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Protocolised non-invasive compared with invasive weaning from mechanical ventilation for adults in intensive care: the Breathe RCT.
No full textBACKGROUND
Invasive mechanical ventilation (IMV) is a life-saving intervention. Following resolution of the condition that necessitated IMV, a spontaneous breathing trial (SBT) is used to determine patient readiness for IMV discontinuation. In patients who fail one or more SBTs, there is uncertainty as to the optimum management strategy.
OBJECTIVE
To evaluate the clinical effectiveness and cost-effectiveness of using non-invasive ventilation (NIV) as an intermediate step in the protocolised weaning of patients from IMV.
DESIGN
Pragmatic, open-label, parallel-group randomised controlled trial, with cost-effectiveness analysis.
SETTING
A total of 51 critical care units across the UK.
PARTICIPANTS
Adult intensive care patients who had received IMV for at least 48 hours, who were categorised as ready to wean from ventilation, and who failed a SBT.
INTERVENTIONS
Control group (invasive weaning): patients continued to receive IMV with daily SBTs. A weaning protocol was used to wean pressure support based on the patient's condition. Intervention group (non-invasive weaning): patients were extubated to NIV. A weaning protocol was used to wean inspiratory positive airway pressure, based on the patient's condition.
MAIN OUTCOME MEASURES
The primary outcome measure was time to liberation from ventilation. Secondary outcome measures included mortality, duration of IMV, proportion of patients receiving antibiotics for a presumed respiratory infection and health-related quality of life.
RESULTS
A total of 364 patients (invasive weaning, = 182; non-invasive weaning, = 182) were randomised. Groups were well matched at baseline. There was no difference between the invasive weaning and non-invasive weaning groups in median time to liberation from ventilation {invasive weaning 108 hours [interquartile range (IQR) 57-351 hours] vs. non-invasive weaning 104.3 hours [IQR 34.5-297 hours]; hazard ratio 1.1, 95% confidence interval [CI] 0.89 to 1.39; = 0.352}. There was also no difference in mortality between groups at any time point. Patients in the non-invasive weaning group had fewer IMV days [invasive weaning 4 days (IQR 2-11 days) vs. non-invasive weaning 1 day (IQR 0-7 days); adjusted mean difference -3.1 days, 95% CI -5.75 to -0.51 days]. In addition, fewer non-invasive weaning patients required antibiotics for a respiratory infection [odds ratio (OR) 0.60, 95% CI 0.41 to 1.00; = 0.048]. A higher proportion of non-invasive weaning patients required reintubation than those in the invasive weaning group (OR 2.00, 95% CI 1.27 to 3.24). The within-trial economic evaluation showed that NIV was associated with a lower net cost and a higher net effect, and was dominant in health economic terms. The probability that NIV was cost-effective was estimated at 0.58 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year.
CONCLUSIONS
A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation. However, patients who underwent non-invasive weaning had fewer days requiring IMV and required fewer antibiotics for respiratory infections.
FUTURE WORK
In patients who fail a SBT, which factors predict an adverse outcome (reintubation, tracheostomy, death) if extubated and weaned using NIV?
TRIAL REGISTRATION
Current Controlled Trials ISRCTN15635197.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 48. See the NIHR Journals Library website for further project information
Foot care in Epidermolysis bullosa: Evidence-based Guideline.
No full textTo provide service providers and users with an evidence-based set of current best practice guidelines for people and their families and carers, living with Epidermolysis bullosa (EB). A systematic literature review relating to the podiatric care of patients with EB was undertaken. Search terms were used, for which the most recent articles relating to podiatric treatment were identified as early as 1979 to present day, across seven electronic search engines: Medline, Wiley online library, Google Scholar, Athens, Researchgate, Net and pubfacts.com. The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used. The first guideline draft was analysed and discussed by clinical experts, methodologists and patients and their representatives at four panel meetings. The resulting document went through an external review process by a panel of experts, other health care professionals, patient representatives and lay reviewers. The final document will be piloted in three different centres in United Kingdom and Australia. Following an EB community international survey the outcomes indicated six main areas which the community indicated as a priority to foot management. These included blistering and wound management; exploring the most suitable footwear and hosiery for EB; management of dystrophic nails; hyperkeratosis (callus); maintaining mobility; and fusion of toes (pseudosyndactyly). Evidence here is limited but several interventions currently practised by podiatrists show positive outcomes. This article is protected by copyright. All rights reserved
Advances in the understanding of headache in idiopathic intracranial hypertension.
