Comparison of Cystatin C and Creatinine in the Assessment of Measured Kidney Function during Critical Illness.

BACKGROUND: Incomplete recovery of kidney function is an important adverse outcome in survivors of critical illness. However, unlike eGFR creatinine, eGFR cystatin C is not confounded by muscle loss and may improve identification of persistent kidney dysfunction. METHODS: To assess kidney function during prolonged critical illness, we enrolled 38 mechanically ventilated patients with an expected length of stay of >72 hours near admission to intensive care unit (ICU) in a single academic medical center. We assessed sequential kidney function using creatinine, cystatin C, and iohexol clearance measurements. The primary outcome was difference between eGFR creatinine and eGFR cystatin C at ICU discharge using Bayesian regression modeling. We simultaneously measured muscle mass by ultrasound of the rectus femoris to assess the confounding effect on serum creatinine generation. RESULTS: Longer length of ICU stay was associated with greater difference between eGFR creatinine and eGFR cystatin C at a predicted rate of 2 ml/min per 1.73 m 2 per day (95% confidence interval [CI], 1 to 2). By ICU discharge, the posterior mean difference between creatinine and cystatin C eGFR was 33 ml/min per 1.73 m 2 (95% credible interval [CrI], 24 to 42). In 27 patients with iohexol clearance measured close to ICU discharge, eGFR creatinine was on average two-fold greater than the iohexol gold standard, and posterior mean difference was 59 ml/min per 1.73 m 2 (95% CrI, 49 to 69). The posterior mean for eGFR cystatin C suggested a 22 ml/min per 1.73 m 2 (95% CrI, 13 to 31) overestimation of measured GFR. Each day in ICU resulted in a predicted 2% (95% CI, 1% to 3%) decrease in muscle area. Change in creatinine-to-cystatin C ratio showed good longitudinal, repeated measures correlation with muscle loss, R =0.61 (95% CI, 0.50 to 0.72). CONCLUSIONS: eGFR creatinine systematically overestimated kidney function after prolonged critical illness. Cystatin C better estimated true kidney function because it seemed unaffected by the muscle loss from prolonged critical illness. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Skeletal Muscle Wasting and Renal Dysfunction After Critical Illness Trauma - Outcomes Study (KRATOS), NCT03736005 .

Distance and Socieoeconomic Status as Barriers to Cochlear Implantation.

OBJECTIVE: To assess the distance burden for access to cochlear implant (CI)-related services and to assess whether socioeconomic disadvantage or level of education and occupation influenced uptake of CIs. STUDY DESIGN: Retrospective case review. SETTING: A CI services provider operating across multiple centers. PATIENTS: All patients undergoing CI surgery in a 2-year period between March 2018 and February 2020. INTERVENTIONS: Diagnosis of hearing loss, CI surgery, and subsequent habilitation and mapping. MAIN OUTCOME MEASURES: Distance traveled by patients to their audiological diagnostic, CI surgery hospital, and habilitation sites; subjects' index of relative socioeconomic advantage and disadvantage (IRSAD) and index of education and occupation (IEO). RESULTS: n = 201 children and n = 623 adults. There was a significant difference across IRSAD domains for children (p < 0.0001) and adults (p < 0.0001), and IEO in children (p = 0.015) and adults (p < 0.0001) when tested for equal proportions. The median driving distance from home to the diagnostic audiological site for children was 20 km (mean, 69 km; range, 1-1184 km; upper quartile, 79 km; lower quartile, 8 km). There was no significant difference between the driving distances from home to the CI surgery hospital site, or the mapping/habilitation sites between children and adults. There was no correlation for age at first surgery and either IRSAD/IEO. CONCLUSIONS: The burden of distance for access to CI in Australia is significant for the upper quartile who may not live within the large city centers. Greater consideration needs to be given regarding barriers to CI for those in lower socioeconomic and educational groups to ensure equity of access across different socioeconomic and educational level backgrounds.

Effectiveness of prone position in spontaneously breathing patients with COVID-19: A prospective cohort study.

