and concentrating P. vivax parasites.MethodsAn iterative approach was employed across four non-immune healthy human subjects in single subject cohorts. All four subjects were inoculated with ~ 564 blood stage P. vivax (HMP013-Pv) and subjected to apheresis 10 to 11 days later. Blood samples collected during apheresis (haematocrit layers 0.5% to 11%) were tested for the presence and concentration of P. vivax by microscopy, flow cytometry, 18S rDNA qPCR for total parasites, and pvs25 qRT-PCR for female gametocyte transcripts. Safety was determined by monitoring adverse events. Malaria transmission to mosquitoes was assessed by membrane feeding assays.ResultsThere were no serious adverse events and no significant safety concerns. Apheresis concentrated asexual parasites by up to 4.9-fold (range: 0.9–4.9-fold) and gametocytes by up to 1.45-fold (range: 0.38–1.45-fold) compared to pre-apheresis densities. No single haematocrit layer contained > 40% of all the recovered P. vivax asexual parasites. Ex vivo concentration of parasites by Percoll gradient centrifugation of whole blood achieved greater concentration of gametocytes than apheresis. Mosquito transmission was enhanced by up to fivefold in a single apheresis sample compared to pre-apheresis.ConclusionThe modest level of parasite concentration suggests that the use of apheresis may not be an ideal method for harvesting P. vivax.Trial Registration Australia New Zealand Clinical Trials Registry (ANZCTR) Trial ID: ACTRN12617001502325 registered on 19th October 2017. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373812.

Flash glucose monitoring for the safe use of a 2-day intermittent energy restriction in patients with type 2 diabetes at risk of hypoglycaemia: An exploratory study

AimsTwo medication change protocols were tested, both based on haemoglobin A1c (HbA1c), with one protocol also accounting for hypoglycaemic events. The aim was to compare the two protocols during intermittent energy restriction (5:2 diet). MethodsForty-two adults with type 2 diabetes (HbA1c ≥ 7% [53 mmol/mol], BMI of ≥27 kg/m2) treated with sulphonylureas and/or insulin were recruited and randomised 1:1 to fixed or adjusted medication protocols. Participants experiencing hypoglycaemia during a 2-week usual diet period then followed the 5:2 diet for 2 weeks (2 non-consecutive very-low-calorie days [500–600 kcal] and 5 habitual eating days/week), following the allocated medication protocol. The primary outcome was to determine if the adjusted protocol was superior to the fixed protocol at reducing hypoglycaemic events during the 5:2 diet. Flash glucose monitoring was used throughout to detect hypoglycaemia. ResultsThere was a significant difference in change in the number of hypoglycaemic events between fixed and adjusted protocols (−1.0 vs. −3.5; P = 0.04). Over 60% of participants on the adjusted protocol had no hypoglycaemic events. ConclusionsThis pilot study demonstrates the importance of assessing the risk of hypoglycaemia before starting a 5:2 diet and that the adjusted medication protocol is likely the best option for patients at risk. Clinical trial registryThis study has been registered with the Australia New Zealand Clinical Trial Registry (ANZCTR) www.anzctr.org.au and given the registration number ACTRN12617000512325.

Early Initiation of Breastfeeding Protects Against Early-Onset Sepsis Among Newborns: Evidence from Rural Bangladesh

Background: In Bangladesh, neonatal sepsis is the cause of 24% of neonatal deaths, over 65% of which occur in the early-newborn stage (0-7 days). Only 50% of women initiate breastfeeding their newborn within 1 hour of birth. The mechanism by which early initiation of breastfeeding reduces neonatal deaths is unclear, although the most likely pathway is by decreasing neonatal sepsis. This study explores the effect of breastfeeding initiation time on early-onset newborn sepsis. Methods: We used data from a large community-based trial in Bangladesh where we enrolled pregnant women from 2013-2015 covering 30,646 newborns. Syndromic sepsis was defined using newborn danger signs reported by “The Young-Infants Clinical Science Study Group.” We categorized the timing of initiation of breastfeeding as within 1 hour, 1-24 hours, 24-48 hours, ≥48 hours of birth, and never breastfed. The analysis includes descriptive statistics, risk attribution, and binomial logistic-regression while adjusting for clustering effects of the trial design, and maternal and infant characteristics. Findings: 29,873 live-births had information on breastfeeding initiation among whom 4,437 (14·8%) neonates had signs of sepsis by the 7th day after birth. Two-thirds of the newborns [66·7%, (n=19,914)] had breastfeeding initiated within 1hr of birth. The mean time to initiation was 3·8 hours (±16·6 hours), and by the end of 48 hours, all but 5·7% of neonates were breastfed. The proportion of children with syndromic sepsis increased as the initiation of breastfeeding was delayed from 1 hour (12·0%), 24 hours (15·7%), 48 hours (27·7%), to more than 48 hours (36·7%) after birth. It would be possible to avert 15·9%, 10·6% and 8·5% of early-onset sepsis cases if all children initiated breastfeeding within 1, 24 or 48 hours of birth respectively. The odds of having sepsis is significantly higher among late initiators. Children who initiated after 48 hours (OR 4·13, 95% CI 3·48-4·89) and children who never initiated (OR 4·77, 95% CI 3·52-6·47) had the highest odds of having signs of sepsis. Interpretation: Our findings indicate that the timing of initiation of breastfeeding, especially within the first hour of birth, has a significant protective effect on early-onset sepsis among newborns. Community-based interventions to promote early initiation of breastfeeding should be tailored to suit the needs of populations where newborns are delivered at home by unskilled attendants, the rate of LBW is high, and post-natal care is limited. Clinical Trial Number: Australia New Zealand Clinical Trials Registry (ANZCTR): The registration ID is ACTRN12612000588897. Funding Statement: National Health and Medical Research Council [NHMRC] (of Australia) funded this study (#1026864). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The Ethical Review Committee (ERC) of the icddr,b, and the Human Research Ethics Committee (HREC) of the University of Sydney have granted ethics approval for the parent study. We obtained written informed consent, from pregnant women during enrollment into the study, which provided full disclosure regarding the study.