No full textPURPOSE OF REVIEW
To review the most relevant developments in the understanding of headache in idiopathic intracranial hypertension (IIH).
RECENT FINDINGS
The phenotype of the typical IIH headache is diverging from the historical thinking of a raised intracranial pressure headache, with the majority being classified as having migraine. A larger proportion of those with IIH have a past medical history of migraine, compared with the general population, highlighting the importance of re-examining those who have a change or escalation in their headache. The mechanisms underlying headache in IIH are not understood. Additionally, factors which confer a poor headache prognosis are not established. It is clear, however, that headache has a detrimental effect on all aspects of the patient's quality of life and is currently ranked highly as a research priority by IIH patients to better understand the pathophysiology of headache in IIH and identification of potential headache specific therapeutic agents.
SUMMARY
Headache remains the predominate morbidity in the majority of those with IIH. Headache management is an unmet need in IIH and future studies are required to investigate the probable complex mechanisms, as well as effective management
Violet-Blue Light Arrays at 405nm Exert Enhanced Antimicrobial Activity for Photodisinfection of Monomicrobial Nosocomial Related Biofilms.
No full textLight-emitting diodes (LEDs) demonstrate therapeutic effects for a range of biomedical applications including photodisinfection. Specific wavelength bands (centred at 405nm) are reported to be the most antimicrobial, however there remains no consensus on most effective irradiation parameters for optimal photodisinfection. The aim of this study was to assess decontamination efficiency by direct photodisinfection of monomicrobial biofilms using single (SWA), and multi wavelength (MWA) violet-blue light (VBL) arrays.Mature biofilms of nosocomial bacteria (, , and s) were grown on 96 well polypropylene PCR plates. The biofilms were then exposed to VBL for 2700 seconds (SWA) and 1170s (MWA), to deliver 0-670J/cm and the antibacterial activity of VBL assessed by comparing the seeding of the irradiated and non-irradiated biofilms. Non -irradiated groups were used as controls. VBL arrays were characterised optically (spectral irradiance and beam profile), and thermally.The SWA delivered 401nm VBL and the MWA delivered between 379 nm and 452nm albeit at different irradiances and beam profiles. In both arrays, irradiated groups were exposed to increased temperatures compared to non-irradiated controls. All bacterial isolates were susceptible to VBL and demonstrated reductions in seeding of exposed biofilms compared with non-irradiated controls. VBL at 405nm exerted the most antimicrobial activity, exhibiting reductions in seeding of up to 94%.Decontamination efficiency is dependent on irradiation parameters, bacterial species and strain, and experimental conditions. Controlled experiments that ameliorate heating effects and improve optical properties are required to optimise dosing parameters to advance successful clinical translation of this technology. This study reports the efficacy of VBL and BL, and its antimicrobial activity against mature biofilms of a range of important nosocomial pathogens. Whilst this study investigates the antibacterial activity of a range of wavelengths between 375-450nm, and identifies a specific wavelength region (∼405nm) with increased antibacterial activity, decontamination was dependent on bacterial species, strain, irradiation parameters and experimental conditions. Further research with controlled experiments that ameliorate heating effects, and improve optical properties are required to optimise dosing parameters to advance successful clinical translation of this technology
The potential of visible blue light (405 nm) as a novel decontamination strategy for carbapenemase-producing enterobacteriaceae (CPE).