We present a single centre study describing the effect of awake prone position (PP) on oxygenation and clinical outcomes in spontaneously breathing patients with novel coronavirus disease (COVID-19). Between 1st March and 30th April 2020, forty eight of 138 patients managed outside of the critical care unit with facemask oxygen, high flow nasal oxygen (HFNO) or continuous positive airway pressure (CPAP), underwent PP. Prone position was associated with significant improvement in oxygenation, lower ICU admission, tracheal intubation, and shorter ICU length of stay. Lack of response to PP may be an indicator of treatment failure, requiring early escalation.

Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study.

BACKGROUND: A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic. METHODS: We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021. RESULTS: The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740-5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066-2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587-3 100 808) up to December 31, 2021. CONCLUSIONS: The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.

Emergency hospital admissions associated with non-communicable diseases 1998-2018 in England, Wales and Scotland: an ecological study.

BACKGROUND: Non-communicable diseases (NCDs) are increasingly prevalent and were responsible for 40.5 million deaths (71%) globally in 2016. We examined the number of NCD-related emergency hospital admissions during the years 1998 to 2018 in the UK. METHODS: Demographic features for those admitted as an emergency with NCDs as their primary diagnosis were collated for all admissions in England, Wales and Scotland. NCDs recorded as secondary diagnoses for all admissions in England from 2012 to 2018 were additionally recorded. RESULTS: We identified 120,662,155 emergency episodes of care. From 1998 to 2018 there was an increase from 1,416,233 to 1,892,501 in annual emergency admissions due to NCDs. This, however, represented a fall in the proportion of NCD among all emergency admissions, from 33.4% to 26.9%. Mean age of all patients admitted increased from 46.3 to 53.8 years. CONCLUSION: Despite a fall in proportion of NCD admissions, the population acutely admitted to hospital was increasingly elderly and increasingly comorbid.

The incidence and associations of acute kidney injury in trauma patients admitted to critical care: A systematic review and meta-analysis.

BACKGROUND: As more patients are surviving the initial effects of traumatic injury clinicians are faced with managing the systemic complications of severe tissue injury. Of these, acute kidney injury (AKI) may be a sentinel complication contributing to adverse outcomes. OBJECTIVE: To establish the incidence of AKI in patients admitted to critical care after major trauma, to explore any risk factors and to evaluate the association of AKI with outcomes. DATA SOURCES: Systematic search of MEDLINE, Excerpta Medica database and Cochrane library from January 2004 to April 2018. STUDY SELECTION: Studies of adult major trauma patients admitted to critical care that applied consensus AKI criteria (risk injury failure loss end stage [RIFLE], AKI network, or kidney disease improving global outcomes) and reported clinical outcomes were assessed (PROSPERO Registration: CRD42017056781). Of the 35 full-text articles selected from the screening, 17 (48.6%) studies were included. DATA EXTRACTION AND SYNTHESIS: We followed the PRISMA guidelines and study quality was assessed using the Newcastle-Ottawa score. The pooled incidence of AKI and relative risk of death were estimated using random-effects models. MAIN OUTCOMES AND MEASURES: Incidence of AKI was the primary outcome. The secondary outcome was study-defined mortality. RESULTS: We included 17 articles describing AKI outcomes in 24,267 trauma patients. The pooled incidence of AKI was 20.4% (95% confidence interval [CI], 16.5-24.9). Twelve studies reported the breakdown of stages of AKI with 55.7% of patients classified as RIFLE-R or stage 1, 30.3% as RIFLE-I or stage 2, and 14.0% as RIFLE-F or stage 3. The pooled relative risk of death with AKI compared was 3.6 (95% CI, 2.4-5.3). In addition, there was a concordant increase in odds of death among six studies that adjusted for multiple variables (adjusted odds ratio, 2.7; 95% CI, 1.9-3.8; p = <0.01). CONCLUSION: Acute kidney injury is common after major trauma and associated with increased mortality. Future research is warranted to reduce the potential for harm associated with this subtype of AKI. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level III.

A systematic review and meta-analysis of return to work after mild Traumatic brain injury.