POWIFF- Prospective study of wrist internal fixation of fracture: A protocol for a single centre, superiority, randomised controlled trial to study the efficacy of the VRP (2.0) distal radius plate (Austofix) versus the VA-LCP (Depuy-Synthes) for distal radius fractures

BackgroundDistal radial fractures are one of the most common orthopaedic cases that present to the A&E department. Surgical intervention is warranted in displaced intraarticular fractures and fractures with more than the recommended angulation or shortening, and is most commonly treated with volarly placed fixed angle locking plates. The aim of this study is to determine and compare the efficacy of two different plates for surgical treatment of distal radius fractures. The VRP 2.0 is a new plate produced by the Austofix company and this system will be compared against the VA-LP (Variable angle-locking plate) produced by Depuy-Synthes which has been used as the standard treatment device.Methods and DesignPatients between the ages of 18 and 80 presenting to the Royal Adelaide Hospital with isolated closed distal radial fractures will be invited to participate in this study. A total of 200 patients are required to provide 90% statistical power at a 5% alpha level to detect a difference of 11.5 points on the PRWE (Patient rated Wrist evaluation) score. The primary outcome measure will be the PRWE score while the secondary outcome measures will include the DASH score, EQ5D score, clinical range of movements, grip strength as well as patient perceived return of function at the wrist and time to resumption to work. These will be measured at 6 weeks, 3 months and 12 months. Radiographic indices including the radial tilt, length, volar inclination and plate prominence will also be measured. Complications will be recorded up to 12 months. Post hoc comparisons will be done using paired t tests. An intention to treat and a per protocol analysis will be done to compare the 2 groups.DiscussionDistal radial fractures are increasingly being treated by internal fixation using volar locking plates. However, there is no prospective study to date comparing one plate against another in terms of outcome and complications. This study could provide more information about the best way to treat these injuries surgically.Trial registrationThe trial is registered with the Australia New Zealand Clinical Trials Registry (ANZCTR). Trial registration date-17/11/2016. Trial registration number-ACTRN12616001590459.

An Objective Short Sleep Insomnia Disorder Subtype Is Associated With Reduced Brain Metabolite Concentrations In Vivo: A Preliminary Magnetic Resonance Spectroscopy Assessment.

To evaluate brain metabolites in objective insomnia subtypes defined from polysomnography (PSG): insomnia with short sleep duration (I-SSD) and insomnia with normal sleep duration (I-NSD), relative to good sleeping controls (GSCs). PSG empirically grouped insomnia patients into I-SSD (n = 12: mean [SD] total sleep time [TST] = 294.7 minutes [30.5]) or I-NSD (n = 19: TST = 394.4 minutes [34.9]). 1H magnetic resonance spectroscopy (MRS) acquired in the left occipital cortex (LOCC), left prefrontal cortex, and anterior cingulate cortex was used to determine levels of creatine, aspartate, glutamate, and glutamine (referenced to water). Glutathione, glycerophosphocholine, lactate, myoinositol, and N-acetylaspartate measurements were also obtained. Sixteen GSCs were included for comparison. Multivariate analysis of variance was used to evaluate differences in creatine, aspartate, glutamate, and glutamine. Aspartate and glutamine concentrations were reduced in the LOCC in I-SSD compared with I-NSD (both p < .05, d = .80-.99). Creatine displayed a nonsignificant mean reduction in I-SSD compared with I-NSD (p = .05, d = .58). Glutamine was reduced in I-SSD compared with controls (p < .05, d = .93). There were no differences in metabolites between all (I-SSD and I-NSD) insomnia patients and controls. In patients with insomnia, LOCC glutamine concentrations were found to be positively correlated with TST (r = .43, p < .05) and negatively correlated with wake-time after sleep onset (r = -.40, p < .05). Results indicate that I-SSD is associated with reduced brain metabolites in the LOCC compared with I-NSD and control concentrations of aspartate, glutamine, and creatine. Insomnia MRS imaging sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000050853. 12612000050853.