No full textBackground
Carbapenemase-producing (CPE) pose a considerable threat to modern medicine. New treatment options and methods to limit spread need to be investigated. Blue light (BL) is intrinsically antimicrobial, and we have previously demonstrated significant antimicrobial effects on biofilms of a panel of isolates, including two CPEs.This study was performed to assess the antibacterial activity of 405 nm BL against a panel of CPE isolates (four encoding , three , two , and three encoding both NDM and OXA-48 carbapenemases).
Methods
In vitro experiments were conducted on 72 h old biofilms of CPEs which were exposed to 60 mW/cm of BL. Changes to biofilm seeding were assessed by measuring the optical density of treated and untreated biofilms.
Results
Twelve bacterial clinical isolates (comprising eight , one , and three ) were tested. BL was delivered for 5, 15 and 30 min, achieving doses of 162, 54, and 108 J/cm, respectively.All of the CPEs were susceptible to BL treatment, with increasing reductions in seeding with increasing durations of exposure. At 30 min, reductions in biofilm seeding of ≥80% were observed for 11 of the 12 isolates, compared to five of 12 after 15 min. CPE_8180 was less susceptible than the rest, with a maximum reduction in seeding of 66% at 30 min.
Conclusions
BL is effective at reducing the seeding of mature CPE biofilms in vitro, and offers great promise as a topical decontamination/treatment agent for both clinical and environmental applications
Repeated adrenaline doses and survival from an out-of-hospital cardiac arrest.
No full textBACKGROUND
Adrenaline is the primary drug of choice for resuscitation from out-of-hospital cardiac arrest (OHCA). Although adrenaline may increase the chance of achieving return of spontaneous circulation (ROSC), there is limited evidence that repeated doses of adrenaline improves overall survival, and increasing evidence of a detrimental effect on neurological function in survivors. This paper reports the relationship between repeated doses of adrenaline and survival in a cohort of patients attended by the London Ambulance Service in the United Kingdom.
METHODS
A retrospective review of OHCA treated by the London Ambulance Service over a one year period. Patients aged ≥18 years who received one or more doses of adrenaline (1 mg bolus) during resuscitation were included in the analyses. Outcomes described are survival to hospital discharge and survival to one year post-arrest.
RESULTS
Over the one year study period, 3151 patients received adrenaline during OHCA. A significant inverse relationship was found between increasing cumulative doses of adrenaline and survival both to hospital discharge and one year post-arrest. No patients survived after receiving more than ten adrenaline doses.
CONCLUSION
Our study indicates that repeated doses of adrenaline are associated with decreasing odds of survival. There were no survivors amongst patients requiring more than 10 doses of adrenaline
Metabolic Effects of Testosterone Therapy in Men with Type 2 Diabetes and Metabolic Syndrome.
No full textINTRODUCTION
Up to 40% of men with type 2 diabetes (T2DM) and metabolic syndrome (MetS) have hypogonadotrophic hypogonadism (HH). Men with HH are at increased risk of cardiovascular (CV) and all-cause mortality, as well as of the development of incident T2DM.
AIM
To review the current literature on the metabolic effects of testosterone therapy (TTh) in men with T2DM and MetS.
METHODS
We searched MEDLINE, Embase, and Cochrane Reviews for articles on T2DM, HH, testosterone deficiency, and CV and all-cause mortality published between May 2005 and July 2018, yielding 1817 articles, including 54 clinical trials and 32 randomized controlled trials (RCTs).
MAIN OUTCOME MEASURES
The main outcomes were glycemic control, insulin resistance, lipid profile, and metabolic markers associated with increased CV risk.
RESULTS
RCTs of TTh suggest significant benefits for sexual function, quality of life, glycemic control, insulin sensitivity, anemia, bone density, and fat and lean muscle mass that might be expected to translate into reduced long-term morbidity and mortality. Several longitudinal and observational studies suggest long-term sustained improvements in metabolic parameters and a trend toward reduced CV and all-cause mortality, especially in men at increased CV risk, such as those with T2DM and MetS. The greatest benefit is seen in those men treated with TTh to target levels and for longer durations.