OBJECTIVE: To perform a systematic review and meta-analysis of return to work (RTW) times for adult patients with mild traumatic brain injury (mTBI). METHODS: Six databases and six trials registries were searched. Inclusion: studies reporting RTW, > 30 patients, adults, with mTBI. Exclusion: final measurement RTW < 30 days after injury, first measurement > 1 year. RESULTS: Of 978 records, 14 eligible studies were identified. Two included patients exclusively in paid employment pre-injury; four included paid employment, students, homemakers or other activities; seven included pre-injury occupational status described but unclear; one included patients whose pre-injury occupational status not described. Three reported average RTW, 12 reported proportions of patients RTW at pre-specified time-points (1 both). Average RTW times varied from 13 to 93 days. At 1 month the proportion of patients RTW (three pooled studies) was 0.56 (95% CI 0.30-0.79), at 6 months (six studies) 0.83 (0.74-0.89), at 12 months (seven studies) 0.89 (0.83-0.93). CONCLUSION: More than half of patients with mTBI have returned to work by 1 month after injury, and more than 80% by 6 months. Most studies had poor internal validity. Reporting of outcomes in mTBI is variable, and this accounted for some of the heterogeneity found in this review.

The Academic Surgical Collaborative: A three-year review of a trainee research collaborative.

INTRODUCTION: The Academic Surgical Collaborative (ASC) is a trainee research collaborative (TRC) formed in the UK in October 2014. Three years on, the achievements are presented along with advice for emerging and established TRCs. Methods: A retrospective review of internal, member-maintained ASC records was conducted. Membership numbers, PubMed indexed publications, presentations and prizes awarded were all calculated over time. Google Scholar was used to calculate citations per ASC publication. An online survey was distributed to members to ascertain member satisfaction. RESULTS: With 62 active members (predominantly medical students) the ASC has published 33 PubMed indexed papers over three years, with a mean of 21 citations per paper (SD 89, range 0-491). 54 presentations have been delivered and eight prizes have been awarded for ASC research projects. 60% of ASC members believe the ASC delivers research that improves patient care. Key learning points for the ASC have been the use of a set of resources distributed to new members, the value of regular meetings, close mentoring throughout research projects to develop the skills of junior researchers, encouragement for junior members to present at conferences, and an ongoing focus on research conduct and improving evidence based medicine. CONCLUSIONS: The ASC has fulfilled many of its goals set out at its inception. The ASCs subsequent aims are to enhance existing research training for junior members, advances in the field of core outcome development and also multi-collaborative research.

Compliance of systematic reviews in ophthalmology with the PRISMA statement.

BACKGROUND: Systematic reviews and meta-analyses are becoming increasingly important methods to summarize published research. Studies of ophthalmology may present additional challenges because of their potentially complex study designs. The aim of this study was to evaluate the reporting quality of systematic reviews and meta-analyses on topics in ophthalmology to determine compliance with the PRISMA guidelines. We assessed articles published between 2010 and 2015 in the five major relevant journals with the highest impact factors. METHODS: The MEDLINE and EMBASE databases were searched to identify systematic reviews published between January 2010 and December 2015 in the following 5 major ophthalmology journals: Progress in Retinal and Eye Research, Ophthalmology, Archives of Ophthalmology, American Journal of Ophthalmology, and Survey of Ophthalmology. The screening, identification, and scoring of articles were independently performed by two teams, and the results were submitted to statistical analysis to determine medians, ranges, and 95% CIs. RESULTS: A total of 115 articles were included. The median compliance was 15 out of 27 items (56%), the range was 5-26 (26-96%), and the inter-quartile range was 10 (37%). Compliance was highest in items related to the 'description of rationale' (item 3, 100%) and sequentially lower in 'the general interpretation of results' (item 26, 96%) and 'the inclusion of a structured summary in the abstract' (item 2, 90%). Compliance was poorest in the items 'indication of review protocol and registration' (item 5, 9%), 'specification of risk of biases that may affect the cumulative evidence' (item 15, 24%), and 'description of clear objectives in the introduction' (item 4, 26%). CONCLUSION: The reporting quality of systematic reviews and meta-analyses in ophthalmology should be significantly improved. While we recommend the use of the PRISMA criteria as a guideline before journal submission, additional research aimed at identifying potential barriers to compliance may be required to improve compliance with PRISMA guidelines.