The organisational value of diagnostic strategies using high-sensitivity troponin for patients with possible acute coronary syndromes: a trial-based cost-effectiveness analysis

ObjectivesTo evaluate hospital-specific health economic implications of different protocols using high-sensitivity troponin I for the assessment of patients with chest pain.DesignA cost prediction model and an economic microsimulation were developed...

Positioning and spinal bracing for pain relief in metastatic spinal cord compression in adults.

This is an updated version of the original Cochrane review published in Issue 3 (Lee 2012) on patient positioning (mobilisation) and bracing for pain relief and spinal stability in adults with metastatic spinal cord compression.Many patients with metastatic spinal cord compression (MSCC) have spinal instability, but their clinician has determined that due to their advanced disease they are unsuitable for surgical internal fixation. Mobilising may be hazardous in the presence of spinal instability as further vertebral collapse can occur. Current guidance on positioning (whether a patient should be managed with bed rest or allowed to mobilise) and whether spinal bracing is helpful, is contradictory. To investigate the correct positioning and examine the effects of spinal bracing to relieve pain or to prevent further vertebral collapse in patients with MSCC. For this update, we searched for relevant studies from February 2012 to 31 March 2015. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE In Process, EMBASE, AMED, CINAHL, TRIP, SIGN, NICE, UK Clinical Research Network, National Guideline Clearinghouse and PEDro database. We also searched the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov, UK Clinical Trials Gateway (UKCTG), WHO International Clinical Trials Registry Platform (ICTRP) and Australia New Zealand Clinical Trials Registry (ANZCTR).For the original version, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, CANCERLIT, NICE, SIGN, AMED, TRIP, National Guideline Clearinghouse, and PEDro database, in February 2012. We selected randomised controlled trials (RCTs) of adults with MSCC of interventions on positioning (mobilisation) and bracing. Two review authors independently assessed each possible study for inclusion and quality. For the original version of the review, we screened 1611 potentially relevant studies. No studies met the inclusion criteria. Many papers identified the importance of mobilisation, but no RCTs of bed rest versus mobilisation have been undertaken. We identified no RCTs of bracing in MSCC.For this update, we identified 347 potential titles. We screened 300 titles and abstracts after removal of duplicates. We did not identify any additional studies for inclusion. Since publication of the original version of this review, no new studies were found and our conclusions remain unchanged.There is a lack of evidence-based guidance around how to correctly position and when to mobilise patients with MSCC or if spinal bracing is an effective technique for reducing pain or improving quality of life. RCTs are required in this important area.

Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial

AbstractErdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, to whose pathogenesis neoplastic and immune-mediated mechanisms contribute. Mammalian target of rapamycin (mTOR)-inhibitors have antiproliferative and immunosuppressive properties. We tested in this study, the efficacy and safety of the mTOR-inhibitor sirolimus (SRL) plus prednisone (PDN) in patients with ECD. PDN was given initially at 0.75 mg/kg per day, tapered to 5 to 2.5 mg per day by month 6. Target SRL blood levels were 8 to 12 ng/mL. Treatment was continued for at least 24 months in patients who showed disease stabilization or improvement. Ten patients were enrolled; 8 achieved stable disease or objective responses, whereas 2 had disease progression. Responses were mainly observed at the following sites: retroperitoneum in 5/8 patients (62.5%), cardiovascular in 3/4 (75%), bone in 3/9 (33.3%), and central nervous system (CNS) in 1/3 (33.3%). The median follow-up was 29 months (interquartile range, 16.5-74.5); 2 patients died of progressive CNS disease and small-cell lung cancer, respectively. Treatment-related toxicity was mild. Using immunohistochemistry and immunofluorescence on ECD biopsies, we detected expression in foamy histiocytes of the phosphorylated forms of mTOR and of its downstream kinase p70S6K, which indicated mTOR pathway activation. In conclusion, SRL and PDN often induce objective responses or disease stabilization and may represent a valid treatment of ECD. The trial is registered at the Australia-New Zealand Clinical Trial Registry as #ACTRN12613001321730.

Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial

We assessed patient outcomes 90 days after hospital admission for stroke following a multidisciplinary intervention targeting evidence-based management of fever, hyperglycaemia, and swallowing dysfunction in acute stroke units (ASUs). In the Quality in Acute Stroke Care (QASC) study, a single-blind cluster randomised controlled trial, we randomised ASUs (clusters) in New South Wales, Australia, with immediate access to CT and on-site high dependency units, to intervention or control group. Patients were eligible if they spoke English, were aged 18 years or older, had had an ischaemic stroke or intracerebral haemorrhage, and presented within 48 h of onset of symptoms. Intervention ASUs received treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction with multidisciplinary team building workshops to address implementation barriers. Control ASUs received only an abridged version of existing guidelines. We recruited pre-intervention and post-intervention patient cohorts to compare 90-day death or dependency (modified Rankin scale [mRS] ≥2), functional dependency (Barthel index), and SF-36 physical and mental component summary scores. Research assistants, the statistician, and patients were masked to trial groups. All analyses were done by intention to treat. This trial is registered at the Australia New Zealand Clinical Trial Registry (ANZCTR), number ACTRN12608000563369. 19 ASUs were randomly assigned to intervention (n=10) or control (n=9). Of 6564 assessed for eligibility, 1696 patients' data were obtained (687 pre-intervention; 1009 post-intervention). Results showed that, irrespective of stroke severity, intervention ASU patients were significantly less likely to be dead or dependent (mRS ≥2) at 90 days than control ASU patients (236 [42%] of 558 patients in the intervention group vs 259 [58%] of 449 in the control group, p=0·002; number needed to treat 6·4; adjusted absolute difference 15·7% [95% CI 5·8-25·4]). They also had a better SF-36 mean physical component summary score (45·6 [SD 10·2] in the intervention group vs 42·5 [10·5] in the control group, p=0·002; adjusted absolute difference 3·4 [95% CI 1·2-5·5]) but no improvement was recorded in mortality (21 [4%] of 558 in intervention group and 24 [5%] of 451 in the control group, p=0·36), SF-36 mean mental component summary score (49·5 [10·9] in the intervention group vs 49·4 [10·6] in the control group, p=0·69) or functional dependency (Barthel Index ≥60: 487 [92%] of 532 patients vs 380 [90%] of 423 patients; p=0·44). Implementation of multidisciplinary supported evidence-based protocols initiated by nurses for the management of fever, hyperglycaemia, and swallowing dysfunction delivers better patient outcomes after discharge from stroke units. Our findings show the possibility to augment stroke unit care. National Health & Medical Research Council ID 353803, St Vincent's Clinic Foundation, the Curran Foundation, Australian Diabetes Society-Servier, the College of Nursing, and Australian Catholic University.

A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study

Patients with chest pain contribute substantially to emergency department attendances, lengthy hospital stay, and inpatient admissions. A reliable, reproducible, and fast process to identify patients presenting with chest pain who have a low short-term risk of a major adverse cardiac event is needed to facilitate early discharge. We aimed to prospectively validate the safety of a predefined 2-h accelerated diagnostic protocol (ADP) to assess patients presenting to the emergency department with chest pain symptoms suggestive of acute coronary syndrome. This observational study was undertaken in 14 emergency departments in nine countries in the Asia-Pacific region, in patients aged 18 years and older with at least 5 min of chest pain. The ADP included use of a structured pre-test probability scoring method (Thrombolysis in Myocardial Infarction [TIMI] score), electrocardiograph, and point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin. The primary endpoint was major adverse cardiac events within 30 days after initial presentation (including initial hospital attendance). This trial is registered with the Australia-New Zealand Clinical Trials Registry, number ACTRN12609000283279. 3582 consecutive patients were recruited and completed 30-day follow-up. 421 (11.8%) patients had a major adverse cardiac event. The ADP classified 352 (9.8%) patients as low risk and potentially suitable for early discharge. A major adverse cardiac event occurred in three (0.9%) of these patients, giving the ADP a sensitivity of 99.3% (95% CI 97.9-99.8), a negative predictive value of 99.1% (97.3-99.8), and a specificity of 11.0% (10.0-12.2). This novel ADP identifies patients at very low risk of a short-term major adverse cardiac event who might be suitable for early discharge. Such an approach could be used to decrease the overall observation periods and admissions for chest pain. The components needed for the implementation of this strategy are widely available. The ADP has the potential to affect health-service delivery worldwide. Alere Medical (all countries), Queensland Emergency Medicine Research Foundation and National Health and Medical Research Council (Australia), Christchurch Cardio-Endocrine Research Group (New Zealand), Medquest Jaya Global (Indonesia), Science International (Hong Kong), Bio Laboratories Pte (Singapore), National Heart Foundation of New Zealand, and Progressive Group (Taiwan).