CONCLUSION
Meta-analyses of RCTs, rather than providing clarification, may have further confused the issue by including underpowered studies of inadequate duration, multiple therapy regimens, some obsolete or withdrawn, and built-in bias in terms of studies included or excluded from analysis. Hackett G. Metabolic Effects of Testosterone Therapy in Men with Type 2 Diabetes and Metabolic Syndrome. Sex Med Rev 2019;XX:XXX-XXX
Insights for Care: The Healthcare Utilisation and Cost Impact of Managing Type 2 Diabetes-Associated Microvascular Complications.
No full textINTRODUCTION
The increasing prevalence of type 2 diabetes (T2DM) in the UK imposes a significant burden on the National Health Service (NHS). Despite the availability of effective treatments, the loss of glycaemic control over time results in significant comorbidities, including nephropathy, neuropathy and retinopathy. The cost of treating these microvascular complications has not been well documented, and this study aimed to provide an accurate assessment of the healthcare resource utilisation (HCRU) associated with managing T2DM and its complications.
METHODS
This retrospective cohort study utilised electronic medical records from patients with T2DM from the Heart of England Foundation Trust (HEFT), which captures data from patients using secondary care services. Patients were diagnosed with microvascular complications based on ICD-10 or OPCS codes. HCRU over a 2-year period was based on NHS Tariffs for healthcare services for inpatient, accident and emergency, and dialysis clinic usage.
RESULTS
The study cohort comprised 26,629 patients with T2DM who used HEFT services during the study period, 22.6%, 20.8% and 3.1% of whom had comorbid nephropathy, retinopathy or neuropathy, respectively. While the prevalence of diabetes in the overall HEFT population was reported to be 7% in 2012, diabetes and its associated complications accounted for more than 30% of secondary care costs. Furthermore, while patients with diabetes represent only 17% of HEFT inpatients, they account for more than 20% of service usage. The economic burden of microvascular complications increased substantially with the severity of the condition, with the overall cost exceeding £70 million over the 2-year period.
CONCLUSION
This study of patients with T2DM in a typical secondary care provider in the UK showed that avoiding the progression of microvascular complications could provide substantial cost savings through targeted interventions that improve outcomes and lower resource use.
FUNDING
Merck Sharp & Dohme Limited
Split versus living-related adult liver transplantation: a systematic review and meta-analysis.
No full textBACKGROUND-OBJECTIVE
The outcomes of split liver transplantation between recipients of deceased donor split liver transplant (SLT) or live donor liver transplants (LDLT) have never been compared in meta-analysis. It is important to understand graft and recipient survival between recipients of these grafts.
METHODS
Databases were searched for relevant articles over the previous 20 years (MEDLINE, Embase, Cochrane Library and Google Scholar). Meta-analyses were performed using both fixed- and random-effects models. Patient survival and graft survival were obtained using the inverse variance hazard ratio method.
RESULTS
There were differences in the characteristics of the donors and recipients. Donors of the SLT were younger compared to LDLT cohort [mean difference (MD) = - 11.12 years (- 15.41 to - 6.84), p < 0.001] whilst recipients of LDLT were younger [MD = - 2.06 years (- 1.12 to - 3.01), p < 0.001]. Significantly fewer men received grafts after SLT, 45%, compared to those receiving LDLT, 55%, [OR = 0.66 (0.55 to 0.80), p < 0.001]. There were no significant differences detected in postoperative complications, graft and patient 1-, 3- and 5-year survival between the SLT and LDLT cohorts.
CONCLUSIONS
There is no apparent difference in overall survival, graft survival or complications between recipients of SLT or LDLT. However, characteristics of the donor and recipients differed suggesting the need for adequate risk-adjusted assessment of outcomes