How to get shortlisted for medical jobs.

Progressing up the medical career ladder is a tough business. Most medical and surgical applications center the requirement for a holistic, balanced individual. As a result, there are usually specific marking criteria in predefined sections. This article provides a guide into what employers are looking for and how best to build your portfolio in these areas.

How to conduct a clinical audit and quality improvement project.

Audits and quality improvement projects are vital aspects of clinical governance and continual service improvement in medicine. In this article we describe the process of clinical audit and quality improvement project. Guidance is also provided on how to design an effective audit and bypass barriers encountered during the process.

Why apply for an intercalated research degree?

Intercalated degrees are commonly undertaken as part of the medical undergraduate course. In this article, we discuss the advantages and disadvantages of intercalation, along with alternatives that could be considered.

A study of the effect of sorbitol on osmotic tolerance during partial desiccation of bovine sperm.

The goal of the study was to improve the partial desiccation survival of bovine sperm by decreasing the dehydration induced osmotic injury. The protective role of sorbitol, a polyol, was investigated by (i) studying the osmotic behavior of sperm in hypertonic Tyrode's buffer in the presence of sorbitol and trehalose, (ii) studying the effect of sorbitol and trehalose on sperm motility following partial dehydration. The osmotic behavior studies included the assessment of motility and volumetric responses in the presence of the additives. For the drying experiments, motility was assayed after drying the samples to different end water content followed by immediate rehydration. Compared to the effect of "intracellular+extracellular" trehalose alone, results showed a much improved motility in the presence of sorbitol and trehalose. While the drying results suggest an enhanced osmotolerance in the presence of sorbitol, the study of motility under hypertonic conditions combined with the sperm volume excursion experiments suggest that sorbitol imparts the enhancement by permeating into the cell cytoplasm.

Vitrification by ultra-fast cooling at a low concentration of cryoprotectants in a quartz micro-capillary: a study using murine embryonic stem cells.

Conventional cryopreservation protocols for slow-freezing or vitrification involve cell injury due to ice formation/cell dehydration or toxicity of high cryoprotectant (CPA) concentrations, respectively. In this study, we developed a novel cryopreservation technique to achieve ultra-fast cooling rates using a quartz micro-capillary (QMC). The QMC enabled vitrification of murine embryonic stem (ES) cells using an intracellular cryoprotectant concentration in the range used for slowing freezing (1-2M). The cryoprotectants used included 2M 1,2-propanediol (PROH, cell membrane permeable) and 0.5M extracellular trehalose (cell membrane impermeable). More than 70% of the murine ES cells post-vitrification attached with respect to non-frozen control cells, and the proliferation rates of the two groups were similar. Preservation of undifferentiated properties of the pluripotent murine ES cells post-vitrification cryopreservation was verified using three different types of assays: the expression of transcription factor Oct-4, the presentation of the membrane surface glycoprotein SSEA-1, and the elevated expression of the intracellular enzyme alkaline phosphatase. These results indicate that vitrification at a low concentration (2M) of intracellular cryoprotectants is a viable and effective approach for the cryopreservation of murine embryonic stem cells.

Desiccation kinetics and biothermodynamics of glass forming trehalose solutions in thin films.

In this study, the desiccation kinetics of aqueous trehalose solutions were investigated numerically by solving the coupled heat and mass transfer problem with a moving interface using the finite element method. The free volume models for vapor pressure and mutual diffusion coefficient were incorporated into the model to account for the effect of glass transition on the heat and mass transport process that ultimately determines the desiccation kinetics. It was found that the temperature in the film could drop significantly upon the initiation of drying due to the absorption of latent heat associated with water evaporation although the spatial distribution of temperature in the solution is very homogeneous. On the contrary, the spatial distribution of water content in the solution is non-homogeneous, particularly at the solution-vapor interface where an extremely thin layer of skin with extremely low molecular mobility usually forms during drying. The solution film can be dried to approximately 6-10 wt.% residual water within minutes for thin films; but drying times depends strongly on the initial film thickness, initial solution concentration, temperature, and convective coefficient. Desiccation to below 6 wt.% residual water is very slow due to the retarded water mobility in the extremely thin skin where the solution is in the glassy state. Since the water mobility in a trehalose solution or glass with 6-10% residual water is still high enough to allow degradative reactions to occur in a relatively short time at room temperature, it is important that the samples should be kept at a temperature around 0 degrees C or lower for storage after drying. Furthermore, approaches that might enable further quick reduction of the residual water to less than 6-10 wt.% are also proposed so that a sample could be preserved at super-zero or even room temperature. The established models and the reported results will be useful for the development of effective protocols for lyopreservation of biomaterials including living cells using trehalose as the excipient.

Forced and natural convective drying of trehalose/water thin films: implication in the desiccation preservation of Mammalian cells.

Trehalose is believed to offer desiccation protection to mammalian cells by forming stable glassy matrices. The goal of the current study was to explore the desiccation kinetics of thin films of trehalose-water solution under forced and natural convective conditions and to investigate the thermophysical state of mammalian cells at the bottom of the thin film. We developed a finite difference model based on the mass and energy conservation equations coupled to the water transport model from the cells. The boundary conditions were obtained from correlations or experimental measurements and the Gordon-Taylor equation was used to predict the glass transition temperature at every location. Results indicated that there are three distinct regimes for drying for both forced and natural convection, characterized by the slope of the moisture content plot as a function of time. Our results also indicate that the surface of the solution reached the glassy state in less than 10 min for the Reynolds (forced) numbers explored and approximately 30 min for some Rayleigh (natural convective) numbers; however, significant water was trapped at this instant. Larger drying force hastened quicker glass formation but trapped more water. The numerical model was capable of predicting the drying kinetics for the dilute region accurately, but deviated while predicting the other regimes. Based on these experimental validations of the model, the osmotic response of different cells located at the bottom of the solution with orders of magnitude difference in their membrane permeability (Lp) was predicted. The results suggested that extracellular glass formed around cells at the bottom of a trehalose-water solution by the propagation of glass into the solution; however it takes more than an order of magnitude time (approximately 7 min to >100 min for forced convective drying) to remove sufficient water to form glass around cells from the time when the first surface glass is formed. This is attributed to low diffusivity of water through the glass. In addition, the water transport from the glassy matrix could be either diffusion or Lp limited. For diffusion-limited transport, lowering the film thickness at the beginning of drying by half almost lowers the drying time by an order of magnitude. In summary, the optimal design of convective desiccation protocols requires accounting for the size of the cell, their membrane permeability (Lp) and the starting thickness of the solution.

Thermal characterization of Nakagata's mouse sperm freezing protocol.

This paper reports the results of an experimental study of the warming and cooling rates achieved using the popular Nakagata Protocol for murine sperm cryopreservation. Problems with the storage and maintenance of the huge number of genetically engineered mouse strains have led to an increased need for murine sperm preservation. Recent studies have begun to focus on optimizing the cryopreservation of murine sperm by carefully studying the effects of cooling and warming rates on sperm survival. In current practice, however, the Nakagata protocol is widely used. The actual cooling and warming rates achieved using the Nakagata protocol have not previously been determined; and the Nakagata protocol has a number of unspecified parameters which we have found can significantly affect cooling rates, warming rates and sperm survival. A detailed study of the thermal response of samples frozen and thawed using the Nakagata protocol reveals that the cooling rates range from 30 to almost 300 degrees C per minute depending on the exact manner in which the Nakagata protocol is implemented. Warming rates range from 160 degrees C/min to about 1000 degrees C/min. Sperm survival depended significantly on the particular cooling rate achieved, and less strongly on the warming rates. Overall, it was found that the particular manner in which the Nakagata protocol was implemented could strongly affect cooling rates and sperm survival; and, consistent with the findings of Mazur and Koshimoto, an optimal cooling rate appears to exist in the range of cooling rates that can be achieved using the Nakagata protocol.